Stem Cell Research Timeline

On October 15, 1958, a criticality accident at the Vinča nuclear institute near Belgrade exposed five young physicists to near-lethal radiation. They were flown to Paris, where Georges Mathé of the Institut Curie gave all five marrow from unrelated volunteer donors matched only by blood type. Four of the five recovered. The donor cells did not last long term, but the grafts helped carry the patients through the period when their own marrow was failing.

In 1961, the researchers conducted experiments involving the transplantation of bone marrow cells into mice that had previously received radiation. Several days later, they observed bumps on the spleens of the mice that had received transplants and discovered that each lump contained a colony of cells capable of giving rise to the multiple cell types that make up human blood.These landmark findings provided the first description of blood-forming stem cells.

The donor and patient were siblings who were not identical twins, matched by tissue typing. The transplant restored the boy’s immune system and he survived into adulthood. The case helped establish tissue matching as the standard for bone marrow transplants.

On July 12, 1974, President Richard Nixon signed the National Research Act (Pub. L. 93-348) into law, which legally created the Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. On August 23, 1974, the Secretary of Health, Education, and Welfare formally approved the operational charter, allowing the group to begin its official work.

The 1975 regulations were jointly published in the Federal Register on August 8, 1975 (40 FR 33526) with the report and recommendations of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, Research on the Fetus.

The EAB had recommended federally funded investigations into the safety of in vitro fertilization using human embryos developed in vitro for no more than 14 days, but a de facto moratorium halts federal funding of human embryo research due to the EAB”s disbanding.

The cells came from mouse blastocysts, the early embryo stage a few days after fertilization. They kept normal chromosomes in culture and could form many cell types. Evans later shared the 2007 Nobel Prize for work built on these cells.

Martin grew cells from the inner cell mass of mouse blastocysts in a medium conditioned by tumor-derived stem cells. Her work and that of Evans and Kaufman appeared within months of each other. Together they established mouse embryonic stem cells as a research tool.

Despite the panel’s support, HHS Secretary Louis Sullivan extended the moratorium indefinitely on November 2, 1989. 1988 Moratorium: The Department of Health and Human Services (HHS) enacted a ban on federal funding for transplantation research using fetal tissue from induced abortions.

The donor was Matthew’s newborn sister, who had been tested before birth to confirm she did not have the disease and was a tissue match. Her cord blood was collected at birth and frozen by Hal Broxmeyer’s team in the United States, then flown to Paris. The transplant cured Matthew’s Fanconi anemia and opened the way for cord blood banking.

Thomas, of the Fred Hutchinson Cancer Research Center in Seattle, developed bone marrow transplantation to treat leukemia and other blood diseases. Murray performed the first successful kidney transplant. The prize was announced on October 8, 1990.

In 1992, congressional efforts to lift the federal ban on using fetal tissue from induced abortions in transplantation research were blocked when President George H.W. Bush vetoed the legislation. The moratorium stayed in place until President Clinton lifted it on January 22, 1993.

By eliminating the ban, Clinton allowed researchers to utilize federal funds for transplantation studies that had the potential to treat serious illnesses like Parkinson’s disease, Alzheimer’s disease, and diabetes. This historic reversal was formalized shortly after through the National Institutes of Health Revitalization Act of 1993, which officially codified the policy into law.

In December 1994, despite receiving recommendations from a National Institutes of Health (NIH) panel to fund human embryo research, President Bill Clinton directed NIH not to fund the creation of human embryos for research. He specifically blocked the NIH from supporting research involving the creation of human embryos for experimental purposes. Following this executive halt, Congress enacted the Dickey-Wicker Amendment in 1995, which formally codified the ban on using federal funds for the destruction, creation, or discarding of human embryos. This marked the beginning of a complex, decades-long debate on the ethics of federal.

The amendment prohibits the use of federal funds for “the creation of human embryo or embryos for research purposes; or research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death greater than that allowed for research on fetuses in utero.”

