In vivo Ontogeny of human forebrain neural progenitor cell grafts in adult rats: an immunohistological study

Abstract

A thorough understanding of the cell behaviors of the human neural grafts is fundamental to exploit them to achieve cell therapy for recovering brain functions. Here by using immunohistological staining, we trace the cell fate of the intrastriatal human neural progenitor cell (NPC) grafts up to 9 months in adult rats, with multiple examining time points to provide a unified working time frame for future transplantation study. Lots of Nestin+/Sox2+ human cells continuously migrate along the white matter tracts into distal brain parenchyma even long time after transplantation, providing a potential for curing diffuse brain damage. Further analysis reveals a significant heterogeneity of the long-term sustained neural stem cells (NSC)/NPCs that progressing throughout different stages, mimicking the neural development of human forebrain. More importantly, the initial GFAP expression in human grafts marks the NSC progression instead of terminal astrocyte differentiation. The distally migrating human cells continuously show the capability to produce new neurons, albeit at a low efficiency in the intact brain. Further investigations in neural disease models are needed. Such study would benefit neural cell therapy with regarding to the optimization of the transplantation strategy and choosing of acting mode by neural grafts (e.g. via cell replacement or ex vivo gene therapy).