Stem cells

Definition

Stem cells are cells which have not yet developed a special structure and function but which have the capacity to mature into cells with the characteristic shapes and specified functions of other cells in the body, such as heart, skin, muscle and nerve cells. Such cells are microscopic in size and can be found in all multi-cellular organisms.

Embryonic stem cells stained blue as seen under a microscope. Credit: Nissim Benvenisty, Wikimedia.

Importance

Stem cells were first used for bone marrow transplants (BMTs), a proceedure that was introduced as a treatment for cancer and genetic blood disorders in the 1960s. Every year stem cells are presently used in about 60,000 BMT operations worldwide. This procedure is increasingly using stem cells sourced from peripheral and umbilical cord blood rather than from the bone marrow. Stem cells are not only vital for BMTs but are being explored for their power to replace or even heal damaged tissues and cells in the body. They have proven particularly valuable for bone grafts. The value of stem cells for bone grafts is expected to be worth US$600 million by 2015. Stem cells have also been approved in Canada and South Korea for the treatment of acute myocardial infarction (heart attack), anal fistula and for cartilage injury and oesteoarthritis. Such cells are additionally used as coatings for synthetic organs produced in the laboratory. A coating with stem cells provides a means to prevent implant rejection. Since 2008 eight patients have successfully received transplants of artificially created windpipes coated with stem cells. The tracheas were made by growing the patient's stem cells on a laboratory-made scaffold. Such an approach is expected to be used in the future creation of other organs such as a replacement oesophagus, heart valve, diaphragm, kidney, or lung. In 2011 the stem cell market was valued at about US$2 billion. Most of this consisted of revenue from BMTs. Syed and Evans predict that the stem cell therapeutics market will be generating US$8.8 billion by 2016. This includes stem cell therapies, stem cell banking and stem cell ancillary products (Nature Reviews Drug Discovery 12, March 2013, 185-6).

Discovery

The concept of a stem cell was first proposed by researchers working on embryonic development in the nineteenth century. They saw such cells as the starting point for biological processes. From the early twentieth century stem cells began to be seen as the source of different kinds of blood cells. Yet, blood stem cells could not be visualised in this period, so many doubted their existence. Knowledge advanced during the Second World War through the identification of a recovery factor in bone marrow which was thought to help regenerate the blood system. This was discovered by the haematologists William Bloom and Leon Jacobson as part of their research into the effects of radiation on the blood system which they carried out as part of the Manhattan Project to build the first atom bomb. It was this observation that laid the basis for the development of the BMT procedure for the treatment of blood cancer (leukaemia). BMTs opened the way to the identification and characterisation of stem cells within the bone marrow in the 1960s. In 1978 stem cells were also discovered to be present in human cord blood and three years later scientists cultivated the first embryonic stem cells from mice blastocysts.

Application

Stem cells are currently used as research tools to understand the signals and mechanism of cell differentiation. This is useful not only for understanding the cause of disease, but also for the development of new therapies. The ability to generate large numbers of specialised cells from stem cells has also led to their use for testing the safety of new medicines, thereby reducing the need for animal testing. Cancer stem cells, for example, are used to screen potential anti-tumour drugs. Stem cells are also being explored for their properties to replace cells lost in degenerative diseases and for repairing cells in damaged tissues, a field known as regenerative medicine. Today more than 1,100 clinical studies, the overwhelming majority of them using adult stem cells, are being conducted to investigate the power of stem cell therapy. This includes treatments for retinal diseases, neurological conditions such as Parkinson's and Alzheimer's disease, heart disease such as post-ischaemic stroke, and type 1 diabetes.

