Transplantation of mesenchymal stem cells reverses behavioural deficits and impaired neurogenesis caused by prenatal exposure to valproic acid

Abstract

Neurodevelopmental impairment can affect lifelong brain functions such as cognitive and social behaviour, and may contribute to aging-related changes of these functions. In the present study, we hypothesized that bone marrow-derived mesenchymal stem cells (MSC) administration may repair neurodevelopmental behavioural deficits by modulating adult hippocampal neurogenesis. Indeed, postnatal intracerebral transplantation of MSC has restored cognitive and social behaviour in mice prenatally exposed to valproic acid (VPA). MSC transplantation also restored post-developmental hippocampal neurogenesis, which was impaired in VPA-exposed mice displaying delayed differentiation and maturation of newly formed neurons in the granular cell layer of the dentate gyrus. Importantly, a statistically significant correlation was found between neuronal differentiation scores and behavioural scores, suggesting a mechanistic relation between the two. We thus conclude that post-developmental MSC administration can overcome prenatal neurodevelopmental deficits and restore cognitive and social behaviours via modulation of hippocampal adult neurogenesis.

Grafting Neural Stem and Progenitor Cells Into the Hippocampus of Juvenile, Irradiated Mice Normalizes Behavior Deficits

“…It was reported that grafted cells did not replace degenerated neuronal cells but provided trophic factors and/or suppressed the immune/inflammatory response that induces angiogenesis, neurogenesis, and/or neuroprotection ( 39 ). Grafted NSPCs or mesenchymal stem cells enhance proliferation of endogenous cells and neurogenesis in neurogenic regions including the hippocampus and SVZ ( 40 ). To elucidate the mechanism of the ameliorating effect of NSPC grafting after IR in the present study, we evaluated the trophic effect of the grafted NSPCs.…”

Stem cells transplantation in the treatment of patients with cerebral palsy

“…In diseases that affect the immune system and lead to mutations in the genome, the use of autologous SCs is not justified, due to the presence of the same disorders in themselves, so the effectiveness of their use will be low [37]. Another study found the inhibition of microglia formation and stimulation of neurogenesis in an experiment [42].…”

Stem cell therapy in autism: recent insights

“… 84 Mouse-derived MSCs were used in VPA-induced autism model, resulting in increasing neurogenesis and promoting maturation of newly formed neurons in the dentate gyrus 2 months after transplantation. 85 MSCs were expanded in culture for up to 20 passages and immunophenotyped for mesenchymal specific markers. Then thousands of MSCs in 5 µL MSC were transplanted into the right lateral ventricle.…”