History & timeline.
A measured, clinician-facing account: what regenerative therapy sets out to do, what the current literature reports, and the sourced history of how the field arrived where it stands today—presented without claims about any product.
The Field / Origins
How the field got here, and what is actually settled
A sourced history of the field's aims and milestones — scientific firsts, regulatory decisions, court rulings, and hard lessons, from a 1909 hypothesis to the present. It records what happened; it makes no claim about any treatment.
What this page is, and is not
This page describes the history of a scientific field and the regulatory determinations made about it by named government agencies. Every entry reports something that happened: a published finding, a clinical first, a decision by a regulator, a court ruling, or a documented harm. Determinations are attributed to the agency or court that made them and sourced to primary documents.
It does not describe, evaluate, endorse, or support any use of any product available through the laboratories we work with. Those are human cells, tissues, and cellular and tissue-based products regulated under Section 361 of the Public Health Service Act, and are prepared in FDA-registered laboratories — establishments registered with, and subject to inspection by, the FDA. Registration of a facility, however, is not approval of a product: these products are not FDA-approved. An approval granted to another product, by another regulator, in another country, for another condition confers nothing on them, and nothing on this page should be read as suggesting otherwise. No cord-derived or other perinatal-tissue product holds an FDA biologics license for any musculoskeletal, orthopedic, or pain indication.
Entries are included because they changed the field's direction — including the ones that reflect poorly on it, and including approvals for indications that resemble uses now offered in practice. Omitting those would make this a more comfortable document and a less honest one.
Regenerative therapy is organized around a single aim: to repair, replace, or restore damaged tissue. Whether that aim has been achieved is a separate question, and the answer differs enormously depending on which tissue, which condition, and which product is being discussed.
That is an aim, not a claim — and the distinction is the most important thing to carry into what follows. The field spans an enormous range of maturity. Some of what sits under the regenerative banner has fifty years of clinical evidence, licensed products, and standard-of-care status. Some is still in early investigation. Some has been tried and did not work.
The history is the clearest way to tell those apart. What follows is not a complete record — the field is far too large for that. It is the sequence of moments where something became possible that had not been possible before, where the evidence became strong enough to change practice, and, in a few cases, where the field had to correct course.
Two lineages
Cells and tissue can come from the patient (autologous) or from a donor (allogeneic). The two paths solve different problems and face different obstacles. They are tracked separately below; foundational science sits on the center line.
A global history, a US framework
The science has never been confined to one country — key work came from Germany, Russia, Canada, France, Japan, and Korea. Every entry is marked with where it happened. Regulatory entries center on the US framework, which governs these products here. Federal law regulates the products; the practice of medicine is regulated by the states.
What "approved" means here
"Approved" is a specific legal status granted by a named regulator, and is identified as such wherever it appears. Every approved product below is a licensed biologic — reviewed under Section 351 of the Public Health Service Act, or its equivalent abroad. None is a Section 361 tissue product. Products regulated under Section 361 do not undergo premarket review, which means approval is not a status available to them: no 361 product can appear on this timeline as approved, because none is ever approved.
Inclusion is not endorsement
An entry appears because it changed the field's trajectory — including the failures. Nothing is listed here because it is recommended, available, or advisable.
The founding idea
Entries in this period concern the proposal that some cells both renew themselves and produce specialized descendants, and the first experiments to test it. The work spans Berlin, St Petersburg, and Toronto.
The premise nearly every later search began from
Alexander Maximow, of the St Petersburg Military Medical Academy, tells the Berlin Hematological Society on June 1 that every type of blood cell descends from a single common precursor, publishing the argument in Folia Haematologica the same year. The hematopoietic stem cell hypothesis becomes the organizing idea of the field.
Bone marrow as a therapy
E. Donnall Thomas transfuses bone marrow between identical twins, publishing the first human series the following year. Cellular material — not an organ — is used to reconstitute a failing system.
A theory becomes countable
James Till and Ernest McCulloch, in Toronto, show that single marrow cells can give rise to multiple blood lineages, using a spleen colony assay that makes the cells countable for the first time. Follow-up work two years later establishes that those cells also self-renew.
From laboratory to bedside
Entries in this period cover the first sustained clinical use of cell therapy, and the separation of patient-derived and donor-derived approaches into distinct lines of work.
The first successful allogeneic procedure
Robert Good's team at the University of Minnesota infuses marrow from a matched sibling into an infant with severe combined immunodeficiency. The patient survives.
A second population in marrow
Alexander Friedenstein identifies a non-blood-forming, colony-forming cell in bone marrow capable of generating bone and cartilage. This is the ancestor of what would later be called mesenchymal.
Skin grown from the patient
Cultured epidermal autografts are used to cover severe burns with sheets grown from the patient's own cells — one of the first therapies where cells are manufactured rather than merely transferred.
Birth tissue enters the clinic
Eliane Gluckman performs the first umbilical cord blood infusion in Paris — a child with Fanconi anemia receives cells from a sibling’s cord blood.