Stem cells: timeline of key events

The stem cell is conceived as a distinctive cell which serves as the starting point for blood formation.1882-01-01T00:00:00+0000The key difficulty is that the blood stem cell cannot be identified using microscopy1890-01-01T00:00:00+0000The Russian histologist Alexander Maksimov proposes the term 'stem cell' for scientific usage.1908-01-01T00:00:00+0000McLaren was a major pioneer in the development of IVF. She was also the key architect behind the Human Embryology and Fertilisation Act (1990) which provided the world’s first legal guidelines for infertility treatment and all human embryo research. Following this Act, McLaren served for 10 years on the Human Fertility and Embryology Authority, established in 1991, and became a critical player in debates about the governance of embryonic stem cells for therapy. She also made history in 1991 by becoming the Royal Society’s first woman officer. 1927-04-26T00:00:00+0000Research undertaken by Health Division of Manhattan Project. 1942-01-01T00:00:00+0000Observation made by Leon O. Jacobson working within Health Division of the Manhattan Project.1942-01-01T00:00:00+0000The atomic age brings new radiation dangers. Understanding these dangers in order to safeguard against them becomes an important focus of post-war radiobiology. 1945-01-01T00:00:00+0000Set up in Harwell, UK, the role of the AERE is to undertake research that serves the whole of Britain's nuclear enterprise, including the dangers of radiation.1945-01-01T00:00:00+0000The MRC RU is an autonomous institute that forms part of the AERE Harwell, UK.1947-01-01T00:00:00+0000The objective of these experiments is to understand how the bone marrow protects against radiation damage.1949-01-01T00:00:00+0000Schoemaker was co-founder and first Chief Executive Officer of Centocor, an American biotechnology company that pioneered the commercialisation of monoclonal antibody diagnostics and therapeutics. After Centocor was sold to Johnson & Johnson for $5.2 billion in 1999, Schoemaker founded Neuronyx to develop cellular therapies. One of the treatments pioneered by Neuronyx was the use of stem cells from bone marrow to help regenerate heart tissue damaged by heart attacks. 1950-03-23T00:00:00+00001951-01-01T00:00:00+0000Conceived by Egon Lorenz, the experiment was designed to test whether - like the spleen - marrow can regenerate the blood system. This experiment sets the foundation for bone marrow transplantation. 1951-01-01T00:00:00+0000The experiments involve bone marrow transplants from mice where the donor marrow cells are marked with a specific chromosome marker, T6. The presence of the T6 marker in all blood cells of surviving recipient mice indicates their blood system was regenerated by a cell from the donor. This empirical evidence lends support to the concept of the blood stem cell.1956-01-01T00:00:00+0000Lays the basis for improving the treatment of leukaemia in humans.1956-01-01T00:00:00+0000The transplant was carried out by Edward Donall Thomas at the Mary Imogene Basset Hospital in New York, which was affiliated to Cornell University. Thomas gave the treatment to a patient with leukaemia. It involved using high doses of total-body irradiation to wipe out the cancer and then infusing marrow cells from an identical twin. While the transplant was initially successful, the patient died later from a recurrence of leukaemia. The achievement was published in ED Thomas, HL Lochte, WC Lu, JW Ferrebee, 'Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy'. The New England Journal of Medicine, 257 (J.W. (12 September 1957), 491–6.1957-09-12T00:00:00+0000The patients are 6 Yugoslav physicians who had been accidentally irradiated at a nuclear power plant.1959-01-01T00:00:00+0000Each sick child was terminally ill and chemotherapy was of no further use. Lethal levels of radiation were used to try to eradicate the leukaemia, followed by the infusion of genetically identical marrow (from the healthy twin).1959-01-01T00:00:00+00001959-01-01T00:00:00+0000Severity of GvHD in humans unforeseen, and seemingly insurmountable 1960-01-01T00:00:00+0000This discovery sets the stage for all current research on adult and embryonic stem cells.1961-01-01T00:00:00+0000Researchers return to animal models.1962-01-01T00:00:00+00001962-01-01T00:00:00+0000Transplant conducted by George Mathe at the Institute of Cancer and Immunotherapeutics, Paul-Brouse Hospital, Paris. The procedure focuses on genetically different patient and donor. 1965-01-01T00:00:00+0000Stem cells gain increasing interest for the recovery of the blood system in patients undergoing chemotherapy and bone marrow transplants1965-01-01T00:00:00+0000The Institute is based in Manchester, UK1965-01-01T00:00:00+0000The cultivation is on solid (agar) media in petri dishes. This marks a major methodological advance as marrow is difficult to grow in the laboratory.1965-01-01T00:00:00+0000The proceedure was performed by physician-scientist Robert Good to treat boy born with severe combined immunodeficiency. 1968-01-01T00:00:00+0000The tumour stem cell idea emerges from the study of teratomas in tumour biology. Teratomas are a group of tumours, some benign and some malignant. Such tumours develop from cells early in their development before they become muscle cell, or a nerve cell, etc. 1969-01-01T00:00:00+0000 Bone marrow cells remain difficult to grow in the laboratory. Marrow regeneration in the irradiated/transplanted mouse remains the strongest evidence for its existence, and for its presence in marrow.1970-01-01T00:00:00+0000Ronald Cape, Peter Farley and Donald Glaser establish Cetus Corporation to generate industrial micro-organisms for the production of greater amounts of chemical feedstocks, antibiotics and vaccine compounds. 1971-01-01T00:00:00+0000The transplant was carried out by Richard O'Reilly and Robert Good. This lays the foundation for the routine use of bone marrow transplants for treating some blood cancers. Such transplants are classed as immunotherapy because immune cells from the donor kill cancer cells in the recipient. 1973-01-01T00:00:00+00001975-01-01T00:00:00+0000First long-term clinical study of bone marrow transplants in over 100 terminally ill acute leukaemia patients in whom chemotherapy was of no further use reports the survival of thirteen patients. This marks a breakthrough in leukaemia therapy, and sets the scene for the use of bone marrow transplants as a routine therapeutic option for some patients with some forms of acute leukaemia.1977-01-01T00:00:00+00001978-01-01T00:00:00+0000The identity of the blood stem cell, especially that in the human, and even its existence remains the subject of debate because the cell is difficult to isolate. Those involved in the debate include the Manchester group (Dexter, Lord) and American groups (Weissmann and Morrison). Part of the problem is that techniques for studying the human blood stem cell lagged behind that of animal models. 1980-01-01T00:00:00+0000The technique was developed by Martin Evans and Matt Kaufman. They showed that by delaying implantation it was possible to obtain slightly enlarged mouse blastocysts and that cells taken from these blastocysts could be used to establish mouse embryo stem cell cultures. The work was published in MJ Evans, MH Kaufman, 'Establishment in culture of pluripotential cells from mouse embryos', Nature, 292/154 (1981), 154-56.1981-07-09T00:00:00+0000The advantage of the method was that it avoided in vivo alteration. It involved culturing cells isolated from blastocysts in a medium that contains a factor to stimulate embryonic stem cell proliferation or suppress their differentiation. The method was developed by Gail Martin. It was published in G R Martin, 'Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells', PNAS USA, 78/12 (1981) 7634-81981-12-01T00:00:00+0000Work commences on the cancer stem cell theory as an explanation for leukaemia, and as an explanation for remission in this form of cancer. 1982-01-01T00:00:00+00001982-01-01T00:00:00+0000The progenitor cells are biological cells that, like stem cells, have the capacity to differentiate into a specific type of cell. The distinction between marrow and progenitor cells is made by measuring the regenerative capacity in vivo of the cells using colony methods. 1982-01-01T00:00:00+0000The company is a public company1982-01-01T00:00:00+0000Identified by Curt Civin and his team at Johns Hopkins, the subset of cells bearing the CD34 (surface) marker is shown also to contain other kinds of cell. The research shows that the blood stem cell can be enriched for, but not purified. The advance proves useful in the clinical setting where enrichment for the CD34 cell can aid faster recovery of the blood system in patients undergoing chemotherapy and/or bone marrow transplants for serious blood disorders. 1984-01-01T00:00:00+00001984-01-01T00:00:00+00001984-01-01T00:00:00+00001984-01-01T00:00:00+00001986-01-01T00:00:00+00001987-01-01T00:00:00+0000The company is a public company1987-01-01T00:00:00+0000Blood stem cells from the umbilical cord are understood, theoretically, to be both especially potent and unlikely to provoke a strong immunological response in the recipient. 1988-01-01T00:00:00+0000The company is a public company1988-01-01T00:00:00+0000 GJ Spangrude, S Heimfeld, IL Weissman, 'Purification and characterization of mouse hematopoietic stem cells', Science, 241 (1988), 58-62. 1988-07-01T00:00:00+00001989-01-01T00:00:00+0000The aim is to supply blood cells/bone marrow for transplantation.1990-01-01T00:00:00+0000Discovered by Urban Lendahl.1990-01-01T00:00:00+00001990-01-01T00:00:00+0000This supplies blood cord from siblings to treat childhood Fanconi anaemia. 1992-01-01T00:00:00+00001992-01-01T00:00:00+00001992-01-01T00:00:00+0000Procedure devised by Claudio Bordignon at Vita-Salute San Raffaele University, Milan. 1992-01-01T00:00:00+0000This is accomplished through the generation of embryonic stem cell-derived mice.1993-01-01T00:00:00+00001994-01-01T00:00:00+00001994-01-01T00:00:00+0000This is put forward by John Dick and his colleagues who theorise about the existence of the leukaemia stem cell in acute and chronic myeloid leukaemia. 