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Production and Administration of Therapeutic Mesenchymal Stem/Stromal Cell MSC Spheroids Primed in 3-D Cultures Under Xeno-free Conditions
Published on: March 18, 2017
Fate and function of exogenously administered mesenchymal stromal cells: current insights and future directions
Ali Shokoohmand1, Nikita M Patel2, Lorena Braid3
1School of Chemical Engineering, The University of Queensland, Brisbane, Queensland, Australia; Translational Research Institute (TRI), The University of Queensland, Brisbane, Queensland, Australia.
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 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.
Insights
Understanding mesenchymal stromal cells (MSCs) in vivo is crucial for regenerative medicine. This expert review identifies key research questions on MSC fate, immune interactions, and persistence to improve cell-based therapies.
Area of Science:
- Regenerative Medicine
- Cell Biology
- Immunology
Background:
- The in vivo behavior of mesenchymal stromal cells (MSCs), including their clearance and tissue interactions after administration, is not fully understood.
- Mechanisms like inflammation, coagulation, complement activation, apoptosis, and efferocytosis contribute to MSC clearance, but their precise roles in MSC function and efficacy require further investigation.
Purpose of the Study:
- To address critical knowledge gaps regarding the in vivo fate and function of MSCs.
- To define key unanswered questions and propose experimental strategies for studying MSCs in clinical settings.
Main Methods:
- Convened an international expert panel to review existing evidence on MSC biology and clinical applications.
- Structured discussions around MSC biodistribution, mechanisms of action, local administration implications, and persistence/clearance dynamics.
- Focused on the role of MSC apoptosis and its immunological consequences, including interactions with phagocytes and endothelial barriers.
Main Results:
- Identified urgent research questions concerning MSC biodistribution, immune modulation, and the impact of delivery context.
- Highlighted the need to move beyond traditional cell tracking to functional persistence assessments.
- Emphasized the importance of understanding MSC apoptosis and its immunological interactions.
Conclusions:
- Further research is essential to elucidate MSC behavior in vivo.
- Addressing identified knowledge gaps will facilitate the development of safer and more effective MSC-based therapies.
- A deeper understanding of MSC clearance and persistence mechanisms is critical for optimizing regenerative medicine strategies.
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