Fate and function of exogenously administered mesenchymal stromal cells : current insights and future directions
(2026) In Cytotherapy 28(2).- 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, activation of coagulation and complement pathways, 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 experts in MSC biology and clinical regenerative medicine convened to assess current evidence and define key unanswered questions. Discussions were structured... (More)
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, activation of coagulation and complement pathways, 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 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: (i) biodistribution and mechanisms of action following systemic delivery; (ii) biological implications of local or depot-based administration and (iii) 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 MSC behavior in vivo and guide the development of safer, more predictable and more effective MSC-based interventions.
(Less)
- author
- Shokoohmand, Ali
; Patel, Nikita M.
; Braid, Lorena
; Dominici, Massimo
; Heng, Tracy S.P.
; Ankrum, James A.
; Barua, Jayita
; Caicedo, Andrés
; Creane, Michael
; Davies, Lindsay
; dos Santos, Claudia C.
; Enes, Sara Rolandsson
LU
; English, Karen
; Farge, Dominique
; Fernández-García, María
; Galipeau, Jacques
; Kadri, Nadir
; Khoury, Maroun
; Kilfeather, Stephen
; Krampera, Mauro
; Krasnodembskaya, Anna
; Lalu, Manoj
; Blanc, Katarina Le
; Moll, Guido
; Nolta, Jan
; O'Kane, Cecilia
; Rocco, Patricia R.M.
; Shi, Yufang
; Weiss, Daniel J.
and Viswanathan, Sowmya
(Less) - organization
- publishing date
- 2026-02
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- apoptosis, extracellular vesicles, immune cells, instant blood-mediated inflammatory reaction, local delivery, mechanism of action, MSCs, persistence, systemic delivery
- in
- Cytotherapy
- volume
- 28
- issue
- 2
- article number
- 102007
- publisher
- Taylor & Francis
- external identifiers
-
- scopus:105025538726
- pmid:41420629
- ISSN
- 1465-3249
- DOI
- 10.1016/j.jcyt.2025.102007
- language
- English
- LU publication?
- yes
- id
- a8d9e251-5955-4ab0-959b-7d59ba0e3b7f
- date added to LUP
- 2026-02-26 13:52:40
- date last changed
- 2026-07-04 12:16:26
@article{a8d9e251-5955-4ab0-959b-7d59ba0e3b7f,
abstract = {{<p>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, activation of coagulation and complement pathways, 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 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: (i) biodistribution and mechanisms of action following systemic delivery; (ii) biological implications of local or depot-based administration and (iii) 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 MSC behavior in vivo and guide the development of safer, more predictable and more effective MSC-based interventions.</p>}},
author = {{Shokoohmand, Ali and Patel, Nikita M. and Braid, Lorena and Dominici, Massimo and Heng, Tracy S.P. and Ankrum, James A. and Barua, Jayita and Caicedo, Andrés and Creane, Michael and Davies, Lindsay and dos Santos, Claudia C. and Enes, Sara Rolandsson and English, Karen and Farge, Dominique and Fernández-García, María and Galipeau, Jacques and Kadri, Nadir and Khoury, Maroun and Kilfeather, Stephen and Krampera, Mauro and Krasnodembskaya, Anna and Lalu, Manoj and Blanc, Katarina Le and Moll, Guido and Nolta, Jan and O'Kane, Cecilia and Rocco, Patricia R.M. and Shi, Yufang and Weiss, Daniel J. and Viswanathan, Sowmya}},
issn = {{1465-3249}},
keywords = {{apoptosis; extracellular vesicles; immune cells; instant blood-mediated inflammatory reaction; local delivery; mechanism of action; MSCs; persistence; systemic delivery}},
language = {{eng}},
number = {{2}},
publisher = {{Taylor & Francis}},
series = {{Cytotherapy}},
title = {{Fate and function of exogenously administered mesenchymal stromal cells : current insights and future directions}},
url = {{http://dx.doi.org/10.1016/j.jcyt.2025.102007}},
doi = {{10.1016/j.jcyt.2025.102007}},
volume = {{28}},
year = {{2026}},
}