The rise of iPSC-derived mesenchymal stem cells (iMSCs) represents a significant evolution in regenerative medicine. iMSCs are generated by reprogramming adult somatic cells, typically fibroblasts, into induced pluripotent stem cells (iPSCs), which are then differentiated into mesenchymal stem cells (MSCs). This breakthrough technology offers several advantages over traditional MSC therapies, which are often derived from limited, patient-specific sources such as bone marrow or adipose tissue.
iMSCs provide a potentially infinite and more consistent cell source, bypassing issues related to donor variability, immune rejection, and the challenges of obtaining autologous cells. Additionally, iMSCs have the potential to be produced at low cost. Altogether, iMSCs represents a powerful combination of advantages and a much needed solution to traditional stem cell manufacturing challenges.
The Rise of iMSCs
In recent years, several biotechnology companies have embraced iMSCs for developing novel therapeutics, capitalizing on their regenerative and immunomodulatory properties. By leveraging gene editing and advanced differentiation techniques, iMSCs are being optimized for use in a wide range of applications, including tissue repair, autoimmune diseases, and even cancer therapies.
Their potential for scalability, coupled with advancements in genetic engineering, promises to address the supply limitations that have hindered the broader use of conventional MSCs. These developments pave the way for more accessible, off-the-shelf cell therapies that could significantly enhance patient outcomes across multiple therapeutic areas.
Today, an impressive number of market competitors are developing iPSC-derived MSC products, including:
1. Cynata Therapeutics (Australia)
Cynata Therapeutics is pioneering its Cymerus™ platform, which uses iPSCs to generate mesenchymoangioblasts as precursors for MSC production. This allows for the creation of consistent, scalable, clinical-grade MSC products. This platform uniquely enables the scalable production of consistent, high-quality MSCs, which are derived from a single donor and cell bank, overcoming many challenges seen with traditional MSC manufacturing methods. The Cymerus™ platform’s ability to generate an effectively limitless supply of MSCs from a single iPSC source makes it a compelling and cost-effective solution for addressing the issues common with other MSC therapies.
Cynata has several clinical-stage candidates under development, including CYP-001, CYP-002, CYP-004, and CYP-006TK. Cynata is currently undertaking clinical trials for indications that include acute GvHD, critical limb ischemia (CLI), COVID-19, diabetic foot ulcers (DFUs), and osteoarthritis (OA).
Cynata set two world firsts in 2020 when it launched the world’s first clinical trial involving an iPSC-derived cell therapeutic product to enter Phase 3. This trial was also the largest trial ever conducted with an iPSC-derived cellular therapeutic with an enrollment of 440 patients.
More recently in December 2024, Cynata announced that CYP-006TK—its iPSC-derived MSC topical wound dressing product composed of MSCs seeded onto a novel silicone dressing—achieved both safety and efficacy in its Phase I trial for the treatment of diabetic foot ulcers (DFUs).
2. Eterna Therapeutics (Brooklyn, NY)
Eterna Therapeutics is developing ERNA-101, an innovative cell therapy based on induced pluripotent stem cells (iPSCs) differentiated into mesenchymal stem cells (iMSCs). This therapy is designed to target advanced solid tumors such as triple-negative breast cancer and platinum-resistant, TP53-mutant ovarian cancer. ERNA-101 works by delivering pro-inflammatory cytokines IL-7 and IL-15 directly to the tumor microenvironment, aiming to boost antitumor immunity. The therapy is currently in preclinical stages, with plans to advance towards IND-enabling studies and regulatory submissions by 2026.
3. Implant Therapeutics (Syracuse, NY)
Implant Therapeutics, a subsidiary of panCELLa, is developing innovative hypo-immunogenic iPSC-derived mesenchymal stem cells (MSCs) by integrating panCELLa’s proprietary technologies—FailSafe™ and iACT Stealth Cell™. These technologies enable the creation of MSCs that are immune-evasive, enhancing their potential as therapeutic candidates for bone, cartilage, and tendon repair. The hypo-immunogenic properties allow these cells to overcome immune rejection issues commonly associated with allogeneic therapies, positioning them as a more viable alternative for tissue regeneration and ex-vivo gene therapy applications.
Through a strategic partnership with RxCell, Implant Therapeutics is advancing its platform with access to cGMP-grade iPSC lines and the ability to generate a broad range of therapeutic-grade MSC products. This collaboration aims to accelerate the development of these advanced MSCs, enhancing their consistency and efficacy. The combination of iPSC-derived MSCs with the FailSafe™ and iACT Stealth Cell™ technologies provides a next-generation approach to regenerative medicine by offering “off-the-shelf” solutions that can be universally applied in clinical settings, without the need for donor matching.