1994-01-01T00:00:00+0000A. Ramon-cueto, M. Nieto-Sampedro, Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glia transplants, Exp Neurol, 27/2 (1994), 232–44.1994-06-01T00:00:00+00001995-01-01T00:00:00+0000The belief that adult stem cells, especially the blood stem cell, can give rise to cells such as brain, liver and cardiac gives rise to notion that adult stem cells could be used like embryonic counterparts for regenerative therapies, helping in degenerative diseases of the brain and heart. This marks a paradigm shift as it goes against dogma from decades of research and clinical success with the blood stem cell. 1996-01-01T00:00:00+0000Research conducted by KA Smale et al at Queen's University (Canada), Y. Li et al at University College London, T Imaizumi et al at Yale Univbersity School of Medicine, Guntinas-Lichius et al at the University of Cologne, H H Nash et al the Uniformed Services University of the Health Sciences, M J Ruitenberg et al at the Netherlands Institute for Brain Research.1996-01-01T00:00:00+0000This overturns the long-held belief that the brain is unable to generate new neurons.1998-01-01T00:00:00+0000James Thomson, Jeffrey Jones, and co-workers reported isolating five human embryonic stem cell lines from human blastocysts (Science 282/5391 (1998), 1145-7).1998-10-06T00:00:00+0000Identified by Jonas Frisen and colleagues1999-01-01T00:00:00+0000Founded by Hubert Schoemaker, Neuronyx aimed develop stem cell technology to treat neurological disorders such as multiple sclerosis, Alzheimer's disease, Parkinson's disease, and brain cancer. 1999-01-01T00:00:00+0000Identified by Jonas Frisen and colleagues2000-01-01T00:00:00+00002000-01-01T00:00:00+0000Songtao Shi and colleagues at the National Institutes of Health discovered stem cells in the pulp found in the centre of extracted adult wisdom teeth. S Gronthos et al, 'Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo', PNAS, 97/25 (2000), 13625-30. 2000-12-05T00:00:00+0000This is the first collaborative stem cell research network2001-01-01T00:00:00+00002001-01-01T00:00:00+0000The creation of new embryonic stem cell lines is banned.2001-08-09T00:00:00+0000Advanced Cell Technology, a private lab, created a six-cell embryo by removing DNA from a human egg and injecting it with the DNA of a skin cell. The aim was to produce genetically matched replacement cells for patients with a wide range of diseases.2001-10-01T00:00:00+0000The ISCF is set up to foster international collaboration and promote global good practices and accelerating progress in biomedical science.2002-01-01T00:00:00+0000The multipotent cells are a specialised cell type produced from pluripotent stem cells. The purified multipotent marrow stem cells are shown capable of being used as single injected cells for extended marrow regeneration in vivo.2002-01-01T00:00:00+0000Guidelines included a ban on public funding of research that could lead to cloning, as well as a ban on creating embryos simply for research purposes. It also banned payments to obtain embryos for research.2002-03-04T00:00:00+0000S.K. Singh et al., 'Identification of a cancer stem cell in human brain tumors', Cancer Research, 63/18 (2003), 5821-8.2003-01-01T00:00:00+0000Dolly the sheep was created by cloning an adult cell. This was done by transferring the nucleus of an adult sheep's cell to the nucleus of an unfertilised egg cell. It took 277 attempts to achieve success.2003-02-14T00:00:00+0000Stem cells from baby teeth found to behave much like stem cells harvested from umbilical cord blood. The discovery was made by Songtao Shi, a paediatric dentist, and his colleagues at the US National Institutes of Health. It was made on the basis of investigating baby teeth collected from both Shi's six-year old daughter and her friends. The stem cells were isolated by extracting pulp from the teeth and culturing the cells for several days. A typical incisor tooth was found to have 12 to 20 stem cells. The work was published in M M Miura et al, 'SHED: Stem cells from human exfoliated deciduous teeth', PNAS, 100/10 (2003), 5807-12.2003-05-13T00:00:00+0000Dopaminergic cells believed to hold promise for treating Parkinson's disease.2004-01-01T00:00:00+0000ICSCN's aim is to unify international efforts to make stem cell therapy a reality for a broad range of debilitating diseases.2004-01-01T00:00:00+0000James Till and Ernest McCulloch awarded the Lasker Prize for experiments that first established a technique - the spleen colony assay - for enumerating the blood stem cell and studying its regenerative effects. Setting the stage for the contemporary development of stem cell biology. 2005-01-01T00:00:00+00002005-01-01T00:00:00+0000The Pattison report sets out plans and investment for the emerging paradigm of regenerative medicine where both embryonic and adult somatic stem cells will be important players. 2005-01-01T00:00:00+0000Andras Nagy created embryonic stem cell lines from donated embryos no longer needed by couples undergoing fertility treatment. This laid the foundation for the creation of embryonic stem cells from human skin four years later. 2005-06-15T00:00:00+0000A team at Harvard Stem Cell Institute reported fusing adult skin cells with embryonic stem cells to reset the culture so that the cells behave like embryonic stem cells. The researchers did the work using pelvic bone cells as the somatic cells and a different human embryonic cell line. Chad A Cowan, Jocelyn Alenza, Douglas A Melton, Kevin Eggan, 'Nuclear reprogramming of somatic cells after fusion with human embryonic stem cells', Science, 309/5739 (2005), 1369-73. 2005-08-25T00:00:00+00002006-01-01T00:00:00+0000Schoemaker was a Dutch biochemist who was co-founder and first Chief Executive Officer of Centocor, an American biotechnology company that pioneered the commercialisation of monoclonal antibody diagnostics and therapeutics. After Centocor was sold to Johnson & Johnson for $5.2 billion in 1999, Schoemaker founded Neuronyx to develop cellular therapies. One of the treatments pioneered by Neuronyx was the use of stem cells from bone marrow to help regenerate heart tissue damaged by heart attacks. 2006-01-01T00:00:00+0000A team lead by Robert Lanza at Advanced Cell Technology, a biotechnology company in Worcester, Massacusettes, announced the creation of a six-cell embryo by removing DNA from a human egg and injecting it with the DNA of a skin cell. The aim was to produce genetically matched replacement cells for patients with a wide range of diseases. The work was published in Y. Chung et al, 'Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres', Nature, 439 (2006), 216–19.2006-01-12T00:00:00+0000Japanese researcher Shinya Yamanaka shows that only four particular genes are required to create induced pluripotent stem cells, laying the foundation for reprogramming existing cells to create stem cells without using human embryos.2006-06-01T00:00:00+00002006-11-16T00:00:00+0000The Prize was awarded to to Mario Capecchi, Martin Evans and Oliver Smithies. Their work made it possible to modify specoific genes in the germline of mammals which could produce offspring that carried and expressed the modified gene. Their method is commonly called knockout technology. This has given scientists the means to study the role of specific genes in development, physiology and pathology. 2007-01-01T00:00:00+00002007-01-01T00:00:00+00002007-01-01T00:00:00+0000U.S. researchers isolated stem cells from amniotic fluid and placental tissue left over from routine prenatal tests used to detect foetal abnormalities. The amniotic fluid stem cells have characteristics of both human embryonic stem cells and adult stem cells. But they do not form tumours when implanted in lab animals, as embryonic cells can do. P De Coppi, et al, 'Isolation of amniotic stem cell lines with potential for therapy', Nature Biotechnology, 25/1 (200&, 100-6.2007-01-07T00:00:00+0000The patient, Timothy Ray Brown, had been living with virus since 1995. Known initially only as 'the Berlin Patient', Timothy received blood-forming stem cells to halt his cancer from a donor who carried a mutation known to confer natural resistance to HIV. The treatment was conceived by Gero Hütter at Free University of Berlin Brown stopped taking antiviral drugs just before given the stem cells. Remaining free of HIV for the rest of his life, Brown's case helped spur NIH to fund further research into the use of stem cell transplants to cure HIV. 2007-02-16T00:00:00+00002007-04-27T00:00:00+0000Two different groups demonstrated through experiments in mice that normal skin cells could be reprogrammed to an embryonic state. Prior to this embryonic stem cells were created by implanting DNA into an egg, which would then grow to provide a supply of stem cells. This earlier technique involved the destruction of a viable embryo. The scientists found the trick was to add four genes to a somatic cell's existing complement of DNA. These genes code for a set of proteins that prompt the cell to exhibit embryonic properties. The research was carried out by Shinya Yamanaka at Kyoto University and James Thomson at the University of Wisconsin-Madison. 2007-06-06T00:00:00+0000McLaren was a major pioneer in the development of IVF. She was also the key architect behind the Human Embryology and Fertilisation Act (1990) which provided the world’s first legal guidelines for infertility treatment and all human embryo research. Following this Act, McLaren served for 10 years on the Human Fertility and Embryology Authority, established in 1991, and became a critical player in debates about the governance of embryonic stem cells for therapy. She also made history in 1991 by becoming the Royal Society’s first woman officer. 2007-07-07T00:00:00+0000The Human Fertilisation and Embryology Authority allowed for the fusion of human-animal embryos, also known as chimeras, to create stem cells. 