A milestone for the therapeutic EV field: FDA approves Ryoncil, an allogeneic bone marrow-derived mesenchymal stromal cell therapy

Abstract

Small extracellular vesicles (sEVs) derived from mesenchymal stromal cells (MSCs) hold substantial promise for therapeutic applications, including immune modulation and tissue regeneration. However, challenges such as batch-to-batch variability, donor material diversity, and the lack of standardized potency testing remain significant barriers to clinical translation. The recent U.S. Food and Drug Administration (FDA) approval of Ryoncil (remestemcel-L) for steroid-refractory acute graft-versus-host disease (aGvHD) in pediatric patients represents a crucial milestone for MSC-based therapies, offering also valuable insights for the development of MSC-EV therapies. This approval highlights the critical need to address variability and standardization issues in MSC products. Strategies like immortalizing MSCs and expanding them clonally can improve scalability, consistency, and overcome limitations inherent to cellular MSC therapies. With the FDA's decision signaling significant progress, optimizing MSC expansion protocols and refining potency testing methods will be crucial for advancing MSC-EVs as a viable therapeutic option, overcoming current challenges, and expanding clinical applications.

Keywords: EVs; Exosomes; extracellular vesicles; mesenchymal stem cells; mesenchymal stromal cells.