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Stem Cell-Paved Biobridge: A Merger of Exogenous and Endogenous Stem Cells Toward Regenerative Medicine in Stroke

  • Hung Nguyen
  • M. Grant Liska
  • Marci G. Crowley
  • Cesario V. Borlongan
Chapter
Part of the Springer Series in Translational Stroke Research book series (SSTSR)

Abstract

Stroke is a significant unmet clinical need with therapeutic options limited to tissue-type plasminogen activator (tPA), which has a small therapeutic window and risk for hemorrhagic transformation. Stroke is a multiphasic disease with a complex pathology. After the initial insult, a cascade of events occur causing secondary cell death and the expansion of the penumbra. The major contributing factors to this secondary cell death are depletion of growth factors, neuroinflammation, and disruption of the neurovascular unit. There is a need for more innovative and effective therapies that can target the diverse pathological consequences of stroke. To this end, stem cell therapy is a promising approach for stroke. Pre-clinical studies have demonstrated the potential of stem cells for treating neurological disorders, including stroke. Here, we discuss diverse stem cell types which have generated encouraging results for advancing to the clinic. Then, we examine the mechanisms of action of stem cells—cell replacement, by stander effect, and a novel biobridge concept advanced by our laboratory. These mechanisms work in concert to afford the neuroprotection and neuroregeneration after stroke. We envision that an in-depth understanding of the benefits and drawbacks of various stem cells and their mechanisms of action will guide the translational entry of stem cell therapy from the laboratory into the clinical setting.

Keywords

Adult-derived stem cells Ischemia pathology Stem cell mechanisms Stem cell migration Neuroregeneration Neuroprotection Extracellular matrix remodeling Stem cell therapies Translational research 

Abbreviations

BDNF

Brain-derived neurotrophic factor

BM-MSC

Bone marrow-derived mesenchymal stem cells

CCI

Controlled cortical impact

ECM

Extracellular matrix

EGF

Epithelial growth factor

FGF

Fibroblast growth factor

GDNF

Glial cell line-derived neurotrophic factor

hBMSCs

Human bone marrow stromal cells

IA

Intra-arterial

IC

Intracranial

IL-1β

Interleukin-1-beta

iPSCs

Induced pluripotent stem cells

IV

Intravenous

MCAO

Middle cerebral artery occlusion

MMP

Metallomatrix protein

NGF

Nerve growth factor

NSCs

Neural stem cells

SCF

Stem cell factor

SDF-1

Stromal-derived factor 1

SGZ

Subgranular zone

SVZ

Subventricular zone

TBI

Traumatic brain injury

TNF-α

Tumor necrosis-alpha

tPA

Tissue-type plasminogen activator

VEGF

Vascular endothelial growth factor

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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Hung Nguyen
    • 1
  • M. Grant Liska
    • 1
  • Marci G. Crowley
    • 1
  • Cesario V. Borlongan
    • 1
  1. 1.Center of Excellence for Aging and Brain Repair, Department of Neurosurgery and Brain RepairUniversity of South Florida Morsani College of MedicineTampaUSA

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