"Mesenchymal stem cells" named
Arnold Caplan gives Friedenstein's marrow stromal population a name and a research program. The term will later be applied — often loosely — across a very wide range of products.
Tissue engineering gets a definition
Robert Langer and Joseph Vacanti publish a framework in Science for building living tissue on engineered scaffolds, formalizing a field.
Frameworks, reprogramming, and reported harms
Entries in this period cover the regulatory frameworks built in the US and the EU to separate minimally processed tissue from manufactured biologics, the first reprogramming experiments, and cases in which reported harms followed early clinical use.
2005
The HCT/P framework takes shape
The FDA builds 21 CFR Part 1271 in stages: establishment registration and product listing in 2001, followed by donor eligibility and current good tissue practice requirements effective in 2005.
2007
Induced pluripotency
Shinya Yamanaka, at Kyoto University, shows that four genetic factors can return an ordinary adult cell to a pluripotent state — capable of becoming any tissue type. First demonstrated in mouse cells, then in human ones.
2009
Europe defines advanced therapies
Regulation (EC) No 1394/2007 creates a unified category — Advanced Therapy Medicinal Products — covering gene therapy, cell therapy, and engineered tissue. A dedicated Committee for Advanced Therapies is seated at the EMA in 2009.
2016
The engineered airway
A tissue-engineered airway procedure is performed in Barcelona and celebrated worldwide. Subsequent synthetic-scaffold operations at another institution lead to patient deaths, retracted papers, and one of medicine’s most serious research misconduct investigations.
Regulatory approvals, and where they happened
Entries in this period cover cell therapies clearing regulatory review. Several were approved outside the United States, under pathways with different evidentiary requirements.
None of the licensed products in this era — or anywhere on this timeline — is offered by the laboratories we work with, and none is comparable to the Section 361 material supplied for tissue practice, which is not FDA-approved. With that understood, read the indications closely. Each approval below covers a single named condition, reviewed on trial data specific to that condition. No cord-derived or other perinatal-tissue product holds an FDA biologics license for any musculoskeletal, orthopedic, or pain indication. Note also that cord blood and cord tissue are different source materials with different clinical histories. Approval of one product for one use says nothing about any other product or any other use.
The first licensed cellular immunotherapy
Provenge (sipuleucel-T) is approved for asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer: a patient's own immune cells are collected, processed to recognize a tumor antigen, and returned.
Cord blood becomes a licensed product
Hemacord is the first cord blood product to receive a US biologics license, twenty-three years after the first cord blood transplant. Further cord blood licenses follow.
The first approved MSC product anywhere
Korea's Ministry of Food and Drug Safety approves Hearticellgram-AMI, an autologous bone marrow MSC product delivered by coronary artery injection after heart attack.
The first approved cord-derived product
Cartistem, an allogeneic umbilical cord blood-derived MSC preparation for knee cartilage defects, is approved in January — the first manufactured MSC product sourced from perinatal tissue to be approved anywhere in the world.
The first approved off-the-shelf stem cell drug
Health Canada authorizes Prochymal (remestemcel-L) in May for pediatric graft-versus-host disease, under a conditional pathway requiring confirmatory trials. New Zealand follows weeks later.
The first child to receive CAR-T
A six-year-old with refractory leukemia receives her own T cells, genetically engineered to target CD19. She enters remission — and remains in it, becoming the case that convinces the field.
Japan moves first on iPS cells — and on the rules
In September, Masayo Takahashi's team at RIKEN transplants a retinal sheet grown from a patient's own reprogrammed cells — the world's first clinical use of iPS cells. Weeks later, new legislation creates a conditional, time-limited approval pathway for regenerative products. A donor-derived version of the procedure follows in 2017.
Engineering, editing, and enforcement
Entries in this period cover engineered and gene-edited cell products, and US court decisions and enforcement actions addressing what requires approval.
None of the licensed products below — or anywhere on this timeline — is offered by the laboratories we work with, and none is comparable to the Section 361 material supplied for tissue practice, which is not FDA-approved. The approvals here are licensed biologics reviewed under Section 351 — individually manufactured cell products, engineered T cells, donor islet cells, and one donor-derived MSC therapy, each for a single named condition. None is a Section 361 tissue product.
Three patients lose vision at a Florida clinic
The New England Journal of Medicine reports in March that three women in their seventies and eighties, seen for macular degeneration at a Florida clinic in 2015, received injections of autologous adipose-derived cells into both eyes. All three lost most or all remaining vision.
Source: Kuriyan AE et al. Vision loss after intravitreal injection of autologous "stem cells" for AMD. N Engl J Med 2017;376:1047–1053.
CAR-T reaches the market
Kymriah is approved in August for pediatric leukemia, followed by Yescarta in October for lymphoma. Both are manufactured individually from each patient's own T cells.
Enforcement discretion ends
On May 31, 2021, the FDA's transitional policy for HCT/Ps that did not clearly meet the Section 361 criteria comes to an end.
