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. BorlonganEmail author
Part of the Springer Series in Translational Stroke Research book series (SSTSR)


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.


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



Brain-derived neurotrophic factor


Bone marrow-derived mesenchymal stem cells


Controlled cortical impact


Extracellular matrix


Epithelial growth factor


Fibroblast growth factor


Glial cell line-derived neurotrophic factor


Human bone marrow stromal cells








Induced pluripotent stem cells




Middle cerebral artery occlusion


Metallomatrix protein


Nerve growth factor


Neural stem cells


Stem cell factor


Stromal-derived factor 1


Subgranular zone


Subventricular zone


Traumatic brain injury


Tumor necrosis-alpha


Tissue-type plasminogen activator


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
    Email author
  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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