2007-09-05T00:00:00+0000Japanese researchers Shinya Yamanaka and Kazutoshi Takahashi reported the generation of pluripotent stem cells from mature human fibroblasts. Their technique opened the possibility of producing stem cells from almost any other human cell. They published their method in K Takahashi, K Tanabe, M Onnuki, et al 'Induction of pluripotent stem cells from adult human fibroblasts by defined factors', Cell, 131/5 (2007), 861-72.2007-11-30T00:00:00+00002008-01-01T00:00:00+0000A team of scientists led by George Q Daley at the Harvard Stem Cell Institute reported the creation of stem cells for 10 genetic disorders that will enable researchers to watch diseases develop in a lab dish. The researchers used ordinary skin cells and bone marrow from people with a variety of diseases, including Parkinson's, Huntington's and Down syndrome to produce the stem cells. They published their results in I H Park, et al, 'Disease-specific induced pluripotent stem cells', Cell, 134/5 (2008), 877-86.2008-09-05T00:00:00+00002009-01-01T00:00:00+00002009-01-01T00:00:00+0000Study published reporting that transplanting stem cells from the lining of the spinal cord reverses paralysis associated with spinal cord injuries in animal tests. The transplanted cells regenerated 10 times faster in animals with spinal cord injuries than in healthy animals. V. Moreno-Manzano et al, 'Activated Spinal Cord Ependymal Stem Cells Rescue Neurological Function', Stem Cells, 27 (2008), 733-43, DOI: 10.1002/stem.242009-01-28T00:00:00+0000An HIV patient in Berlin who had leukaemia was given a stem cell transplant with cells taken from a donor with a mutation in the CCR5 gene. The gene encodes a receptor that HIV uses to enter immune cells (CD4 T cells). The research was published in G Hutter, New England Journal of Medicine, 360, (2009), 692–98.2009-02-11T00:00:00+0000Canadian researchers report in Nature the generation of embryonic-like stem cells from adult human tissue, arguing the process could eventually cure diseases like spinal cord injuries and Parkinson's.2009-03-01T00:00:00+0000Obama's order cleared the way for federal funding of research using embryonic stem cells. This expanded the number of stem cell lines available to researchers from 20 to about 700.2009-03-09T00:00:00+0000Meta-analysis of prospective trials with 6007 patients showed stem cell transplants improved the survival rates of people with acute myeloid leukaemia (the most common form of acute leukaemia) and advocated the use of stem cell transplants become a standard treatment for some patients. J. Koreth et al, 'Allogeneic stem cell transplantation for acute myeloid leukemia in first complete remission: systematic review and meta-analysis of prospective clinical trials', JAMA, 301/22 (2009), 349-61. 2009-06-10T00:00:00+00002010-01-01T00:00:00+00002010-01-01T00:00:00+0000L Warren, PD Manos, T Ahfeldt, T et al (5 Nov 2010) 'Highly efficient reprogramming to pluripotency and directed differentiation of human cells with synthetic modified mRNA', Cell Stem Cell, 7/5, 618-30.2010-11-05T00:00:00+00002011-01-01T00:00:00+0000Allers, K, Hutter, G, Hofmann, J, Loddenkemper, C, Rieger, K, Thiel, E, et al,'Evidence for the cure of HIV infection by CCR5?32/?32 stem cell transplantation', Blood, 117/10, (2011): 2791–99.2011-03-10T00:00:00+0000US Court of Appeals for the District of Columbia lifted a lower-court injunction, opening the way to resume federal funding of research on embryonic stem cells.2011-04-29T00:00:00+0000The first patient to receive the therapy was Sue Freeman, a 78 year old, diagnosed with AMD. The study, approved by the FDA, was designed to test the treatment's safety, not its effectiveness. The therapy involved injecting retinal cells derived from embryonic stem cells into the eyes of patients suffering from dry age-related macular degeneration (AMD) and Stargardt’s macular dystrophy, leading causes of blindness in the elderly and children, respectively. 2011-07-14T00:00:00+00002012-01-01T00:00:00+0000The study used induced pluripotent stem cells in six patient with advanced AMD. 2014-01-01T00:00:00+0000Scientists at the University of Nottingham led by Kevin Shakesheff announced the development of a new stem cell micro-environment which allows for the self-renewal of cells and their evolution into cardiomyocyte (heart) cells. The new technique opened up new avenues for exploring the development of stem cells for therapy. The work was published in J E Dixon, D A Shah, et al, 'Combined hydrogels that switch human pluripotent stem cells from self-renewal to differentiation', PNAS, 111/15 (2014), 5580-85, DOI: 10.1073/pnas.1319685111.2014-03-31T00:00:00+0000Researchers at the Institute for Regenerative Medicine, University of Pennsylvania, reported the generation of stem cells by putting the nucelus of an adult skin cell inside an egg that went through the initial stages of embryonic development. YG Chung, JH Eum, JE Lee, SH Shim, V Sepilian, S W Hong, Y Lee, NR Treff, Y H Choi, EA Kimbrel, R Dittman, R Lonza, DR Lee, 'Human Somatic Cell Nuclear Transfer Using Adult Cells', Cell Stem Cell, 14/6 (2014), 777-80.2014-06-05T00:00:00+0000Paralysed patient able to walk after his spinal cord was treated with olifactory ensheathing cells, specialist cells that aid the sense of smell, taken from his nose. The treatment was developed by Geoff Raisman and colleagues at University College London's Institute of Neurology together with Pawel Tabakow at Wroclaw Medical University. The research was supported by the Nicholls Spinal Injury Foundation and the UK Stem Cell Foundation. 2014-10-21T00:00:00+0000The operation was carried out at Moorfield Eye Hospital, London. It involved transplanting eye cells, called retinal pigment epithelieum, which were derived from stem cells. The surgery was performed by Lyndon Da Cruz as part of the London Project to Cure Blindness, a collaboration between Moorfields, the UCL Institute of Optahalmology and the National Institute for Health Research. 2015-09-29T00:00:00+0000Trial aimed at assessing the use of stem cells, grown from donated human bone marrow, to slow down or stop tissue damage in kidneys in diabetic patients. The project is led by Timothy O'Brien from the National University of Ireland and funded by 6 million Euro grant from European Union Horizon 2020 programme. 2015-10-20T00:00:00+0000The research was conducted by scientists at the University of Warwick who studied tissue samples donated by 183 patients at the Imlantation Research Clinic in Coventry. The finding opened up new possibilities for developing stem cell based treatments for the prevention of miscarriage. E. S. Lucas et al, 'Loss of endometrial plasticity in recurrent pregnancy loss', Stem Cells, 34/2 (2016), 346-56. 2016-03-08T00:00:00+0000The infants received the therapy to regenerate healthy lenses in their eyes as part of a small scale trial carried out by Kang Zhang and his team at the Shiley Institute of the University of California in San Diego, together with colleagues in China. The study was published in H. Lin et al, 'Lens regeneration using endogenous stem cells with gain of visual function', Nature, 531 (2016), 323-28.2016-03-09T00:00:00+0000The cells proved capable of differentiating into many cell types, such as nerve, heart, and pancreatic cells, while retaining a single set of chromosomes. It is hoped the cells could help reduce the compexity of identifying genetic abnormalities. The work was done by Dieter Egli of Columbia University, New York, and Nissim Benvenisty, Hebrew University, Jerusalem. It was published in I. Sagi et al, 'Derivation and differentiation of haploid human embryonic stem cells', Nature (2016), doi:10.1038/nature17408.2016-03-17T00:00:00+0000The Karolinksa Institute sacked Paolo Macchiarini for continuing to use his new method in operations even though it showed little or no sign of working. 2016-03-23T00:00:00+0000The procedure, tried out in clinical trials, involved the injection of modified human, adult stem cells from bone marrow directly taken from two donors into the brains of 18 chronic stroke patients. The trials were led by Gary Steinberg at Stanford University School of Medicine. The 18 patients were selected for treatment from 379 patients. Most had suffered a stroke a year before treatment, and had damage to their motor function. Twelve of the patients were treated at Stanford the remaining six were treated at the University of Pittsburgh. A number of the patients previously confined to wheelchairs were able to walk after receiving the treatment. Many of the patients sustained their improvements for more than one year and some for two years. 2016-06-02T00:00:00+0000Stem cells injected into 11 patients undergoing bypass surgery shown to reduce the size of scarred tissue by 40 per cent. K Anatasiadis, et al, Journal of Cardiovascular Translational Research, 9/3 (June 2016), 202-13.2016-07-24T00:00:00+0000PA Muraro, M Pasquini, HL Atkins, et al, 'Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis', JAMA Neurolology, 20 Feb 2018, doi:10.1001/jamaneurol.2016.58672017-02-20T00:00:00+0000Patient treated with lentiviral vector-mediated addition of a gene into autologous hematopoietic stem cells. JA Ribell, S Hacien-Bey-Abina, E. OPayen, A. Magnani, et al, 'Gene therapy in a patient with sickle cell disease', NEJM, 376 (2017), 848-55.2017-03-02T00:00:00+0000S. Ellys Harrison, B. Sozen, N. Christodoulou, C. Kyprianou, M. Zernicka-Goetz, 'Assembly of embryonic and extra-embryonic stem cells to mimic embryogenesis in vitro', Science, DOI: 10.1126/science.aal1810 2017-03-03T00:00:00+0000M. Mandai et al, 'Autologous Induced Stem-Cell–Derived Retinal Cells for Macular Degeneration', NEJM, 376 (2017), 1038-46.2017-03-16T00:00:00+0000The women went blind as a result of the treatment. A.E. Kuriyan et al, 'Vision Loss after Intravitreal Injection of Autologous “Stem Cells” for AMD', NEJM, 376 (2017), 1047-53. 2017-03-16T00:00:00+0000G. Fontana, J. Gershlak, M. Adamski, J-S Lee, S. Matsumoto, H. D. Le, B. Binder, J. Wirth, G. Gaudette, W. L. Murphy, 'Decellularized Plants: Biofunctionalized Plants as Diverse Biomaterials for Human Cell Culture', Advanced Healthcare Materials, DOI: 10.1002/adhm.2017700382017-04-19T00:00:00+0000Total of 17 boys treated in clinical trial, of which 15 showed marked improvement. Treatment used a modified form of HIV as the vector for infusing corrective genes to generate glial cells. F. Eichler, C. Duncan etl al, 'Hematopoietic Stem-Cell Gene Therapy for Cerebral Adrenoleukodystrophy', NEJM, DOI: 10.1056/NEJMoa17005542017-10-04T00:00:00+0000CTJ van Velthoven, A de Morree, I M Enger, J O Brett, T A Rando, 'Transcriptional Profiling of Quiescent Muscle Stem Cells In Vivo', Cell Reports, 21/1 (2017), 1994-2004. 2017-11-14T00:00:00+0000Douglas Waters, an 86 year old patient at Moorfields Eye Hospital in London gained improved eyesight in his right eye after having stem cells inserted underneath the rods and cones in the back of his eye. The stem cells were grown in a patch and were designed to provide new retinal pigment epithelium. While the patient's eyesight was not completely restored, he gained a renewed ability to read the newspaper. Another patient with the same condition who received the same treatment also experienced some improvements to her eyesight. Both patients, who were taking part in a phase I trial, maintained improved vision for a year after the treatment. The results were published in L da Cruz, K Fynes, O Georgiadis et al, 'Phase 1 clinical study of an embryonic stem cell–derived retinal pigment epithelium patch in age-related macular degeneration', Nature Biotechnology, 36 (2018) 328-37. 