Current Landscape of FDA Stem Cell Approvals and Trials 2023-2025

2025 marks a turning point in the clinical development of stem cell therapeutics, as significant regulatory and clinical milestones have been or will be reached in various stem cell programs, including Mesenchymal Stem Cell (MSC)and induced Pluripotent Stem Cell (iPSC)therapies. This progress has been enabled by structured Phase I-III trials and sometimes supported by expedited FDA designations such as regenerative medicine advanced therapy (RMAT) and Fast Track (FDA, 2019). This blog will unpack the 2023-2025 stem cell landscape - from newly FDA-approved therapies like the first U.S. MSC treatment (Ryoncil) to pivotal stem cell clinical trials backed by designations such as RMAT and Fast Track.

Global Pluripotent Stem Cell Trial Landscape: iPSC and ESC

Pluripotent stem cell (PSC) clinical trials, including human iPSCs and embryonic stem cells (ESCs), center on harnessing the extraordinary ability of these cells to become virtually any cell type in the body. Clinical trials using PSCs span a wide therapeutic range. As of December 2024, a major review identified 115 global clinical trialsinvolving 83 distinct PSC-derived productstargeting indications in ophthalmology, neurology, and oncology (Figure 1). Over 1,200 patientshave been dosed with more than 10¹¹ cells, with no significant safety concerns reported (Kirkeby et al., 2025).

The overall safety profile of iPSC-based clinical trials to date is encouraging, with no class-wide safety concerns observed.However, the specific disease being treated and how the therapy is given, e.g. by injection or infusion remain considerations, highlighting the need for continued long-term surveillance of patients. Such PSC programs require Investigational New Drug (IND) approval and typically will progress through structured Phase I-III trials, sometimes supported by FDA designations that facilitate regulatory engagement and trial acceleration.

Figure 1. Cumulative number of pluripotent stem cell (PSC) clinical trials over time (2010-2025).The number of PSC trials is on the rise in 2025, with many trials focusing on ophthalmology, neurology, and oncology. Figure obtained from Kikerby et al. (2025).

What the global PSC clinical trial map looks like in 2025

The PSC clinical trials have currently consolidated around three anchors: the eye, the central nervous system (CNS), and oncology. Ophthalmology is among the leading targets in PSC-based trials. This is because the eye offers local administration, relative immune privilege, and a ready-to-use set of tests that give straightforward answers on therapy effects and impact.

CNS is catching up as delivery and differentiation protocols improve, but durability, tumorigenicity controls, and immunosuppression management remain non-negotiable. Oncology, for non engineered stem cell approaches, is generally less competitive versus engineered immune and gene-modified modalities that can deliver larger effects with cleaner mechanism to endpoint linkages.
Scale is now real. With more than a thousand patients dosed and a vast number of cells administered, regulators are appropriately pressing for trial designs that move beyond safety gating.

FDA authorized trial ≠ FDA approved product

When it comes to clinical trials, there's an important difference between FDA IND authorization and full product approval under a Biologics License Application (BLA). An IND (Investigational New Drug application) lets a company start human trials, but it only takes effect once the FDA allows it-either after 30 days with no objections, or sooner if the FDA gives the green light. Only then can a study be accurately called "FDA-authorized (FDA, 2024 A).

Full approval, on the other hand, requires a BLA after successful trials. A BLA, by contrast, is the FDA's determination that a product is safe, pure, and potent for its intended use and can be marketed-albeit with post-marketing obligations (FDA, 2024 B; FDA 2024 C). Referring to a therapy as an "FDA-approved product" is strictly reserved for those therapies that have received formal marketing approval under a Biologics License from the FDA.

Which FDA-approved stem cell products have been approved lately?

TheFDA's Approved Cellular and Gene Therapy Products list remains curated and selective. It includes multiple cord blood-derived hematopoietic progenitor cell products used for hematopoietic reconstitution, and living constructs that demonstrate the Agency will license complex cellular products when the indication, delivery, and endpoints are airtight (FDA, 2025 D).

Several 2023-2025 approvals are particularly instructive for stem cell operators.

• Omisirge (omidubicel-onlv) - Cord Blood-Derived Hematopoietic Progenitor Cells

  Omisirge received approval on April 17, 2023, for patients (12-65 years) with hematologic malignancies undergoing cord blood transplantation. Omisirge is an allogeneic nicotinamide-modified stem cell graft derived from umbilical cord blood, which accelerates neutrophil recovery and reduces the risk of infection after myeloablative conditioning (FDA, 2023 E; Heo, 2023

• Lyfgenia (lovotibeglogene autotemcel or Lovo-cel)

  Lyfgenia received FDA approval on December 8, 2023, as an autologous cell-based gene therapy for patients aged 12 years and older with sickle cell disease and a history of vaso-occlusive events. This one-time treatment involves collecting and genetically modifying the patient's own hematopoietic stem cells to produce a modified hemoglobin (HbAT87Q), which reduces red blood cell sickling and improves blood flow. In clinical trials, 88% of patients achieved complete resolution of vaso-occlusive events between 6- and 18-months post-treatment. Common adverse reactions included stomatitis, thrombocytopenia, and neutropenia (FDA, 2023 F).

• Ryoncil (remestemcel L rknd)

  Ryoncil received FDA approval on December 18, 2024, as the first MSC therapy for pediatric steroid refractory acute graft versus host disease (SR-aGVHD) in patients aged ≥2 months. This approval represents a significant advance in cell-based therapy as SR-aGVHD is a life-threatening condition seen after allogeneic hematopoietic stem cell transplantation, and treatment options have been extremely limited. Ryoncil utilizes allogeneic bone marrow-derived MSCs from a healthy donor to modulate the immune response and mitigate inflammation associated with SR-aGVHD, providing a critical therapeutic alternative for patients who do not respond to standard steroid treatments (FDA, 2024 G; Kurtzberg, 2025).

