Distinct in vitro properties of embryonic and extra-embryonic fibroblast-like cells are reflected in their in vivo behaviour following grafting in the adult mouse brain
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
Cell transplantation. - Amsterdam
, p. 223-233
University of Antwerp
Although intracerebral transplantation of various fibroblast (-like) cell populations has been shown feasible, little is known about the actual in vivo remodelling of these cellular grafts and their environment. In this study, we aimed to compare the in vitro and in vivo behaviour of two phenotypically similar ‐ but developmentally distinct ‐ fibroblast‐like cell populations, namely mouse embryonic fibroblasts (mEF) and mouse foetal membrane‐derived stromal cells (mFMSC). While both mEF and mFMSC are readily able to reduce TNFα secretion by LPS/IFNγ‐activated BV2 microglia, mFMSC and mEF display a strikingly opposite behaviour with regard to VEGF production under normal and inflammatory conditions. Whereas mFMSC downregulate VEGF production upon co‐culture with LPS/IFNγ‐activated BV2 microglia, mEF upregulate VEGF production in the presence of LPS/IFNγ‐activated BV2 microglia. Subsequently, in vivo grafting of mFMSC and mEF revealed no difference in microglial and astroglial responses towards the cellular grafts. However, mFMSC grafts displayed a lower degree of neo‐angiogenesis as compared to mEF grafts, thereby potentially explaining the lower cell number able to survive in mFMSC grafts. In summary, our results suggest that physiological differences between fibroblast‐like cell populations might lie at the basis of variations in histopathological and/or clinical outcome following cell grafting in mouse brain.