4. Bone Therapeutics (Belgium)
Bone Therapeutics is focused on developing advanced cell therapies for orthopedic and bone-related conditions. It has partnered with Implant Therapeutics to incorporate iPSC-derived MSCs into its allogeneic therapy pipeline (iMSCs). This collaboration enhances the scalability and consistency of Bone Therapeutics’ products, addressing key challenges in manufacturing traditional MSC therapies. Bone Therapeutics’ primary platform centers around ALLOB, an allogeneic cell therapy that uses MSCs to promote bone regeneration. The integration of iPSC-derived MSCs through Implant Therapeutics’ expertise aims to improve the uniformity and therapeutic potential of ALLOB, while enabling larger-scale production for a broader patient base.
4. Brooklyn ImmunoTherapeutics (Cambridge, MA)
Brooklyn Immuno Therapeutics is advancing the development of a set of mesenchymal stem cell (MSC) products derived from induced pluripotent stem cells (iPSCs), incorporating cutting-edge gene editing technologies. The company is exploring the potential of these engineered MSCs in treating a variety of medical conditions, including cancer, blood disorders, and genetic diseases. Brooklyn’s gene editing platform leverages proprietary technologies like mRNA-based reprogramming and advanced lipid nanoparticle (LNP) delivery methods to optimize cellular therapies. With an extensive patent portfolio, including over 70 issued patents related to MSCs and gene editing, Brooklyn is positioning itself as a leader in regenerative medicine.
In addition to its gene editing expertise, Brooklyn is exploring the therapeutic applications of its iPSC-derived MSCs for multiple disease indications. This includes preclinical and clinical-stage efforts in oncology, with its lead product, IRX-2, a cytokine-based therapy, currently in Phase 2B trials for head and neck cance.
5. Fujifilm CDI (Madison, WI)
Fujifilm CDI (FCDI) is a prominent leader in the development and manufacturing of human induced pluripotent stem cells (iPSCs). Its provides GMP-grade iPSCs for collaborations focused on cell therapy applications and has licensed its iPSC technology to leading biotech companies that include Cynata Therapeutics, Sana Biotechnology, and Lonza. Fujifilm currently own a 5.8% ownership stake in Cynata Therapeutics, which is manufacturing iMSCs via its Cymerus™ platform. This collaboration leverages FCDI’s expertise in iPSC technology and manufacturing capabilities to order to support Cynata’s extensive preclinical and clinical operations.
In September 2021, Cynata and FUJIFILM Corporation entered into an updated strategic partnership agreement outlining core terms for FCDI to provide clinical and commercial manufacturing services for Cynata’s Cymerus™-derived iMSC products. The agreement includes activities related to technology transfer, process validation, and manufacturing. FCDI’s role in this partnership includes establishing the current manufacturing process at its facilities, initially replicating the process used by Cynata’s existing contract manufacturer, Waisman Biomanufacturing.
Additionally, FCDI’s investment in a new cGMP-compliant production facility in Madison, Wisconsin (operational since March 2020) underscores its commitment to acting as a CDMO for a diverse range of iPSC products.
6. Citius Pharmaceuticals (Cranford, NJ)
Citius Pharmaceuticals has developed a cutting-edge platform for generating induced mesenchymal stem cells (i-MSCs) from a single-donor dermal fibroblast using proprietary, non-viral, mRNA-based reprogramming technology. This approach enables the creation of a clonal Master Cell Bank under cGMP conditions, ensuring consistency, scalability, and genetic uniformity in cell production. The i-MSCs exhibit enhanced immunomodulatory potency and viability compared to adult-donor-derived MSCs and are designed for allogeneic applications.
Citius is leveraging this technology to address acute respiratory distress syndrome (ARDS), including cases arising from COVID-19. In preclinical studies, their i-MSCs demonstrated the potential to reduce pulmonary inflammation and improve key clinical outcomes.
8. Kiji Therapeutics (Paris, France)
Kiji Therapeutics was established in 2023 with a seed investment from VC firm AdBio Partners to develop engineered iPSC-derived MSCs. Its first pre-clinical products are adipose derived MSCs transduced with with IL10 and CXCR4, key molecules involved in modulating immune responses and improving cell homing. These products are designed for use in conditions like inflammatory and autoimmune diseases, where the cells’ immunomodulatory properties can offer significant therapeutic benefit. With research and development facilities in Spain, Kiji is poised to bring its lead product to clinical trials.