2018-03-19T00:00:00+0000A team of managed to reprogramme the skin cells into dendritic cells. These immune cells search the body's tissues for foreign particles, such as bacteria, viruses or cancer cells, and devour them. The team identified three essential proteins (PU.1, IRF8 and BATF3) that are required to transform the the skin cells into dendritic cells. The process takes only 9 days and opens the possibility of developing novel dendritic cell-based immunotherapies against cancer. The research was published in FF Rosa et al, 'Direct reprogramming of fibroblasts into antigen-presenting dendritic cells', Science Immunology, 3/30 (2018) eaau4292, DOI: 10.1126/sciimmunol.aau42922018-12-07T00:00:00+0000The patient received a stem-cell transplant that replaced their white blood cells with HIV-resistant versions. The cells were taken from a donor who had two copies of a mutation in the CCR5 gene that confers resistance to HIV infection. The CCR5 gene codes for a receptor on white blood cells involved in the body's immune response. HIV normally binds to these receptors and attacks the cell. By removing the gene the receptors stop working normally. The patient was given the treatment as part of therapy for blood cancer. He was able to stop taking antiretroviral drugs after 16 months, and 18 months later had no sign of the virus. The research was published in RK Gupta, et al, Nature (2019), DOI 10.1038/s41586-019-1027-42019-03-05T00:00:00+0000Developed by a team of researchers led by Brian Sorrentino at St. Jude Children’s Research Hospital, the gene therapy was given to eight infants. The treatment involved collecting bone marrow from the patients and then using the lentiviral vector to insert a correct copy of the IL2RG gene into the genome of patients’ blood stem cells. The research was published in E Momcartz, et al, 'Lentiviral Gene Therapy Combined with Low-Dose Busulfan in Infants with SCID-X1', New England Journal of Medicine, 380: (2019): 1525-34, 2019-04-19T00:00:00+0000
Date Event People Places
1882Concept of the stem cell is put forward for the first timeHaeckel, Dantchakoff, Pappenheim, Ehrlich, MaximowUniversity of Jena, Charite Hospital, Koch Institute, Petrograd University
1890 - 1930Debate begins over whether one stem cell provides supply of new cells for the entire blood system or if there is a different stem cell for each constituent cell lineage of the blood system Bloom, MaximowUniversity of Chicago, Petrograd University
1908The term 'stem cell' is coinedMaximovPetrograd University
26 Apr 1927Anne McLaren was born in London, UKMcLarenUniversity College London, Edinburgh University, Cambridge University
1942 - 1945Animal experiments launched to investigate the biological effects of acute and chronic exposure to different forms and intensities of ionising radiationJacobson, Zirkle, Bloom University of Chicago
1942 - 1945One part of the blood system, the spleen, offers some form of protection against radiation damageJacobsonUniversity of Chicago
1945Research continues into the damaging effects of ionising radiation upon the blood system - the tissue most sensitive to radiation effectsJacobson, LorenzUniversity of Chicago, National Cancer Institute, MRC RRU
1945Atomic Energy Research Establishment (AERE) foundedAERE
1947Medical Research Council Radiobiological Unit (MRC RU) establishedLoutit, Ford, BarnesMRC RRU
1949First experiments transplanting spleen from non-radiated mice into radiated miceJacobson, Marks, GastonUniversity of Chicago
23 Mar 1950Hubert Schoemaker was born in Deventer, The NetherlandsSchoemakerDeventer, The Netherlands
1951 - 1956Debate about whether the 'recovery factor' present in the spleen and marrow is a hormone or a cellJacobson, Lorenz, Loutit, CongdonUniversity of Chicago, National Cancer Institute, MRC RRU
1951Transfer of marrow into lethally irradiated mice shows that marrow, like spleen, is regenerativeLorenz, Congdon, UphoffNational Cancer Institute
1956Experiments with mice confirm radiation recovery factor is a distinctive cellLoutit, Ford, Barnes, HamertonMRC RRU
1956Mice with leukaemia treated successfully with lethal radiation followed by bone marrow transplantLoutit, Barnes MRC RRU
12 Sep 1957First report of successful bone marrow transplants performed in human patientsThomas, Lochte, Lu, FerrebeeBassett Medical Center, Cornell University
1959Infused allogeneic bone marrow in accidentally irradiated workers shown to give rise to mature blood cellsMatheHopital Saint Louis
1959Bone marrow transplants in two sets of identical twin girls fails to eradicate leukaemiaThomas, Ferrebee, Sahler Bassett Medical Center
1959Experiments in mice prove the existence of resident blood stem cells in marrowThomas Bassett Medical Center
1960Bone marrow transplants being undermined by immunological reactions (especially graft-versus-host-disease (GvHD))ThomasBassett Medical Center
1961Existence and properties of transplantable stem cells in mouse bone marrow established and the first methodology for counting them is devisedJames, Till, McCulloch, Siminovitch, Becker, Wu, FowleOntario Cancer Institute
1962 - 1965Bone marrow transplants in humans abandoned by Thomas group due to graft-versus-host-diseaseThomas Bassett Medical Center
1962Nuclei from adult frog cells reprogrammed to full embryonic potential after transfer into frog eggsGurdon, AltmanCambridge University
1965First successful allogeneic marrow transplant reported in patient with leukaemiaMatheInstitute of Cancer and Immunotherapeutics
1965Distinctive and powerfully regenerative cell resident in bone marrow, known from now on as stem cells 
1965Paterson Institute for Cancer Research established as a major centre for blood stem cell researchLajtha, Schofield, Lord, Dexter, PatersonPaterson Institute for Cancer Research, Christie Cancer Hosptial
1965Development of a technique for the in vitro cultivation of bone marrow cellsMetcalf, Bradley, Sachs, PluznikQueen Elizabeth II Hospital, Weizmann Institute
1968First successful bone marrow transplant from a siblingGoodMemorial Sloan Kettering Cancer Center
1969Concept of the tumour stem cell is bornFialkow, Pierce, Hamburger, Salmon, Nowell, Damjanov, SolterUniversity of Washington in Seattle
1970Blood stem cell proves highly elusive as it is difficult to isolate and visualise 
1971Cetus Corporation, the first biotechnology was foundedCape, Farley, GlaserCetus
1973First successful bone marrow transplant from unrelated donorGood, O'ReillyMemorial Sloan Kettering Cancer Center
1975A liquid media is developed for growing bone marrow cells, including the blood stem cellDexterPaterson Institute for Cancer Research
1977Bone marrow transplants is clinically provenDonnallFred Hutchinson, Seattle, New York
1978Transplantable stem cells discovered in human cord bloodEvansCambridge University
1980 - 1990Existence of the blood stem cell contestedDexter, Lord, Weissmann, Morrison
9 Jul 1981Mouse embryonic stem cells first isolated and cultured in the laboratoryEvans, Kaufman, MartinCambridge University
December 1981Another method published for cultivating mouse embryonic stem cellsMartinUniversity of California San Francisco
1982Leukaemia emerges as a key means for understanding of the role of the stem cell in cancerDick, LapidotOntario Cancer Institute
1982Amcell, a private biotechnology company, is formed to commercialise blood stem cells 
1982Marrow stem cells shown to be distinct from progenitor cells  
1982AIS, the first biotechnology company to commercialise blood stem cell-based innovation is establishedAIS
1984A molecular marker, CD34, is identified as specific for a subset of marrow cells containing the blood stem cellCivinJohns Hopkins
1984 - 1996Ongoing litigation between CellPro and Baxter Healthcare Corporation over the use of the CD34 marker for cell separation technologyCellPro, Baxter Healthcare
1984CD34 marker used as the basis for cell separation technology 
1984Blood stem cells extensively purified for first time 
1986National Marrow Donor Programme established in US 
1987First clinical trials of foetal neural cell grafting in patients with Parkinson’s diseaseBjorklund, Lindvall Lund University
1987CellPro, the second biotechnology company is formed to commercialise blood stem cellsCellPro
1988First reported clinical use of umbilical cord bloodBroxmeyerIndiana University
1988SyStemix, the third biotechnology company is established to commercialise blood stem cellsSystemix
1 Jul 1988The first hematopoietic stem cells were isolated in miceSpangrude, Heimfeld, WeissmanStanford University
1989Aastrom, a private biotechnology company is formed to commercialise blood stem cells 
1990Some companies attempt, but do not succeed, to develop blood stem cell-based businessBaxter Healthcare
1990Discovery of the nesting gene, the most commonly used marker for neural stem cellsLendahlKarolinska Institutet
1990Mouse marrow regenerating stem cells are completely separated from in vivo colony-forming cells for first time 
1992First public bank set up for umbilical cord blood bank in New YorkRubinsteinNew York Blood Center
1992Neural stem cells identified in the adult human brain 
1992Progenitor, a private biotechnology company is formed to commercialise blood stem cells 
1992Stem cells used as vectors to deliver the genes needed to correct the genetic disorder SCIDBordignonVita-Salute San Raffaele University
1993Embryonic stem cells are proven to be pluripotent; having the ability to differentiate into different cell types 
1994First separation of cancer stem cells from the majority of cells in a cancer  
1994Patients with damaged corneas successfully treated with corneal stem cells  
1994Cancer stem cell theory advancedDickOntario Cancer Institute
1994Experiments in adult rats indicate olifactory ensheathing cells could regenerate injured dorsal root axons in spinal cordRamon-Cueto, Nieto-SampedroInstituto Cajal
1995First derivation of primate embryonic stem cell lines  
1996First reports that blood stem cell might be able to give rise to cells other than those of the blood systemBlau, Lagasse, Lemischka, Morrison, Thiese, Krause, Gussoni, Bjornson 
1996 - 2002Experiments with rats conducted by different research teams around the world confirm olifactory ensheathing cells help repair spinal cordSmale, Li, Imaizumi, Guntinas-Lichius, Nash, RuitenbergQueen's University, University College London, Yale University, University of Cologne, University of the Health Sciences, Netherlands Institute for Brain Research
1998Human brain demonstrated to contain cells with stem-like propertiesEriksson, GageSahlgrenska University Hospital, Salk Institute