2025
Two circuits reach the same conclusion
In June 2021 the Eleventh Circuit held that a Florida clinic's adipose stromal vascular fraction procedure met neither the same-surgical-procedure exception nor the Section 361 criteria, and was therefore a drug requiring approval. In September 2024 the Ninth Circuit reached the same conclusion in a California case, reversing a district court that had ruled the other way. The Supreme Court declined to review that decision on October 14, 2025.
Sources: United States v. US Stem Cell Clinic, LLC, 998 F.3d 1302 (11th Cir. 2021) · United States v. California Stem Cell Treatment Center, No. 22-56014 (9th Cir. 2024) · Sup. Ct. Docket No. 24-1189
The first gene-edited therapy, approved
In November the UK's MHRA authorizes Casgevy for sickle cell disease and beta thalassemia — the world's first approved CRISPR-based medicine. The FDA follows three weeks later for sickle cell disease alone, approving Lyfgenia, a lentiviral gene therapy, the same day; the beta thalassemia indication is added in 2024.
Donor islet cells for type 1 diabetes
Lantidra becomes the first licensed allogeneic pancreatic islet cell therapy, for a narrow group of adults with type 1 diabetes who experience repeated severe hypoglycemia despite intensive management.
The first MSC therapy approved in the US
On December 18, Ryoncil (remestemcel-L) is approved for steroid-refractory acute graft-versus-host disease in children — donor-derived bone marrow mesenchymal stromal cells, supplied off the shelf.
China's first stem cell therapy — from cord tissue
On January 2, the National Medical Products Administration grants conditional approval to Ruibosheng (amimestrocel), a human umbilical cord-derived mesenchymal stromal cell injection, for steroid-refractory acute graft-versus-host disease with predominant gastrointestinal involvement in patients aged 14 and over.
Source: National Medical Products Administration announcement.
A narrow core, and a much larger field around it
A defined set of cell and gene therapies now hold full marketing approval. Alongside them sit thousands of active clinical trials worldwide, and a far larger volume of tissue-based practice operating outside the approval process entirely — some of it regulated under Section 361, some of it the subject of the enforcement actions and litigation described above.
Illustrative process overview. Processes and requirements vary by product and supplier; applicable product-specific documentation controls.
Reading the field from here
Three patterns run through this timeline. A concept precedes its evidence by decades. Evidence precedes clinical use by years. And regulatory clarity almost always arrives last — differently in each country, which is why the same product can be approved in one jurisdiction while still under review in another.
Every approved therapy above reached patients by generating data, submitting it to review, and accepting the answer. The cautionary entries are here because they show what happens when that sequence is skipped — in a leading academic center, in private practice, and in court. That sequence — data, review, and acceptance of the answer — is what separates the reviewed parts of the field from the rest of it.
One practical note for anyone reading this to inform a decision. An approval is specific to a product, a manufacturer, an indication, and a country. It does not transfer to a similar product, a different use, or a different jurisdiction. Most of what is available in practice today has not been through that process, which is a statement about regulatory status rather than about any individual product's merit.
Read this before you use anything on this page
Nothing on this page is a recommendation to treat any patient. It contains no protocol, no indication, no dose, no route, no patient-selection criterion, and no suggestion that any condition described here can be treated with anything the laboratories we work with make available. No entry should be read as guidance, encouragement, or implied support for any clinical use. If any passage here reads to you as pointing toward a use, that reading is not intended and is not correct. Nothing on this page asserts that any therapy described here is safe or effective for any condition. Research findings are reported as published; they are not claims of clinical efficacy.
No product prepared by the laboratories we collaborate with is FDA-approved. They are human cells, tissues, and cellular and tissue-based products regulated under Section 361 of the Public Health Service Act, and are prepared in FDA-registered laboratories. Registration of a facility is not approval of a product: products in that category do not undergo premarket review, which is not the same as approval and must not be described or understood as approval. No product from any laboratory we collaborate with appears anywhere on this timeline.
Approvals do not transfer. An approval is granted to one product, made by one manufacturer, for one named indication, by one country's regulator, on the strength of trial data specific to that product and that indication. It confers nothing on a similar product, a related tissue source, a different use, or a different jurisdiction. Approvals granted outside the United States carry no US regulatory status whatsoever. Most of what is available in practice today has never been through any approval process anywhere.
Clinical, regulatory, and legal judgment remain entirely yours. Nothing here is medical, legal, or regulatory advice, and none of it substitutes for your own review of the primary literature, the current regulations in your jurisdiction, or the counsel of your own attorney. Meridian Biologics does not evaluate protocols, does not advise on whether a use is permissible, and will decline to do so if asked.
Milestone dates, regulatory determinations, and court rulings are drawn from primary sources including the FDA's list of Approved Cellular and Gene Therapy Products, announcements from the EMA, MHRA, Health Canada, Japan's PMDA, Korea's MFDS and China's NMPA, published federal appellate opinions, and the peer-reviewed literature. Where an entry reports a regulator's determination, that determination belongs to the named agency and not to this company. Last reviewed and updated: July 2026.