Distinct in vitro properties of embryonic and extraembryonic fibroblast-like cells are reflected in their in vivo behavior following grafting in the adult mouse brain

Although intracerebral transplantation of various fibroblast(-like) cell populations has been shown feasible, little is known about the actual in vivo remodeling of these cellular grafts and their environment. In this study, we aimed to compare the in vitro and in vivo behavior of two phenotypically similar but developmentally distinct fibroblast-like cell populations, namely, mouse embryonic fibroblasts (mEFs) and mouse fetal membrane-derived stromal cells (mFMSCs). While both mEFs and mFMSCs are readily able to reduce TNF-alpha secretion by LPS/IFN-gamma-activated BV-2 microglia, mFMSCs and mEFs display strikingly opposite behavior with regard to VEGF production under normal and inflammatory conditions. Whereas mFMSCs downregulate VEGF production upon coculture with LPS/IFN-gamma-activated BV-2 microglia, mEFs upregulate VEGF production in the presence of LPS/IFN-gamma-activated BV-2 microglia. Subsequently, in vivo grafting of mFMSCs and IDEFs revealed no difference in microglial and astroglial responses toward the cellular grafts. However, mFMSC grafts displayed a lower degree of neoangiogenesis 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. This work was supported by research grants G.0136.11 and G.0130.11 (granted to Z.B. and P.P.) of the Fund for Scientific Research-Flanders (FWO-Vlaanderen, Belgium) and in part by a Methusalem research grant from the Flemish government (granted to Z.B. and H.G.). Nathalie De Vocht and Chloe Hoornaert hold a Ph.D.-studentship from the FWO-Vlaanderen. Debbie Le Blon holds a Ph.D.-studentship from the Flemish Institute for Science and Technology (IWT). The authors declare no conflicts of interest.