期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms10862
关键词
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资金
- NIH RESBIO: Integrated Resource for Polymeric Biomaterials [P41 EB001046]
- NSF IGERT on Stem Cell Science and Engineering
- DGE [0801620]
- Exploratory Research Grant from NJSCR and Stem Cell Core Grant from NJCST
- NJSCR Fellowship on Translational Regenerative Medicine [NIH T32 EB005583, NIH 5R00NS051401]
- NIH NIAAA [F31AA024033]
- NIAAA [R01 AA023797]
- NIH NIDA [DA035594, DA03968]
Cell replacement therapy with human pluripotent stem cell-derived neurons has the potential to ameliorate neurodegenerative dysfunction and central nervous system injuries, but reprogrammed neurons are dissociated and spatially disorganized during transplantation, rendering poor cell survival, functionality and engraftment in vivo. Here, we present the design of three-dimensional (3D) microtopographic scaffolds, using tunable electrospun microfibrous polymeric substrates that promote in situ stem cell neuronal reprogramming, neural network establishment and support neuronal engraftment into the brain. Scaffold-supported, reprogrammed neuronal networks were successfully grafted into organotypic hippocampal brain slices, showing an similar to 3.5-fold improvement in neurite outgrowth and increased action potential firing relative to injected isolated cells. Transplantation of scaffold-supported neuronal networks into mouse brain striatum improved survival similar to B38-fold at the injection site relative to injected isolated cells, and allowed delivery of multiple neuronal subtypes. Thus, 3D microscale biomaterials represent a promising platform for the transplantation of therapeutic human neurons with broad neuro-regenerative relevance.
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