Logo image
Fate and Function of Exogenously Administered MSCs: Current Insights and Future Directions
Journal article   Peer reviewed

Fate and Function of Exogenously Administered MSCs: Current Insights and Future Directions

Ali Shokoohmand, Nikita M Patel, Lorena Braid, Massimo Dominici, Tracy S.P. Heng, James A. Ankrum, Jayita Barua, Andrés Caicedo, Michael Creane, Lindsay Davies, …
Cytotherapy (Oxford, England), Vol.28(2), 102007
02/2026
DOI: 10.1016/j.jcyt.2025.102007
PMID: 41420629

View Online

Abstract

The in vivo fate of mesenchymal stromal cells (MSCs), including their clearance, interaction with host tissues, and persistence, remains incompletely understood following systemic or local clinical administration to patients. Although immune-mediated clearance mechanisms, such as triggering of the instant blood-mediated inflammatory reaction (IBMIR), coagulation and complement pathways activation, apoptosis, and efferocytosis have been identified, their contributions to MSC function and efficacy are still under investigation. To address these knowledge gaps, an international panel of global experts in MSC biology and clinical regenerative medicine convened to assess current evidence and define key unanswered questions. Discussions were structured around three thematic domains: (1) biodistribution and mechanisms following systemic delivery; (2) biological implications of local or depot-based administration, and (3) the dynamics of MSC persistence and clearance in vivo. A major focus was on the role of MSC apoptosis and its immunological consequences, particularly interactions between apoptotic MSCs, phagocytes, and endothelial barriers. This perspective highlights the most urgent research questions identified during the meeting and in follow-up discussions and proposes experimental strategies to move beyond traditional cell tracking toward interrogating functional persistence, immune modulation, and delivery context. Addressing these gaps will deepen our understanding of MSCs in vivo and guide the development of safer, predictable, and effective MSC-based interventions.
Apoptosis Extracellular vesicles immune cells instant blood-mediated inflammatory reaction local delivery mechanism of action MSCs persistence systemic delivery

Details

Logo image