Fertilo Receives FDA IND Authorization as First iPSC-Based Therapy in U.S. Phase III

Figure 2. Gameto's Fertilo is entering U.S. Phase III Clinical Trials. Photo courtesy of Gameto (2025).

In February 2025, the FDA granted IND clearance for Fertilo (Figure 2), the first iPSC-based therapy to enter a U.S. Phase III trial. Fertilo uses ovarian support cells (OSCs) derived from REPROCELL's StemRNA™ Clinical Seed iPSCs to support ex vivo oocyte maturation. The Fertilo technology reduces the hormonal burden on patients and has recently resulted in the first live birth (REPROCELL, 2025; BusinessWire, 2025).

Other FDA-authorized clinical trials for novel stem cell therapies

Several stem cell therapies have advanced through FDA clearance in the past year:

OpCT-001

OpCT-001 is an iPSC-derived therapy targeting retinal degeneration, including retinitis pigmentosa and cone-rod dystrophy. In September 2024, OpCT-001 received an FDA clearance of IND application to enter a Phase I/IIa trial to assess safety and visual restoration. This is the first iPSC-based cell therapy to be clinically tested for treating primary photoreceptor diseases (BlueRock Therapeutics, 2024; Kirkeby et al., 2025).

FT819

In April 2025, an off-the-shelf, iPSC-derived CAR T-cell therapy for the treatment of active moderate to severe systemic lupus erythematosus (SLE), including lupus nephritis (LN) was granted an FDA RMAT designation for entering Phase I clinical trial (Fate Therapeutics, 2025).

Neural progenitor cell therapies

Three iPSC-based therapies targeting Parkinson's disease, spinal cord injury, and ALS received FDA IND clearance in June 2025. These off-the-shelf products are designed to address neurodegenerative conditions with scalable, allogeneic cell sources (PR Newswire, 2025).

MyoPAXon

There is an ongoing interventional phase 1 Clinical Trial evaluating MyoPAXon iPSC-derived CD54+ allogeneic muscle progenitor cells in individuals with Duchenne muscular dystrophy (DMD) (ClinicalTrials.gov/NCT06692426).

Autologous iPSC-derived Dopaminergic Neural Progenitor Cells

A Phase I study commenced in late April 2025 for the treatment of Parkinson's Disease. The study uses dopaminergic neural progenitor cells derived from autologous iPSCs (clinicaltrials.gov/NCT06687837).

FT536

An allogeneic, off-the-shelf natural killer (NK) cell therapy, FT536, is produced from a gene-edited clonal master hiPSC line. It is currently in clinical trials for gynecologic cancers (ClinicalTrials.gov/NCT06342986).

These approvals reinforce the clinical momentum of various stem cell platforms and broaden the therapeutic scope beyond oncology and reproductive medicine.

iMSCs Gaining Momentum

iPSC-derived MSCs (iMSCs) offer enhanced consistency, and scalability compared to primary MSCs. While not yet FDA-approved, iMSCs are gaining momentum in regenerative medicine trials targeting conditions such as osteoarthritis and tissue repair (Bloor et al., 2020). There is an ongoing FDA-approved Clinical Trial in the USA for the treatment of High-Risk Acute Graft-Versus-Host Disease (HR-aGvHD) with Cymerus iMSCs (CYP-001), in combination with corticosteroids (clinicaltrials.gov/NCT05643638).

REPROCELL USA: StemRNA™ Clinical iPSC Seed Clones - Submitted FDA DMF

As regulatory review processes grow increasingly lengthy, early regulatory alignment and DMF (Drug Master File)support are essential for efficient trial initiation. In July 2025, REPROCELL submitted a Type II DMFfor its US-generated REPROCELL StemRNA™ Clinical iPSC Seed Clones, providing comprehensive regulatory documentation-including donor screening, GMP-compliant manufacturing, quality control, and raw material sourcing. This DMF allows cell therapy developers to reference REPROCELL's platform in their IND filings while streamlining regulatory submissions for Phase I-III trials (REPROCELL, 2025).

Conclusion

Between 2023 and 2025, a few stem cell therapies have moved decisively from theory to clinical reality. The FDA green-lit Omisirge in April 2023 for faster neutrophil recovery post-cord blood transplant, followed by Lyfgenia in December 2023 for sickle cell disease, and Ryoncil in December 2024 as the first MSC approval for pediatric SR-aGVHD. Meanwhile, PSC trials have scaled globally, over 1,200 patients dosed across ophthalmology, neurology, and oncology, with encouraging safety so far. The FDA also cleared several new iPSC-based programs: OpCT-001 (retinal diseases), FT819 (off-the-shelf CAR-T for lupus, RMAT-designated), plus multiple iPSC-based neural progenitor and muscle progenitor programs-all now authorized to proceed with clinical trials. REPROCELL's StemRNA™ Clinical iPSC Seed Clones supported the development of Fertilo, the first U.S. iPSC-based therapy cleared for Phase III.
These are not just approvals -they are proof that safety, scale, and regulatory momentum align to reshape patient care.

As the regulatory landscape evolves, REPROCELL continues to provide developers with regulatory-compliant clinical-grade iPSCs, iPSC/MSC/iMSC GMP Master Cell Banks (MCB) and Working Cell Banks (WCBs), along with regulatory expertise, and end-to-end support.

References

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