Adult Human Brain Neural Progenitor Cells (NPCs) and Fibroblast-Like Cells Have Similar Properties In Vitro but Only NPCs Differentiate into Neurons

Abstract

The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC) culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP) of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia), and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs). These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5–6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting AhNPC-based experiments.

Perivascular Mesenchymal Stem Cells From the Adult Human Brain Harbor No Instrinsic Neuroectodermal but High Mesodermal Differentiation Potential

“…Two recent reports provided the first hints of the existence of pericytes in the human adult brain [13,14]; however, the groups reported different observations. Although Paul et al reported no coexpression of NSCs and pericyte markers by aBPMCs but rather an intrinsic neuroectodermal differentiation potential [14], Park et al reported coexpression of these markers but no neuroectodermal differentiation potential [13].…”

“…Recently, such perivascular MSCs, or "fibroblast-like cells," were also described in the adult human brain [13,14]. Both reports described fibroblast-like cells deriving from the perivascular niche as harboring long-term expandability and mesodermal differentiation potential [13,14].…”

“…Recently, such perivascular MSCs, or "fibroblast-like cells," were also described in the adult human brain [13,14]. Both reports described fibroblast-like cells deriving from the perivascular niche as harboring long-term expandability and mesodermal differentiation potential [13,14]. Paul et al noted no coexpression of neuroprecursor markers during expansion but neuronal differentiation potential of these MSCs [14], whereas Park et al reported coexpression of neuroprecursor markers but a lack of neuronal differentiation potential [13].…”

“…Both reports described fibroblast-like cells deriving from the perivascular niche as harboring long-term expandability and mesodermal differentiation potential [13,14]. Paul et al noted no coexpression of neuroprecursor markers during expansion but neuronal differentiation potential of these MSCs [14], whereas Park et al reported coexpression of neuroprecursor markers but a lack of neuronal differentiation potential [13]. Karow et al recently reported the induction of fully mature neurons from human pericytes by overexpression of SOX2 and MASH1 [15,16], supporting the interest in these cells for regenerative approaches to various neurological diseases.…”

In Vitro Differentiation of Human Neural Progenitor Cells Into Striatal GABAergic Neurons

“…Limited self-renewal capacity and the tendency toward acquisition of karyotypic aberrations are regarded as potential limitations of nonimmortalized NPCs for basic science and translational medicine studies [67,68]. In the present study, we used NPCs that had been immortalized by transduction with v-MYC [34].…”