Embedding MSCs in Si-HPMC hydrogel decreased MSC-directed host immune response and increased the regenerative potential of macrophages

查看全文 作　　者：Christelle [1]Demarquay;Lara [1]Moussa;Gildas [2]Réethorée;Fabien [1]Milliat;Pierre [2]Weiss;Noëlle [1]Mathieu

机构地区：[1]Human Health Department,IRSN,French Institute for Radiological Protection and Nuclear Safety,SERAMED,LRMed,Fontenay-aux-Roses 92262,France;[2]Facultéde Chirurgie Dentaire,Regenerative Medicine and Skeleton(RMeS)Laboratory,Universite de Nantes,Nantes 44042,France

出　　处：《Regenerative Biomaterials》索引2022年第9卷第1期,共11页

基　　金：supported by the French‘Agence Nationale pour le Recherche’(Anthos project-ANR13-RPIB-008). 摘　　要：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. 关键词：Si-HPMC hydrogel mesenchymal stromal cells host immune response regenerative medicine

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Embedding MSCs in Si-HPMC hydrogel decreased MSC-directed host immune response and increased the regenerative potential of macrophages

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