Title |
Generation and transplantation of reprogrammed human neurons in the brain using 3D microtopographic scaffolds
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Published in |
Nature Communications, March 2016
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DOI | 10.1038/ncomms10862 |
Pubmed ID | |
Authors |
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, Prabhas V. Moghe |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 11 | 26% |
United Kingdom | 4 | 10% |
Canada | 2 | 5% |
France | 2 | 5% |
Spain | 2 | 5% |
Belgium | 1 | 2% |
India | 1 | 2% |
Australia | 1 | 2% |
Unknown | 18 | 43% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 29 | 69% |
Scientists | 7 | 17% |
Science communicators (journalists, bloggers, editors) | 3 | 7% |
Practitioners (doctors, other healthcare professionals) | 3 | 7% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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France | 1 | <1% |
Ireland | 1 | <1% |
Brazil | 1 | <1% |
Sweden | 1 | <1% |
United Kingdom | 1 | <1% |
United States | 1 | <1% |
Unknown | 254 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 66 | 25% |
Student > Master | 51 | 20% |
Researcher | 28 | 11% |
Student > Bachelor | 23 | 9% |
Professor > Associate Professor | 15 | 6% |
Other | 48 | 18% |
Unknown | 29 | 11% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 48 | 18% |
Engineering | 40 | 15% |
Biochemistry, Genetics and Molecular Biology | 38 | 15% |
Neuroscience | 33 | 13% |
Medicine and Dentistry | 20 | 8% |
Other | 38 | 15% |
Unknown | 43 | 17% |