October 1998First human embryonic stem cell line derived Thomson, Itskovitz-Eldor, Shapiro, Waknitz, Swiergiel, Marshall, JonesUniversity of Wisconsin-Madison
1999Adult neural stem cells identified as capable of forming new neural stem cellsFrisenKarolinska Institutet
1999Neuronyx foundedSchoemaker 
2000Adult stem cells recognised as having potential to generate variety of cells for other organsFrisenKarolinska Institutet
2000Retinal stem cells identified in mice  
5 Dec 2000Wisdom teeth demonstrated to be source of stem cellsShi, Gronthos, Mankani, Brahim, Gehron RobeyNIH
2001The Stem Cell Network is formed  
2001Dermal stem cells identified in adult skin tissue  
9 Aug 2001US places restricitions on embryonic stem cell research 
October 2001Human embryo cloned to make stem cellsAdvanced Cell Technology
2002International Society for Stem Cell Research (ISCF) established 
2002First complete purification of multipotent marrow stem cells from mice 
4 Mar 2002Canadian Institutes of Health Research unveiled guidelines for stem cell research 
2003Cancer stem cells isolated in human brain tumours Singh 
14 Feb 2003Dolly the sheep, the first cloned mammal, diedWilmutRoslin Institute
13 May 2003Dental pulp from baby teeth demonstrated to be source for stem cellsShi, Miura, Gronthos, Zhao, Lu, Fisher, Gehron Robey, NIH
2004First derivation of dopaminergic cells from human embryonic stem cells 
2004International Consortium of Stem Cell Networks (ICSCN) initiated 
2005Lasker Prize awarded to James Till and Ernest McCullochTill, McCulloch 
2005First evidence for human bone cancer stem cells  
2005UK Pattison Report emphasizes stem cells as likely potential therapies for the future 
15 Jun 2005Canadian researchers created the country's first embryonic stem cell linesNagySamuel Lunenfeld Research Institute
25 Aug 2005Harvard scientists reported reprogramming adult skin cells into embryonic stem cells Cowan, Eggan, Melton, AlienzaHarvard Stem Cell Institute
2006Normal mammary stem cells demonstrated in adult mice  
1 Jan 2006Hubert Schoemaker died in Philadelphia, USASchoemaker 
12 Jan 2006First successful cloning of human embryo to make stem cellsLanza, Chung, Klimanskaya, Becker, Marh, Lu, Johnson, MeisnerAdvanced Cell Technology
June 2006Four genes identified as important for reprogramming cellsYamanakaKyoto University
16 Nov 2006Stem cell injections reported to ease symptoms in muscular dystrophy in dogs 
2007Nobel Prize for Physiology for Medicine awarded for discoveries enabling germline gene modification in mice using embryonic stem cellsCapecchi, Evans, SmithiesUniversity of North Carolina, University of Utah
2007First physical identification and localization of mammalian intestinal stem cells  
2007First evidence for human colon cancer stem cells  
January 2007Scientists isolated new stem cell source in amniotic fluidDe Coppi, Bartsch, Siddiqui, Xu, Santos, Perin, Mostoslavsky, Serre, Snyder, Yoo, Furth, Soker, Atala 
February 2007Stem cell transplant used to treat leukaemia in a patient found to cure his HIVHütterFree University of Berlin
April 2007Canadian researchers converted normal human blood cells into leukaemia stem cells to investigate leukaemiaDick 
June 2007Skin cells reprogrammed to become like embryonic stem cellsYamanakaKyoto University, University of Wisconsin-Madison
7 Jul 2007Anne McLaren died McLarenUniversity College London, Edinburgh University, Cambridge University
5 Sep 2007British regulators approved human-animal embryo research 
30 Nov 2007Human cells reprogrammed to make pluripotent stem cellsYamanaka, TakahashiKyoto University
2008Gairdner Prize is awarded to Sam Weiss for the discovery of neural stem cellsWeiss 
5 Sep 2008Scientists created stem cells for 10 disordersDaley, Park, Arora, Huo, Maherall, Ahfedt, Shimamura, Lensch, Cowan, HochedlingerHarvard Stem Cell Institute
2009Lasker Prize awarded to John Gurdon and Shinya Yamanaka for discoveries in nuclear reprogramming. Yamanaka is also awarded the Gairdner PrizeGurdon, YamanakaCambridge University, Kyoto University
2009Induced pluripotent stem cells created with minimal residual genomic alteration  
January 2009First animal tests suggest stem cells may reverse paralysisMoreno-Manzano, Rodríguez-Jiménez, García-Roselló, Laínez, Erceg, Calvo, Ronaghi, Lloret, Planells-Cases,Sánchez-Puelles, Stojkovic,University of Valencia
11 Feb 2009Stem-cell transplant reported to be promising treatment for curing HIVHutterUniversity of Berlin
March 2009Embryonic like stem cells generated from adult human tissueNagy, WhiteMount Sinai Hospital, Toronto
9 Mar 2009U.S. President Barack Obama reversed restrictions on stem cell research imposed by former President George W. Bush 
10 Jun 2009Stem cell transplants reported to improve survival for leukaemia patientsKoreth, Schlen, Kopecky, Honda, Sierra, Djulbegovic, Wadleigh, DeAngelo, Stone, Sakamaki Appelbaum, Dohner, Antin, Soiffer, CutlerDana Farber Cancer Institute
2010Adult cells reprogrammed into neurons, cardiac muscle and blood cells  
2010First clinical trial of human embryonic-derived stem cells for treatment of spinal cord injury  
5 Nov 2010Modified mRNA reported to transform skin cells into pluripotent stem cellsLuigi Warren, Philip Manos, Ahfeldt, Ahfeldt, Yuin-Han Loh, Hu Li, Frank Lau, Wataru Ebina, Pankaj Mandal, Zachary Smith, Meissner, George Daley, Brack, James Collins, Chad Cowan, Schlaeger, RossiHarvard University
2011Isolation of multipotent human blood stem cells capable of forming all cells in the blood system  
10 Mar 2011Patient suffering from acute myeloid leukaemia is cured of HIV-1 after receiving bone marrow stem cells transplanted from donor with mutated CCR5 gene. This awakens interest in developing HIV treatment that renders a patient's cells resistant to HIV-1Allers, Hutter, Hofmann, Loddenkemper, RiegerCharite-University Medicine Berlin
April 2011US funding of embryonic stem cell research permitted 
14 Jul 2011First safety trial launched in humans to test embryonic stem cell therapy to treat blinding diseasesSchwartzUniversity of California Los Angeles
2012John Gurdon and Shinya Yamanaka win the Nobel Prize in Physiology or Medicine for the discovery that mature cells can be reprogrammed to become pluripotent stem cellsGurdon, YamanakaCambridge University, Kyoto University
2014Japanese scientists completed successful skin-to-eye stem cell transplant in a 70 year old patient with age-related macular degeneration, a blinding disease. 
March 2014Breakthrough for manufacturing stem cellsDixon, Shah, Rogers, Hall, Weston, Parmenter, McNally, Denning, ShakesheffUniversity of Nottingham
5 Jun 2014First embryonic stem cells cloned from a man's skinChung, Eum, Lee, Shim, Sepilian, Hong, Lee, Treff, Choi, Kimbrel, Dittman, LonzaUniversity of Pennsylvania
October 2014Stem cells taken from nose demonstrated to repair spinal cord injury Raisman, TabakowUniversity College London, Wroclaw Medical University
29 Sep 2015First UK patient recieved experimental stem cell treatment for age-related macular degeneration University College London, National Institute for Health Research
20 Oct 2015UK NHS sets up stem cell factory in Liverpool to supply experimental treatment for people with diabetes 
8 Mar 2016UK scientists link repeated miscarriages to a reduction of stem cells in lining of the wombBrosens, QuenbyUniversity of Warwick
9 Mar 2016A dozen infants born with cataracts reported to regain sight after receiving new stem cell therapyZhangUniversity of California San Diego
17 Mar 2016Scientists announce the first generation of an embryonic stem cell that carries a single copy of the human genome rather than the usual twoEgli, Benvinsty, Sagi, Chia, Golan-Lev, Peretz, Weissbein, Sui, Sauer, YanukkaColumbia University
23 Mar 2016Surgeon involved in world's first trachea transplant made from patient's own stem cells sacked for scientific misconductMacchiariniKarolinska Institute
2 Jun 2016Stem cells reported to provide substantial recovery in patients disabled by strokeSteinbergStanford University
24 Jul 2016Small-scale case study showed power of stem cells to repair damaged scar tissue caused by heart attacksAnastasiadis, Antonitsis, Westaby, Reginald, Sultan, Doumas, Efthimiadis, EvansAHEPA University Hospital, Oxford University, Cardiff University
20 Feb 2017Data published from 25 centres in 13 countries for 281 patients indicated autologous hematopoietic stem cell transplantation can halt the progression of MS disabilityMuraro, Pasquini, AtkinsImperial College
2 Mar 2017Gene therapy reported to successfully reverse sickle cell disease in first patientRibell, Hacien-Bey-Abina, Payen, Magnani, LeboulchUniversity of Paris
3 Mar 2017Cambridge scientists report the development of an aritificial mouse embryo using stem cellsUniversity of Cambridge
16 Mar 2017Study published showing a personalised treatment using a patient's own stem cells effective for treating macular degeneration, a common blinding diseaseMandaiRIKEN Center for Developmental Biology
16 Mar 2017Follow-up of three women given stem cell treatment in 2015 to treat macular degeneration raises concerns KuriyanFlaum Eye Institute
April 2017Researchers at University of Washington-Madison demonstrated the possibility of growing skin, bone marrow and blood vessels using plant scaffolds with stem cellsUniversity of Washington-Madison, Olbrich Botanical Gardens
4 Oct 2017Gene therapy shown in clinical trials to halt progression of adrenoleukodystrophy, a fatal brain disease inherited by boys Eichler, Duncan, WilliamsHarvard University, Bluebird Bio, Boston Children’s Hospital
14 Nov 2017Stem cells in the body found to have significantly different gene-expression profile than stem cells isolated and cultivated in the laboratory van Velthoven, de Morree, Enger, Brett, Rando, Stanford University
19 Mar 2018Stem cell treatment reported to be promising treatment for age-related macular degenerationda Cruz, Fynes, Georgiadis, Kerby, Luo, Ahmado, Vernon, CoffeyUniversity College London
7 Dec 2018Mouse and human skin cells reprogrammed into immune cells to fight cancerRosa, Pires, Kurtochkin, Ferreira, Gomes, Palma, Shaiv, Solanas, Azenha, Papatsenko, Schulz, Reis e Sousa, Carlos-Filipe Lund University, Skolkovo Institute of Science and Technology, Francis Crick Institute
5 Mar 2019Second patient reported free of HIV after receiving stem-cell therapyGuptaUniversity of Cambridge
19 Apr 2019Gene therapy shown to be promising in treating infants born with X-linked severe combined immunodeficiency (SCID-X1)Mamcarz, Zhou, Lockey, Abdelsamed, Cross, Kang, Ma, Condori, Dowdy, Triplett, Maron St. Jude Children’s Research Hospital

