Migration and differentiation of neural precursors derived from human embryonic stem cells in the rat brain

Abstract

Human embryonic stem (hES) cells provide a potentially unlimited cell source for regenerative medicine. Recently, differentiation strategies were developed to direct hES cells towards neural fates in vitro. However, the interaction of hES cell progeny with the adult brain environment remains unexplored. Here we report that hES cell-derived neural precursors differentiate into neurons, astrocytes and oligodendrocytes in the normal and lesioned brain of young adult rats and migrate extensively along white matter tracts. The differentiation and migration behavior of hES cell progeny was region specific. The hES cell-derived neural precursors integrated into the endogenous precursor pool in the subventricular zone, a site of persistent neurogenesis. Like adult neural stem cells, hES cell-derived precursors traveled along the rostral migratory stream to the olfactory bulb, where they contributed to neurogenesis. We found no evidence of cell fusion, suggesting that hES cell progeny are capable of responding appropriately to host cues in the subventricular zone.

Human-Induced Pluripotent Stem Cells form Functional Neurons and Improve Recovery After Grafting in Stroke-Damaged Brain

“…Tumor formation and graft overgrowth [45][46][47] from pluripotent stem cells and their derivatives are major hurdles for the application of stem cell therapy in stroke and other brain diseases. In previous studies, human iPSCs showed high tumorigenicity after intracerebral implantation in stroke-damaged brain [24].…”

ABC transporters, neural stem cells and neurogenesis – a different perspective

“…The anatomical location and lineage specificities of NSCs were only established when they were finally identified in the subependymal region and in the hippocampal dentate gyrus (DG), where they divide to generate progenitors that migrate along the rostral migratory stream to differentiate in the olfactory bulb or to integrate into the surrounding hippocampal neural circuitry, respectively [26][27][28]. Similar to HSCs, these nestin+ NSCs may be defined operationally as cells that can continuously self-renew and have the potential to generate intermediate and mature cells of both glial and neural lineages [29].…”

“…While their exact function and distribution is currently being assessed, they represent an interesting cell population, which may be used to study factors important for the differentiation and characterization of neurons, astrocytes and oligodendrocytes. Recently, there have been reports of NSC transplantations attempting to achieve functional recovery from CNS damage [171][172][173][174][175][176], and recent evidence suggests that NSCs may be a suitable source for the treatment of neurological diseases [22][23][24][25][26][27][177][178][179]. Due to their proliferative and differentiation capacity, NSCs will be important in fighting numerous brain disorders like AD, PD and Huntington's disease, as well as spinal cord disorders.…”

Bcl-XL modulates the differentiation of immortalized human neural stem cells

“…1,2,[23][24][25] Since neurodegenerative diseases are in many cases lateonset diseases, we found therefore of interest to study the in vivo properties of control or Bcl-X L overexpressing hNS1 cells after transplantation into the aged rat brain. Consistent with the in vitro data, we have also observed an increased neuron production and a diminished glia yield from Bcl-X L -overexpressing hNS1 cell transplants.…”