Exploring the benefits of iPSC, MSC and iMSC therapies: from clinical breakthroughs to the future of regenerative medicine.
The use of stem cells – including induced pluripotent stem cells (iPS or iPSCs) and mesenchymal stem cells (MSCs) – has been instrumental for the development of pioneering therapeutic solution and transformation of regenerative medicine. Their ability to self-renew and differentiate into specialized cell types opens access to new treatments for diseases with limited options. Recently, numerous clinical trials have explored stem cell-based therapies for conditions ranging from vision loss to heart failure (1,2).
The benefits of stem cell-based therapy
What does stem cell therapy do that conventional medicine cannot? Stem cells are changing the development of personalized medicine by offering a significant advantage to conventional treatments: functional regeneration in a patient-specific way. Unlike traditional drug therapies that merely manage symptoms, stem cell-based approaches have the power to repair, replace, and restore damaged tissues, potentially curing previously intractable diseases (3).
By their ability to regenerate lost or damaged cells, stem cell-based approaches have helped restore eyesight in patients with macular degeneration and regenerate heart muscle after a heart attack. Additionally, MSCs have demonstrated remarkable efficacy in reducing inflammation, particularly in conditions such as graft-versus-host disease (GVHD), where conventional immunosuppressants are often ineffective (1,2).
Rising attention on iPSCs and MSCs in therapy
Once discussed mostly in academic circles, these cell types are now among the hottest topics at recent industry events, such as the International Society for Cell & Gene Therapy (ISCT) Annual Meeting 2025 and the ASCGT in New Orleans.
At these events, conversations have shifted from purely scientific questions to broader considerations of clinical applicability and scalable manufacturing. “ASGCT 2025 was a powerful reminder that gene therapy is no longer just a frontier of scientific discovery — it’s a field rapidly evolving toward real-world impact,” remarked one panelist at ISCT (4). MSCs, with their immunomodulatory properties, are being positioned as a near-term option for inflammatory and autoimmune disorders, while iPSCs are celebrated for their versatility in generating virtually any cell type (5).
The manufacturing industry is responding to this momentum, with companies accelerating the development of standardized, GMP-compliant production pipelines to ensure quality, reproducibility, and cost-efficiency. As one industry expert summarized: “What resonated most was the shared sense of urgency and purpose. The science is moving fast, but so is the commitment to making these therapies matter — not just in theory, but in practice, and in patients’ lives” (4).
iPSC are transforming therapy
While no iPSC-based therapy has yet been fully approved, numerous clinical trials are underway. Among the early applications of iPSCs are eye diseases: In Japan, the first iPSC trial transplanted iPS-derived retinal pigment epithelium (RPE) cells into a patient with age-related macular degeneration, resulting in improved vision (6). In the realm of neurological applications, a trial using iPS-derived neural progenitor cells for spinal cord injury was approved in 2018 at Keio University (Japan) (7). For cardiac conditions, trials are exploring iPSC-derived heart muscle cells for heart failure, including engineered heart tissue patches to repair damaged heart tissue (8).
Emerging uses for iPSCs include generating mesenchymal cells for treating graft-versus-host disease (GVHD) (9). Biotech companies are developing “off-the-shelf” iPS-based cell products such as clonal iPS-derived immune cells for cancer therapy (10). Although iPSC therapies are still experimental, early studies have shown promising results in integrating these cells and improving tissue function (1).
First approvals of MSC therapy
MSC-based treatments represent the first stem cell therapies to reach the clinic, playing an important role in conditions that are unresponsive to standard treatments. Importantly, MSC therapy for steroid-refractory acute GVHD in children received conditional approval in Canada in 2012. Prochymal (an allogeneic bone marrow–derived MSC product) received conditional approval from Health Canada in 2012 for pediatric acute GVHD, marking the first-ever approved stem cell drug (11). Japan approved a similar MSC product (Temcell) for GVHD in 2015, however nearly half of the patients did not respond to the therapy (12). More recently, in December 2024, Remestemcel-L was licensed as Ryoncil and became the first MSC therapy approved by the U.S. FDA (13). Another landmark approval was Alofisel (Darvadstrocel), an allogeneic adipose-derived MSC therapy that was approved in 2018 in Europe and Japan for complex perianal fistulas in Crohn’s disease (14), but was taken from the EU market in December 2024 (15).
MSCs are being evaluated for a variety of conditions, including osteoarthritis, systemic lupus, multiple sclerosis, and orthopedics. Trials in stroke and spinal cord injury aim to evaluate MSCs’ neurotrophic and anti-inflammatory effects to aid recovery. Clinical studies generally show that MSC therapies are safe and well-tolerated, with some reporting meaningful improvements (11).
The special case of iMSCs
An emerging approach combines the advantages of both iPSCs and MSCs through iPSC-derived mesenchymal stromal cells (iMSCs). These cells offer a potentially unlimited and standardized source of MSCs, overcoming the donor variability and limited expansion potential of primary MSCs. iMSC-based therapies are now in clinical evaluation, although none have been approved to date.
For example, Citius Pharmaceuticals has developed an mRNA-based, non-viral platform to generate iMSCs under cGMP, demonstrating enhanced potency in reducing lung inflammation in ARDS models. Additionally, engineered iMSCs (e.g., Kiji Therapeutics’ IL‑10/CXCR4‐enhanced cells) are advancing toward clinical evaluation for autoimmune and inflammatory diseases (16).
In terms of therapeutic impact, iMSC-derived extracellular vesicles (EVs) have shown efficacy in wound healing, cardiovascular repair, and renal fibrosis in animal models (17). In Sjögren’s syndrome, a chronic autoimmune disorder focused on moisture-producing glands, NOD mouse models have shown that iMSC EVs matched the immunomodulatory effects of bone marrow MSCs (18).
This emerging field addresses production bottlenecks and functional variability, placing iMSCs firmly on track to become standardized, allogeneic MSC therapies with substantial translational promise.
Looking ahead, stem cell therapy is moving toward next-generation therapies, including gene-edited stem cells and bioengineered tissues. With recent FDA approvals for MSC-based treatments and promising clinical trials for iPSC-derived therapies, the future of personalized regenerative medicine is closer than ever. Importantly, the ability to efficiently culture and expand these stem cell types and next-generation therapies in a cost-effective manner, while maintaining GMP standards, will be critical for their translation into widespread clinical use. Innovative, resource-efficient expansion systems, such as Green Elephant Biotech’s compact, scalable platform CellScrew®, are helping produce clinically relevant cell quantities and bridge the gap between basic research and clinical application.
References
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(2) Scudellari M. How iPS cells changed the world. Nature. 2016 Jun 16;534(7607):310-2. doi: 10.1038/534310a. PMID: 27306170.
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(7) Keio University, World’s First Regenerative Therapy for Spinal Cord Injury Using iPS Cells, May 31 2022, Keio Times, available from https://www.keio.ac.jp/en/keio-times/features/2022/4/
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(13) U.S. Food & Drug Administration, FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease, December 18, 2024, available from https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host
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