1882

Concept of the stem cell is put forward for the first time

1890 - 1930

Debate begins over whether one stem cell provides supply of new cells for the entire blood system or if there is a different stem cell for each constituent cell lineage of the blood system

1908

The term 'stem cell' is coined

26 Apr 1927

Anne McLaren was born in London, UK

1942 - 1945

Animal experiments launched to investigate the biological effects of acute and chronic exposure to different forms and intensities of ionising radiation

1942 - 1945

One part of the blood system, the spleen, offers some form of protection against radiation damage

1945

Research continues into the damaging effects of ionising radiation upon the blood system - the tissue most sensitive to radiation effects

1945

Atomic Energy Research Establishment (AERE) founded

1947

Medical Research Council Radiobiological Unit (MRC RU) established

1949

First experiments transplanting spleen from non-radiated mice into radiated mice

23 Mar 1950

Hubert Schoemaker was born in Deventer, The Netherlands

1951 - 1956

Debate about whether the 'recovery factor' present in the spleen and marrow is a hormone or a cell

1951

Transfer of marrow into lethally irradiated mice shows that marrow, like spleen, is regenerative

1956

Experiments with mice confirm radiation recovery factor is a distinctive cell

1956

Mice with leukaemia treated successfully with lethal radiation followed by bone marrow transplant

12 Sep 1957

First report of successful bone marrow transplants performed in human patients

1959

Infused allogeneic bone marrow in accidentally irradiated workers shown to give rise to mature blood cells

1959

Bone marrow transplants in two sets of identical twin girls fails to eradicate leukaemia

1959

Experiments in mice prove the existence of resident blood stem cells in marrow

1960

Bone marrow transplants being undermined by immunological reactions (especially graft-versus-host-disease (GvHD))

1961

Existence and properties of transplantable stem cells in mouse bone marrow established and the first methodology for counting them is devised

1962 - 1965

Bone marrow transplants in humans abandoned by Thomas group due to graft-versus-host-disease

1962

Nuclei from adult frog cells reprogrammed to full embryonic potential after transfer into frog eggs

1965

First successful allogeneic marrow transplant reported in patient with leukaemia

1965

Distinctive and powerfully regenerative cell resident in bone marrow, known from now on as stem cells

1965

Paterson Institute for Cancer Research established as a major centre for blood stem cell research

1965

Development of a technique for the in vitro cultivation of bone marrow cells

1968

First successful bone marrow transplant from a sibling

1969

Concept of the tumour stem cell is born

1970

Blood stem cell proves highly elusive as it is difficult to isolate and visualise

1971

Cetus Corporation, the first biotechnology was founded

1973

First successful bone marrow transplant from unrelated donor

1975

A liquid media is developed for growing bone marrow cells, including the blood stem cell

1977

Bone marrow transplants is clinically proven

1978

Transplantable stem cells discovered in human cord blood

1980 - 1990

Existence of the blood stem cell contested

9 Jul 1981

Mouse embryonic stem cells first isolated and cultured in the laboratory

Dec 1981

Another method published for cultivating mouse embryonic stem cells

1982

Leukaemia emerges as a key means for understanding of the role of the stem cell in cancer

1982

Amcell, a private biotechnology company, is formed to commercialise blood stem cells

1982

Marrow stem cells shown to be distinct from progenitor cells

1982

AIS, the first biotechnology company to commercialise blood stem cell-based innovation is established

1984

A molecular marker, CD34, is identified as specific for a subset of marrow cells containing the blood stem cell

1984 - 1996

Ongoing litigation between CellPro and Baxter Healthcare Corporation over the use of the CD34 marker for cell separation technology

1984

CD34 marker used as the basis for cell separation technology

1984

Blood stem cells extensively purified for first time

1986

National Marrow Donor Programme established in US

1987

First clinical trials of foetal neural cell grafting in patients with Parkinson’s disease

1987

CellPro, the second biotechnology company is formed to commercialise blood stem cells

