Engraftment of enteric neural progenitor cells into the injured adult brain

BMC Neuroscience

Research Article

Naema Nayyar¹  Jorg Dietrich¹  Ryo Hotta²  Nandor Nagy²  Lily Cheng²  Aaron Zuckerman²  Allan M. Goldstein³  Michael Whalen⁴  Jaime Belkind-Gerson⁵ 

[1] Department of Neurology, Division of Neuro-Oncology, and Center for Regenerative Medicine, Massachusetts General Hospital, Harvard Medical School, 02114, Boston, MA, USA;Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 02114, Boston, MA, USA;Department of Pediatric Surgery, Massachusetts General Hospital, Harvard Medical School, 02114, Boston, MA, USA;Pediatric Neurogastroenterology Program, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge St #575, 02114, Boston, MA, USA;Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 02114, Boston, MA, USA;Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, 02114, Boston, MA, USA;Pediatric Neurogastroenterology Program, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge St #575, 02114, Boston, MA, USA;

关键词: Enteric neuronal progenitor cells;    Stem cells;    Brain injury;    Cell transplantation;    Brain repair;   

DOI  :  10.1186/s12868-016-0238-y

 received in 2015-10-25, accepted in 2016-01-03,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundA major area of unmet need is the development of strategies to restore neuronal network systems and to recover brain function in patients with neurological disease. The use of cell-based therapies remains an attractive approach, but its application has been challenging due to the lack of suitable cell sources, ethical concerns, and immune-mediated tissue rejection. We propose an innovative approach that utilizes gut-derived neural tissue for cell-based therapies following focal or diffuse central nervous system injury.ResultsEnteric neuronal stem and progenitor cells, able to differentiate into neuronal and glial lineages, were isolated from the postnatal enteric nervous system and propagated in vitro. Gut-derived neural progenitors, genetically engineered to express fluorescent proteins, were transplanted into the injured brain of adult mice. Using different models of brain injury in combination with either local or systemic cell delivery, we show that transplanted enteric neuronal progenitor cells survive, proliferate, and differentiate into neuronal and glial lineages in vivo. Moreover, transplanted cells migrate extensively along neuronal pathways and appear to modulate the local microenvironment to stimulate endogenous neurogenesis.ConclusionsOur findings suggest that enteric nervous system derived cells represent a potential source for tissue regeneration in the central nervous system. Further studies are needed to validate these findings and to explore whether autologous gut-derived cell transplantation into the injured brain can result in functional neurologic recovery.

【 授权许可】

CC BY   
© Belkind-Gerson et al. 2016