Creating a graft-friendly environment for stem cells in diseased brains

Organ preservation versus regeneration: the good, the bad, and the ugly Most of the adult CNS lacks the ability to regenerate in a physiologically meaningful manner, even though adult neurogenesis [...]
Most of the adult CNS lacks regenerative activity in terms of both neuron birth and neurite outgrowth. While this regeneration-unfriendly environment of the adult CNS may preserve the existing neuronal circuitry that takes years to develop in higher organisms, it also poses a major obstacle for CNS repair later in life. In this issue of theJCI, Song et al. report on their development of a strategy that uses region-specific and molecularly engineered astrocytes to turn an unfavorable brain environment into a favorable one for engrafted neural stem/progenitor cells (NSC/NPCs). In a rat model of Parkinson's disease (PD), cografting NPCs with midbrainderived astrocytes engineered to overexpress the transcription factors Nurrl and Foxa2 promotes maturation and survival of the graft, resulting in therapeutic improvement. The results of this study raise the prospect of using modified astrocytes to improve the survival, maturation, and integration of engrafted NSC/NPCs as a restorative treatment for PD.