Roles of microglia/macrophage and antibody in cell sheet transplantation in the central nervous system

Abstract

Background We previously established a human mesenchymal stem cell (MSC) line that was modified to express trophic factors. Transplanting a cell sheet produced from this line in an amyotrophic lateral sclerosis mouse model showed a beneficial trend for mouse life spans. However, the sheet survived for less than 14 days, and numerous microglia and macrophages were observed within and adjacent to the sheet. Here, we examined the roles of microglia and macrophages as well as acquired antibodies in cell sheet transplantation. Methods We observed the effects of several MSC lines on macrophages in vitro, that is, phenotype polarization (M1 or M2) and migration. We then investigated how phenotypic polarization affected MSC survival using antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (ADCP). We also confirmed the role of complement on cytotoxicity. Lastly, we selectively eliminated microglia and macrophages in vivo to determine whether these cells were cytoprotective to the donor sheet. Results In vitro co-culture with MSCs induced M2 polarization in macrophages and facilitated their migration toward MSCs in vitro. There was no difference between M1 and M2 phenotypes on ADCC and ADCP. Cytotoxicity was observed even in the absence of complement. Eliminating microglia/macrophage populations in vivo resulted in increased survival of donor cells after transplantation. Conclusions Acquired antibodies played a role in ADCC and ADCP. MSCs induced M2 polarization in macrophages and facilitated their migration toward MSCs in vitro. Despite these favorable characteristics of microglia and macrophages, deletion of these cells was advantageous for the survival of donor cells in vivo.

Macrophage/microglia polarization for the treatment of diabetic retinopathy

“…Due to a decline in M1 markers and a raise in M2 markers, paracrine signaling of hMSC altered the microglial phenotype and the production of anti-inflammatory proteins in the retina ( 164 ). In neurological studies, MSCs have been found to induce M2 polarization in macrophages and facilitate their migration into MSCs in vitro ( 165 ). Therefore, it is conceivable that injecting MSCs into the vitreous cavity may be a potential therapeutic approach for treating DR since it may increase the number of microglia with anti-inflammatory phenotypes and help preserve the retina.…”