Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds
Aaron L. Carlson,
Neal K. Bennett,
Nicola L. Francis,
Apoorva Halikere,
Stephen Clarke,
Jennifer C. Moore,
Ronald P. Hart,
Kenneth Paradiso,
Marius Wernig,
Joachim Kohn,
Zhiping P. Pang () and
Prabhas V. Moghe ()
Additional contact information
Aaron L. Carlson: Rutgers University
Neal K. Bennett: Rutgers University
Nicola L. Francis: Rutgers University
Apoorva Halikere: Rutgers Robert Wood Johnson Medical School
Stephen Clarke: Rutgers University
Jennifer C. Moore: Human Genetics Institute of New Jersey
Ronald P. Hart: Rutgers University
Kenneth Paradiso: Rutgers University
Marius Wernig: Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine
Joachim Kohn: New Jersey Center for Biomaterials
Zhiping P. Pang: Rutgers Robert Wood Johnson Medical School
Prabhas V. Moghe: Rutgers University
Nature Communications, 2016, vol. 7, issue 1, 1-10
Abstract:
Abstract 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 ∼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 ∼38-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.
Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10862
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DOI: 10.1038/ncomms10862
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