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

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

doi:10.1016/j.biomaterials.2017.07.020

Cited by 89 publications

(92 citation statements)

References 45 publications

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“…Recently, Soma and his team developed an injectable biological substrate that self-assembles within the host tissues from a laminin-derived epitope, thereby mimicking the brain's major extracellular protein, supporting long-term survival and functional maturation of NSCs [67]. Remarkably, scaffolds assembled with conductive polymers were shown to allow electrical stimulation of NSCs before transplantation, with enhanced functional recovery [68]. This strategy is based on a combination of the scaffolding technology with preconditioning treatment.…”

Section: Use Of Scaffolds In Nsc Transplantationmentioning

confidence: 99%

Preconditioning and Cellular Engineering to Increase the Survival of Transplanted Neural Stem Cells for Motor Neuron Disease Therapy

et al. 2018

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Despite the extensive research effort that has been made in the field, motor neuron diseases, namely, amyotrophic lateral sclerosis and spinal muscular atrophies, still represent an overwhelming cause of morbidity and mortality worldwide. Exogenous neural stem cell-based transplantation approaches have been investigated as multifaceted strategies to both protect and repair upper and lower motor neurons from degeneration and inflammation. Transplanted neural stem cells (NSCs) exert their beneficial effects not only through the replacement of damaged cells but also via bystander immunomodulatory and neurotrophic actions. Notwithstanding these promising findings, the clinical translatability of such techniques is jeopardized by the limited engraftment success and survival of transplanted cells within the hostile disease microenvironment. To overcome this obstacle, different methods to enhance graft survival, stability, and therapeutic potential have been developed, including environmental stress preconditioning, biopolymers scaffolds, and genetic engineering. In this review, we discuss current engineering techniques aimed at the exploitation of the migratory, proliferative, and secretive capacity of NSCs and their relevance for the therapeutic arsenal against motor neuron disorders and other neurological disorders.

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Section: Use Of Scaffolds In Nsc Transplantationmentioning

confidence: 99%

Preconditioning and Cellular Engineering to Increase the Survival of Transplanted Neural Stem Cells for Motor Neuron Disease Therapy

et al. 2018

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“…Experimentation using electrical properties may be beneficial to differentiate stem cells and re-build neural circuitry. The use of conductive scaffolds makes plausible the manipulation of stem cells, in particular, the use of Polypyrrole (PPy) (George et al, 2017). Following the seeding of cells, ion channel density and neurite outgrowth are manipulated by signaling intrinsic electrical cues.…”

Section: Polypyrrolementioning

confidence: 99%

“…By applying electrical stimulation to NSCs seeded on laminin-coated PPy films in a timely manner demonstrates neuron differentiation (Stewart et al, 2015). A study preconditioning human neural progenitor cells in a cell chamber system seeded on a PPy scaffold presents an improvement in neurologic function in a rat stroke model (George et al, 2017). The VEGF-A pathway gene expression was altered following electrical stimulation, correlated with endogenous vasculature remodeling (George et al, 2017).…”

Section: Polypyrrolementioning

confidence: 99%

“…A study preconditioning human neural progenitor cells in a cell chamber system seeded on a PPy scaffold presents an improvement in neurologic function in a rat stroke model (George et al, 2017). The VEGF-A pathway gene expression was altered following electrical stimulation, correlated with endogenous vasculature remodeling (George et al, 2017). This suggests that electrically preconditioning stem cells can be beneficial to enhance stroke recovery.…”

Section: Polypyrrolementioning

confidence: 99%

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Stroke Repair via Biomimicry of the Subventricular Zone

Matta

Gonzalez

2018

Front. Mater.

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Stroke is among the leading causes of death and disability worldwide, 85% of which are ischemic. Current stroke therapies are limited by a narrow effective therapeutic time and fail to effectively complete the recovery of the damaged area. Magnetic resonance imaging of the subventricular zone (SVZ) following infarct/stroke has allowed visualization of new axonal connections and projections being formed, while new immature neurons migrate from the SVZ to the peri-infarct area. Such studies suggest that the SVZ is a primary source of regenerative cells for the repair and regeneration of stroke-damaged neurons and tissue. Therefore, the development of tissue engineered scaffolds that serve as a bioreplicative SVZ niche would support the survival of multiple cell types that reside in the SVZ. Essential to replication of the human SVZ microenvironment is the establishment of microvasculature that regulates both the healthy and stroke-injured blood-brain barrier, which is dysregulated poststroke. In order to reproduce this niche, understanding how cells interact in this environment is critical, in particular neural stem cells, endothelial cells, pericytes, ependymal cells, and microglia. Remodeling and repair of the matrix-rich SVZ niche by endogenous reparative mechanisms may then support functional recovery when enhanced by an artificial niche that supports the survival and proliferation of migrating vascular and neuronal cells. Critical considerations to mimic this area include an understanding of resident cell types, delivery method, and the use of biocompatible materials. Controlling stem cell survival, differentiation, and migration are key factors to consider when transplanting stem cells. Here, we discuss the role of the SVZ architecture and resident cells in the promotion and enhancement of endogenous repair mechanisms. We elucidate the interplay between the extracellular matrix composition and cell interactions prior to and following stroke. Finally, we review current cell and neuronal niche biomimetic materials that allow for a tissue-engineered approach in order to promote structural and functional restoration of neural circuitry. By creating an artificial mimetic SVZ, tissue engineers can strive to facilitate tissue regeneration and functional recovery.

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“…Graphene has shown promise in vitro but the in vivo biocompatibility and tolerance remains unknown. Implantation of electrically preconditioned cells was recently demonstrated using a conductive polymer scaffold where Human neural progenitor cells (hNPCs) cultured on a polypyrrole scaffold and exposed to electrical stimulation upregulated genes in the VEGF-A pathway (George et al, 2017). When cells on these scaffolds were stimulated and transplanted onto the cortical surface of stroke-injured rats they elicited functional improvement in multiple behavioral tasks and increased the peri-infarct vasculature in a VEGF-dependent manner compared to unconditioned cells; however, no surviving cells were detected at two weeks posttransplantation.…”

Section: Biomaterials In Novel Treatmentsmentioning

confidence: 99%