Embedding mesenchymal stromal cells(MSCs)in biomaterial is a subject of increasing interest in the field of Regenerative Medicine.Speeding up the clinical use of MSCs is dependent on the use of non-syngeneic models in...Embedding mesenchymal stromal cells(MSCs)in biomaterial is a subject of increasing interest in the field of Regenerative Medicine.Speeding up the clinical use of MSCs is dependent on the use of non-syngeneic models in accordance with Good Manufacturing Practices(GMP)requirements and on costs.To this end,in this study,we analyzed the in vivo host immune response following local injection of silanized hydroxypropyl methylcellulose(Si-HPMC)-embedded human MSCs in a rat model developing colorectal damage induced by ionizing radiation.Plasma and lymphocytes from mesenteric lymph nodes were harvested in addition to colonic tissue.We set up tests,using flow cytometry and a live imaging system,to highlight the response to specific antibodies and measure the cytotoxicity of lymphocytes against injected MSCs.We demonstrated that Si-HPMC protects MSCs from specific antibodies production and from apoptosis by lymphocytes.We also observed that Si-HPMC does not modify innate immune response infiltrate in vivo,and that in vitro co-culture of Si-HPMC-embedded MSCs impacts macrophage inflammatory response depending on the microenvironment but,more importantly,increases the macrophage regenerative response through Wnt-family and VEGF gene expression.This study furthers our understanding of the mechanisms involved,with a view to improving the therapeutic benefits of biomaterial-assisted cell therapy by modulating the host immune response.The decrease in specific immune response against injected MSCs protected by Si-HPMC also opens up new possibilities for allogeneic clinical use.展开更多
基金supported by the French‘Agence Nationale pour le Recherche’(Anthos project-ANR13-RPIB-008).
文摘Embedding mesenchymal stromal cells(MSCs)in biomaterial is a subject of increasing interest in the field of Regenerative Medicine.Speeding up the clinical use of MSCs is dependent on the use of non-syngeneic models in accordance with Good Manufacturing Practices(GMP)requirements and on costs.To this end,in this study,we analyzed the in vivo host immune response following local injection of silanized hydroxypropyl methylcellulose(Si-HPMC)-embedded human MSCs in a rat model developing colorectal damage induced by ionizing radiation.Plasma and lymphocytes from mesenteric lymph nodes were harvested in addition to colonic tissue.We set up tests,using flow cytometry and a live imaging system,to highlight the response to specific antibodies and measure the cytotoxicity of lymphocytes against injected MSCs.We demonstrated that Si-HPMC protects MSCs from specific antibodies production and from apoptosis by lymphocytes.We also observed that Si-HPMC does not modify innate immune response infiltrate in vivo,and that in vitro co-culture of Si-HPMC-embedded MSCs impacts macrophage inflammatory response depending on the microenvironment but,more importantly,increases the macrophage regenerative response through Wnt-family and VEGF gene expression.This study furthers our understanding of the mechanisms involved,with a view to improving the therapeutic benefits of biomaterial-assisted cell therapy by modulating the host immune response.The decrease in specific immune response against injected MSCs protected by Si-HPMC also opens up new possibilities for allogeneic clinical use.