1988

First reported clinical use of umbilical cord blood

1988

SyStemix, the third biotechnology company is established to commercialise blood stem cells

1 Jul 1988

The first hematopoietic stem cells were isolated in mice

1989

Aastrom, a private biotechnology company is formed to commercialise blood stem cells

1990

Some companies attempt, but do not succeed, to develop blood stem cell-based business

1990

Discovery of the nesting gene, the most commonly used marker for neural stem cells

1990

Mouse marrow regenerating stem cells are completely separated from in vivo colony-forming cells for first time

1992

First public bank set up for umbilical cord blood bank in New York

1992

Neural stem cells identified in the adult human brain

1992

Progenitor, a private biotechnology company is formed to commercialise blood stem cells

1992

Stem cells used as vectors to deliver the genes needed to correct the genetic disorder SCID

1993

Embryonic stem cells are proven to be pluripotent; having the ability to differentiate into different cell types

1994

First separation of cancer stem cells from the majority of cells in a cancer

1994

Patients with damaged corneas successfully treated with corneal stem cells

1994

Cancer stem cell theory advanced

1994

Experiments in adult rats indicate olifactory ensheathing cells could regenerate injured dorsal root axons in spinal cord

1995

First derivation of primate embryonic stem cell lines

1996

First reports that blood stem cell might be able to give rise to cells other than those of the blood system

1996 - 2002

Experiments with rats conducted by different research teams around the world confirm olifactory ensheathing cells help repair spinal cord

1998

Human brain demonstrated to contain cells with stem-like properties

Oct 1998

First human embryonic stem cell line derived

1999

Adult neural stem cells identified as capable of forming new neural stem cells

1999

Neuronyx founded

2000

Adult stem cells recognised as having potential to generate variety of cells for other organs

2000

Retinal stem cells identified in mice

5 Dec 2000

Wisdom teeth demonstrated to be source of stem cells

2001

The Stem Cell Network is formed

2001

Dermal stem cells identified in adult skin tissue

2001

US places restricitions on embryonic stem cell research

Oct 2001

Human embryo cloned to make stem cells

2002

International Society for Stem Cell Research (ISCF) established

2002

First complete purification of multipotent marrow stem cells from mice

4 Mar 2002

Canadian Institutes of Health Research unveiled guidelines for stem cell research

2003

Cancer stem cells isolated in human brain tumours

14 Feb 2003

Dolly the sheep, the first cloned mammal, died

13 May 2003

Dental pulp from baby teeth demonstrated to be source for stem cells

2004

First derivation of dopaminergic cells from human embryonic stem cells

2004

International Consortium of Stem Cell Networks (ICSCN) initiated

2005

Lasker Prize awarded to James Till and Ernest McCulloch

2005

First evidence for human bone cancer stem cells

2005

UK Pattison Report emphasizes stem cells as likely potential therapies for the future

15 Jun 2005

Canadian researchers created the country's first embryonic stem cell lines

25 Aug 2005

Harvard scientists reported reprogramming adult skin cells into embryonic stem cells

2006

Normal mammary stem cells demonstrated in adult mice

1 Jan 2006

Hubert Schoemaker died in Philadelphia, USA

12 Jan 2006

First successful cloning of human embryo to make stem cells

Jun 2006

Four genes identified as important for reprogramming cells

16 Nov 2006

Stem cell injections reported to ease symptoms in muscular dystrophy in dogs

2007

Nobel Prize for Physiology for Medicine awarded for discoveries enabling germline gene modification in mice using embryonic stem cells

2007

First physical identification and localization of mammalian intestinal stem cells

2007

First evidence for human colon cancer stem cells

Jan 2007

Scientists isolated new stem cell source in amniotic fluid

Feb 2007

Stem cell transplant used to treat leukaemia in a patient found to cure his HIV

Apr 2007

Canadian researchers converted normal human blood cells into leukaemia stem cells to investigate leukaemia

Jun 2007

Skin cells reprogrammed to become like embryonic stem cells

7 Jul 2007

Anne McLaren died

5 Sep 2007

British regulators approved human-animal embryo research

30 Nov 2007

Human cells reprogrammed to make pluripotent stem cells

2008

Gairdner Prize is awarded to Sam Weiss for the discovery of neural stem cells

5 Sep 2008

Scientists created stem cells for 10 disorders

2009

Lasker Prize awarded to John Gurdon and Shinya Yamanaka for discoveries in nuclear reprogramming. Yamanaka is also awarded the Gairdner Prize

2009

Induced pluripotent stem cells created with minimal residual genomic alteration

Jan 2009

First animal tests suggest stem cells may reverse paralysis

11 Feb 2009

Stem-cell transplant reported to be promising treatment for curing HIV

Mar 2009

Embryonic like stem cells generated from adult human tissue

9 Mar 2009

U.S. President Barack Obama reversed restrictions on stem cell research imposed by former President George W. Bush

10 Jun 2009

Stem cell transplants reported to improve survival for leukaemia patients

2010

Adult cells reprogrammed into neurons, cardiac muscle and blood cells

2010

First clinical trial of human embryonic-derived stem cells for treatment of spinal cord injury

5 Nov 2010

Modified mRNA reported to transform skin cells into pluripotent stem cells

2011

Isolation of multipotent human blood stem cells capable of forming all cells in the blood system

10 Mar 2011

Patient suffering from acute myeloid leukaemia is cured of HIV-1 after receiving bone marrow stem cells transplanted from donor with mutated CCR5 gene. This awakens interest in developing HIV treatment that renders a patient's cells resistant to HIV-1

Apr 2011

US funding of embryonic stem cell research permitted

14 Jul 2011

First safety trial launched in humans to test embryonic stem cell therapy to treat blinding diseases

2012

John Gurdon and Shinya Yamanaka win the Nobel Prize in Physiology or Medicine for the discovery that mature cells can be reprogrammed to become pluripotent stem cells

2014

Japanese scientists completed successful skin-to-eye stem cell transplant in a 70 year old patient with age-related macular degeneration, a blinding disease.

Mar 2014

Breakthrough for manufacturing stem cells

5 Jun 2014

First embryonic stem cells cloned from a man's skin

Oct 2014

Stem cells taken from nose demonstrated to repair spinal cord injury

29 Sep 2015

First UK patient recieved experimental stem cell treatment for age-related macular degeneration

20 Oct 2015

UK NHS sets up stem cell factory in Liverpool to supply experimental treatment for people with diabetes

8 Mar 2016

UK scientists link repeated miscarriages to a reduction of stem cells in lining of the womb

9 Mar 2016

A dozen infants born with cataracts reported to regain sight after receiving new stem cell therapy

17 Mar 2016

Scientists announce the first generation of an embryonic stem cell that carries a single copy of the human genome rather than the usual two

23 Mar 2016

Surgeon involved in world's first trachea transplant made from patient's own stem cells sacked for scientific misconduct

2 Jun 2016

Stem cells reported to provide substantial recovery in patients disabled by stroke

24 Jul 2016

Small-scale case study showed power of stem cells to repair damaged scar tissue caused by heart attacks

20 Feb 2017

Data published from 25 centres in 13 countries for 281 patients indicated autologous hematopoietic stem cell transplantation can halt the progression of MS disability

2 Mar 2017

Gene therapy reported to successfully reverse sickle cell disease in first patient

3 Mar 2017

Cambridge scientists report the development of an aritificial mouse embryo using stem cells

16 Mar 2017

Study published showing a personalised treatment using a patient's own stem cells effective for treating macular degeneration, a common blinding disease

16 Mar 2017

Follow-up of three women given stem cell treatment in 2015 to treat macular degeneration raises concerns

Apr 2017

Researchers at University of Washington-Madison demonstrated the possibility of growing skin, bone marrow and blood vessels using plant scaffolds with stem cells

4 Oct 2017

Gene therapy shown in clinical trials to halt progression of adrenoleukodystrophy, a fatal brain disease inherited by boys

14 Nov 2017

Stem cells in the body found to have significantly different gene-expression profile than stem cells isolated and cultivated in the laboratory

19 Mar 2018

Stem cell treatment reported to be promising treatment for age-related macular degeneration

7 Dec 2018

Mouse and human skin cells reprogrammed into immune cells to fight cancer

5 Mar 2019

Second patient reported free of HIV after receiving stem-cell therapy

19 Apr 2019

Gene therapy shown to be promising in treating infants born with X-linked severe combined immunodeficiency (SCID-X1)

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