Scientists led by Ian Wilmut used somatic cell nuclear transfer, moving the nucleus of an adult udder cell into an egg cell with its nucleus removed. Her birth was kept private until it was announced on February 22, 1997, and the study was published in Nature on February 27, 1997. Dolly showed that adult cells can be reprogrammed to produce a whole animal.

This breakthrough was published in the journal <i>Science</i> in November 1998. This discovery also initiates the ethical debate on human embryonic stem cell research because his team derives the stem cells through a process that destroys human embryos.In 2007, Thomson’s lab developed Induced pluripotent stem cells (iPSCs) to bypass embryo use.

The opinion determined that stem cells were not “human embryos” under statutory definitions, thereby allowing federal funding for research using existing hESC lines. NIH Director Harold Varmus receives a legal opinion from DHHS general counsel Harriet Rabb. Rabb finds that the Dickey-Wicker amendment does not apply to federal funding for research on embryonic stem cells because the cells do not meet the statutory definition of an embryo. The cells, however, would have to be derived with private funding.

A few years later, in 2003, a team including Songtao Shi at the NIH, with Masako Miura as a lead author, reported a related population in baby teeth, which they called stem cells from human exfoliated deciduous teeth (SHED).

The policy does not affect research in the private sector or research conducted with state funding. The president claimed that more than 60 stem cell lines would be available for funding. The policy was intended as a compromise.

The President”s Council on Bioethics, chaired by Leon Kass, publishes Monitoring Stem Cell Research, a report that contains “no proposed guidelines and regulations, nor indeed any specific recommendations for public policy.” But according to Kass, the overarching goal of the report is “to convey the moral and social importance of the issue at hand and to demonstrate how people of different backgrounds, ethical beliefs, and policy preferences can reason together about it.”

The Act makes conducting stem cell research a state constitutional right. It authorizes the sale of general obligation bonds to allocate three billion dollars over a period of ten years to stem cell research and research facilities. Although the funds could be used to finance all kinds of stem cell research, it gives priority to human embryonic stem cell research.Proposition 71 created the California Institute for Regenerative Medicine (CIRM), which is in charge of making “grants and loans for stem cell research, for research facilities, and for other vital research opportunities to realize therapies” as well as establishing “the appropriate regulatory standards of oversight bodies for research and facilities development”.The Act also establishes a governing body called the Independent Citizen’s Oversight Committee (ICOC) to oversee CIRM.

These guidelines introduced the requirement for Embryonic Stem Cell Research Oversight (ESCRO) committees and established strict protocols for donor consent, ensuring that stem cell research was conducted safely and ethically amid a lack of comprehensive federal regulations at the time.

The report proposed four primary approaches to address ethical concerns: non-harmful biopsy, harvesting from dead embryos, Altered Nuclear Transfer (ANT), and cellular reprogramming.

The law set up a national cord blood inventory and the C.W. Bill Young Cell Transplantation Program for bone marrow and cord blood transplants. It funded public cord blood banks to collect and store units for patients who need a donor.

Hwang’s team had claimed to create patient-matched embryonic stem cell lines through cloning. A university investigation concluded the key results were faked. Science declared the reported results invalid and withdrew both papers.

The Stem Cell Research Enhancement Act (H.R. 810) aimed to expand federal funding for human embryonic stem cell research by allowing the use of stem cells derived from embryos donated from in vitro fertilization clinics. However, it was vetoed by President George W. Bush on July 19, 2006, who argued it crossed a moral boundary by supporting the destruction of human embryos.

The bill would have allowed federal funding for research on embryonic stem cell lines made from embryos donated by fertility clinics. The House failed to override the veto. Federal funding remained limited to lines created before August 9, 2001.

The four genes were Oct3/4, Sox2, c-Myc and Klf4. The resulting cells, called induced pluripotent stem cells, were made without using embryos. The same approach was applied to human cells in 2007.

The guidelines outline core principles and best practices for the field.

The order expands the NIH Embryonic Stem Cell registry to include all types of ethically produced human pluripotent stem cells. The order renames the registry to the Pluripotent Stem Cell Registry.

