4.8 Article

Electrical preconditioning of stem cells with a conductive polymer scaffold enhances stroke recovery

Journal

BIOMATERIALS
Volume 142, Issue -, Pages 31-40

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2017.07.020

Keywords

Conductive polymer; Stroke recovery; Neural stem cell; Electrical stimulation; Tissue engineering; Cell transplantation

Funding

  1. American Brain Foundation/Academy of Neurology
  2. NIH [K08NS089976, RO1 N2058784]
  3. California Institute of Regenerative Medicine [RB5-07363]
  4. Bernard and Ronni Lacroute
  5. William Randolph Hearst Foundation

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Exogenous human neural progenitor cells (hNPCs) are promising stroke therapeutics, but optimal delivery conditions and exact recovery mechanisms remain elusive. To further elucidate repair processes and improve stroke outcomes, we developed an electrically conductive, polymer scaffold for hNPC delivery. Electrical stimulation of hNPCs alters their transcriptome including changes to the VEGF-A pathway and genes involved in cell survival, inflammatory response, and synaptic remodeling. In our experiments, exogenous hNPCs were electrically stimulated (electrically preconditioned) via the scaffold 1 day prior to implantation. After in vitro stimulation, hNPCs on the scaffold are transplanted intracranially in a distal middle cerebral artery occlusion rat model. Electrically preconditioned hNPCs improved functional outcomes compared to unstimulated hNPCs or hNPCs where VEGF-A was blocked during in vitro electrical preconditioning. The ability to manipulate hNPCs via a conductive scaffold creates a new approach to optimize stem cell-based therapy and determine which factors (such as VEGF-A) are essential for stroke recovery. (C) 2017 Elsevier Ltd. All rights reserved.

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