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

Paul M George; Tonya M Bliss; Thuy Hua; Alex Lee; Byeongtaek Oh; Alexa Levinson; Swapnil Mehta; Guohua Sun; Gary K Steinberg

doi:10.1016/j.biomaterials.2017.07.020

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

Biomaterials. 2017 Oct:142:31-40. doi: 10.1016/j.biomaterials.2017.07.020. Epub 2017 Jul 12.

Authors

Paul M George¹, Tonya M Bliss², Thuy Hua², Alex Lee³, Byeongtaek Oh⁴, Alexa Levinson⁴, Swapnil Mehta⁵, Guohua Sun², Gary K Steinberg⁶

Affiliations

¹ Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA; Stanford Stroke Center and Stanford University School of Medicine, Stanford, CA, USA. Electronic address: pgeorge1@stanford.edu.
² Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA; Stanford Stroke Center and Stanford University School of Medicine, Stanford, CA, USA.
³ Department of Psychiatry, Stanford University School of Medicine, Stanford, CA, USA.
⁴ Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA.
⁵ Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
⁶ Department of Neurology, Stanford University School of Medicine, Stanford, CA, USA; Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA; Stanford Stroke Center and Stanford University School of Medicine, Stanford, CA, USA. Electronic address: gsteinberg@stanford.edu.

Abstract

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.

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

MeSH terms

Animals
Brain Infarction / pathology
Electric Conductivity*
Electric Stimulation
Gene Expression Regulation
Humans
Male
Neural Stem Cells / metabolism*
Neural Stem Cells / transplantation*
Polymers / chemistry*
Pyrroles / chemistry
RNA, Messenger / genetics
RNA, Messenger / metabolism
Rats, Nude
Recovery of Function*
Stroke / physiopathology*
Stroke / therapy*
Tissue Scaffolds / chemistry*
Vascular Endothelial Growth Factor A / metabolism

Substances

Polymers
Pyrroles
RNA, Messenger
Vascular Endothelial Growth Factor A
polypyrrole

Abstract

MeSH terms

Substances

Grants and funding