Their method lets scientists switch off or alter a chosen gene in mouse embryonic stem cells and then breed mice carrying the change. These “knockout” mice became a standard tool for studying human disease. Evans was one of the first scientists to grow mouse embryonic stem cells, in 1981.

The pluripotent cells were created from skin cells that had four genes inserted into them with viruses. This procedure resulted in the skin cells acquiring properties similar to embryonic stem cells. Researchers were able to coax these so-called iPS cells into becoming beating heart cells and nerve cells.

The amendment, now Article I, Section 27 of the Michigan Constitution, lets researchers use embryos created for fertility treatment that would otherwise be discarded, when donors give written consent. It bars taking stem cells from embryos more than 14 days after cell division begins, bans buying or selling embryos, keeps Michigan’s ban on human cloning, and blocks state and local laws that restrict permitted stem cell research.

Geron Corp, the company behind the research, was authorized to initiate a clinical trial in a handful of patients paralyzed due to spinal cord injury. The company later decided to discontinue its stem cell trial for spinal cord injury patients in an effort to focus on its oncology program. The stem cell assets were later acquired by BioTime, which indicated plans to restart the trial. Participants from the original trial continue to be monitored for 15 years.

This Executive Order by President Obama revokes the Executive Order signed by President Bush on June 20, 2007 and the Bush Presidential statement of August 9, 2001 that limited federal funding of research involving human embryonic stem cells.

The judge found the funding likely violated the Dickey-Wicker Amendment. An appeals court paused the injunction on September 9, 2010, and federal funding resumed. Courts later ruled in favor of the NIH guidelines.

The phase 1 trial of GRNOPC1 was designed to test safety, not to cure paralysis. Geron ended the trial in 2011 to focus on cancer drugs. Patients in the trial continued to be followed for safety.

The cause of death is unknown. McCulloch was born in Toronto and worked as a lead researcher at the Ontario Cancer Institute and the Institute of Medical Science at the University of Toronto.

Hemacord is approved for unrelated-donor transplants in patients with disorders of the blood-forming system. The approval followed FDA rules requiring public cord blood banks to license their products or run them under investigational applications.

The cells come from the bone marrow of healthy adult donors and do not require tissue matching. Health Canada described it as the first stem cell therapy indicated for clinical use in patients. The approval was conditional on further studies confirming benefit.

Gurdon showed in 1962 that the nucleus of a mature frog cell could produce a whole tadpole. Yamanaka showed in 2006 that four genes could turn mouse skin cells into stem cells. Their work showed that a cell’s specialized state can be reversed.

The papers, led by Haruko Obokata of RIKEN, were published in January 2014. Other labs could not reproduce the results, and a RIKEN investigation found research misconduct. The authors agreed to withdraw both papers.

Researchers made a sheet of retinal pigment epithelium cells from the patient’s own skin cells and placed it under her retina. The study was designed to test safety. Follow-up found no rejection or tumors, and her vision stabilized rather than improved.

Holoclar is grown from limbal stem cells taken from the patient’s healthy eye tissue. It is used for moderate to severe limbal stem cell deficiency. The conditional approval became a standard approval on February 22, 2024.

The cells come from the bone marrow of healthy adult donors, using technology licensed from Osiris Therapeutics. JCR described it as the first allogeneic regenerative medicine product approved in Japan.

Omisirge is made from umbilical cord blood that is processed and expanded in the lab. It is for patients 12 and older who are planned for cord blood transplants after high-dose treatment.

Casgevy is made by editing a patient’s own blood stem cells and returning them after chemotherapy. It is approved for patients aged 12 and older. The therapy was developed by Vertex Pharmaceuticals and CRISPR Therapeutics.

Both treatments modify the patient’s own blood stem cells, which are returned after chemotherapy. Casgevy uses CRISPR gene editing, and Lyfgenia uses a viral vector to add a modified gene.

Ryoncil is made from bone marrow cells of healthy adult donors. It is the first mesenchymal stromal cell therapy approved by the FDA. The same product was approved in Canada as Prochymal in 2012.

The registry was created pursuant to President Barack Obama’s Executive Order 13505, Removing Barriers to Responsible Scientific Research Involving Human Stem Cells.