The composite biomatrix SC/CM improved the therapeutic effects of xenogeneic MSC on wound healing in immune-competent mice via immune niche reprogramming

Allogenic mesenchymal stem cell (allo-MSC) transplantation has shown great potential in the field of tissue repair. Increasing evidence has shown that allo-MSC are not completely immune-privileged; the immunogenic response after transplantation is involved in the poor survival and limited therapeutic effects of allo-MSC therapy. Here, we developed a composite biomatrix of a chondroitin sulfate/collagen scaffold (SC) loaded with conditioned medium (CM) derived from adipose mesenchymal cells and showed that SC/CM could significantly promote the survival of xenogeneic human MSC after engraftment in an immune-competent mouse wound model. The local immune niche, including the release of inflammatory cytokines and macrophage polarization, is also improved in engrafted wounds. Accordingly, the wound healing effects of MSC, including myofibroblast activation and collagen production, were most remarkable when they were coengrafted with the composite biomatrix SC/CM. Overall, the composite biomatrix SC/CM offered a novel strategy for the application of allo- or even xeno-MSC therapy in wound healing, and the exploration of the mechanism will further expand our understanding of the immunogenicity of MSC.