Abstract
Recent regulatory approvals and maturing clinical evidence indicate that mesenchymal stromal cells (MSCs) exert therapeutic effects predominantly through paracrine and immunomodulatory mechanisms rather than lineage-driven regeneration. In line with contemporary positions from International Society for Cell & Gene Therapy and Japanese Society for Regenerative Medicine, we argue for mechanism-aligned terminology and propose framing these interventions as MSC-based immunomodulatory therapies. This terminology improves scientific clarity, aligns clinical endpoints and potency assays with the mechanism of action, facilitates coherent regulatory communication, and mitigates public misunderstanding tied to the legacy “stem cell” label.
The development trajectory of mesenchymal stromal cell (MSC)-based products has reached a notable inflection. Canada authorized remestemcel-L for pediatric acute graft-versus-host disease (aGVHD) in 2012, marking an early milestone 1 . In December 2024, the U.S. Food and Drug Administration–approved remestemcel-L-rknd (Ryoncil) for steroid-refractory pediatric aGVHD—the first MSC product approved in the United States2,3. In January 2025, China’s National Medical Products Administration granted conditional approval for Amimestrocel injection (Ruibosheng) for steroid-refractory aGVHD with predominant gastrointestinal involvement in patients aged ≥14 years. Together, these decisions across major jurisdictions signal maturation of the therapeutic class and sharpen the need to align nomenclature with mechanism and evaluation standards.
Despite progress, terminology still lags behind biology. The legacy term “mesenchymal stem cells” stems from in vitro clonogenicity and multipotency, yet converging in vivo evidence supports a primarily paracrine and immunoregulatory mode of action4,5. Reflecting this, the International Society for Cell & Gene Therapy (ISCT) recommended “mesenchymal stromal cells (MSCs)” in 2019, retaining the MSC acronym while aligning with in vivo properties 6 . In 2025, the ISCT MSC Committee further emphasized immunomodulatory criteria, mechanism-aligned potency assays, and explicit framing as cell therapies 3 . The Japanese Society for Regenerative Medicine (JSRM) likewise recommends “mesenchymal stromal cells,” underscoring international convergence on mechanism-accurate terminology 7 . The evolution of MSC nomenclature—from “stem” to “stromal” to more descriptive, mechanism-based terminology—reflects a maturation of the field and aligns terminology with biological function and clinical application. Against this backdrop, we advocate a mechanism-aligned, communication-ready designation—MSC-based immunomodulatory therapy—to enhance clarity in science, clinical practice, and regulation.
Current clinical applications and mechanism
MSCs are among the most intensively studied adult cell types in regenerative medicine and immunotherapy. Across immune‑mediated indications, including aGVHD 8 , Crohn’s disease 9 , and autoimmune disorders such as multiple sclerosis, systemic lupus erythematosus, type 1 diabetes, and rheumatoid arthritis10–13, clinical and translational data increasingly indicate benefits arise from immunomodulation rather than lineage-driven regeneration. Mechanistically, via paracrine factors and extracellular vesicles, MSCs suppress effector and alloreactive T-cell activation while expanding regulatory T cells (Tregs); downregulate proinflammatory cytokines (e.g., IL-1β, TNF-α, IL-6, IL-17A) and promote anti-inflammatory mediators (e.g., IL-10, TGF-β); inhibit dendritic cell maturation and modulate B-cell activation, reducing autoreactivity; reprogram myeloid cells toward inflammation-resolving phenotypes5,14. Despite heterogeneity in cell source, dose, and route, these convergent signals support the view that MSCs act predominantly as immune modulators in vivo. Consistent with this, professional societies recommend the “mesenchymal stromal cell” designation and emphasize immunomodulatory properties to improve clarity for scientific, clinical, and regulatory evaluation3,15.
Potential issues and advanced therapy medicinal products context
The persistence of the generic “stem cell” label fosters regeneration‑centric expectations and is susceptible to misuse by unregulated providers5,16–18. Mechanism‑aligned terminology is corrective, not cosmetic, by improving informed consent and reducing ambiguity in public discourse. In many jurisdictions, MSC products are regulated as advanced therapy medicinal products (ATMPs) or analogous biologics, with evaluation spanning chemistry‑manufacturing‑controls (CMC), nonclinical, clinical, and post‑marketing phases. Explicitly articulating the immunomodulatory mechanism sharpens endpoint selection, potency‑assay design, and benefit–risk appraisal in line with contemporary guidance, without diminishing scrutiny. We suggest an optional, mechanism‑explicit designation for communication and educational contexts: “mesenchymal stromal cell‑based immunomodulatory therapy” (also referred to as “mesenchymal immunomodulatory therapy”). This preserves the familiar MSC root, reflects ISCT/JSRM usage of “stromal,” and situates these products squarely as cell therapies3,7,15. By centering immunomodulation, the term clarifies therapeutic intent, aligns trial design with mechanism, and differentiates these ATMPs from regeneration‑centric narratives.
Anticipated benefits of mechanism-aligned nomenclature
Aligning terminology with scientific consensus and core mechanism enhances coherence across research, practice, and regulation. Current evidence shows that MSC clinical effects are predominantly paracrine and immunoregulatory, consistent with ISCT 2019 and ISCT 2025 framings of approved MSC products as cell therapies, and with JSRM’s adoption of “stromal” terminology3,6,7. Using mechanism‑explicit language, positioning MSCs as immunomodulatory cell therapies that recalibrate T‑cell and myeloid responses 5 clarifies therapeutic intent, improves patient understanding and expectation alignment, and supports indication‑appropriate, immunology‑anchored outcomes. Mechanism‑accurate naming promotes alignment among product classification, potency assays, and endpoints centered on immunomodulation, strengthening cross‑disciplinary communication from development through post‑approval monitoring. Reducing reliance on the generic “stem cell” label helps counter marketing misuse, enhances public discernment, and safeguards the credibility of evidence‑based MSC therapies.
A timely opportunity
The recent approvals of remestemcel‑L-rknd (Ryoncil) and Amimestrocel injection, together with accumulating evidence across immune‑mediated diseases, create a timely opportunity to harmonize nomenclature with current science. As MSC products progress through regulatory pathways, adopting terminology that explicitly integrates their immunomodulatory mechanism and status as cell therapies can enhance coherence across research, clinical practice, and policy, clarifying intent, aligning endpoints and potency assays, and strengthening communication from development through post‑approval use.
Conclusion
Precise, mechanism-aligned nomenclature is essential for the responsible development and communication of MSC-based therapies. Framing these interventions as MSC-based immunomodulatory therapies reflects their predominant clinical action, improves clarity for patients and clinicians, and aligns with contemporary scientific, regulatory, and ethical guidance. By adopting mechanism-explicit terminology, the field can more accurately represent which MSC therapies demonstrably are tools for immune recalibration and inflammation control, while avoiding the overpromissory connotations historically attached to the generic term “stem cell.” In my view, this terminological shift is not merely semantic but is fundamental to the responsible translation of MSC therapies. This refinement reflects the field’s maturation and aligns terminology with mechanism-driven evaluation and regulatory standards. It clarifies their identity for clinicians, sets realistic expectations for patients, and provides a more accurate framework for regulators. I hope this perspective stimulates further discussion within the field on the importance of precise nomenclature.
Footnotes
Ethical approval
Not applicable.
Statement of human and animal rights
This article does not contain any studies with human or animal subjects.
Statement of informed consent
There are no human subjects in this article and informed consent is not applicable.
Author contributions
Qianfa Long is the sole author and is responsible for all aspects of this manuscript.
Funding
The author received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.