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From Neurogenic Niche to Site of Injury: Stem Cell-Mediated Biobridge for Brain Repair

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Biology in Stem Cell Niche

Part of the book series: Stem Cell Biology and Regenerative Medicine ((STEMCELL))

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Abstract

Cell replacement and “bystander” effects of stem cells are currently the widely postulated mechanisms of stem cell-mediated repair. In a recent study, we reported efficacy of modified mesenchymal stromal cell (MSC) transplantation in animal models of traumatic brain injury (TBI), revealing data that corroborate the therapeutic potential of stem cell transplantation for brain injuries, and importantly, evidence that support another mechanism of action of transplanted stem cells. We found that intracerebrally administered SB623 cells (gene-modified human MSCs provided by SanBio Inc.) improved TBI-induced neurobehavioral deficits, via a unique mechanism of action involving the formation of a “biobridge” during the repair phase of TBI. Using immunohistochemistry and laser capture assay, we observed localization of this biobridge in an area between the neurogenic subventricular zone and the injured cortex. This stem cell-paved biobridge expressed high levels of extracellular matrix metalloproteinases (MMPs), which initially co-existed with a stream of transplanted MSCs, and later contained a few to non-detectable grafts and overgrown by newly recruited host cells. We advanced the concept that the biobridge facilitated the long-distance migration of host cells from the neurogenic niche to the injured brain site, representing a key regenerative process that highlights the potential of stem cell grafts to initiate endogenous repair mechanisms. Further studies on elucidating graft-host interaction will likely contribute to in-depth characterization of stem cell-paved biobridge, as a robust brain repair mechanism alongside cell replacement and trophic factor secretion, into a new treatment strategy for TBI and other neurological dysfunctions. In this chapter, we discuss the characteristics of stem cell paved-biobridges, the novel mechanism by which they promote neural repair in a rat model of TBI, and describe the clinical significance, challenges and opportunities of employing this novel stem cell-mediated brain repair concept for the treatment of other neurological disorders beyond TBI.

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Abbreviations

CC:

Corpus callosum

DCX:

Doublecortin

ECM:

Extracellular matrix

MSC:

Mesenchymal stromal cell

MMP:

Matrix metalloproteinase

OEC:

Olfactory ensheathing cell

PD:

Parkinson’s disease

SC:

Schwann cell

SGZ:

Subgranular zone

SVZ:

Subventricular zone

TBI:

Traumatic brain injury

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Acknowledgments

This work was supported by SanBio Inc. (CVB).

Competing Interests

CVB is an inventor on a patent application related to the stem cell research reported here. CVB received research financial support from SanBio Inc. for this study. CVB is additionally supported by NIH NINDS R01NS071956-01, NIH NINDS R21 NS089851-01, and DOD W81XWH-11-1-0634.

Author information

Authors and Affiliations

  1. Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, 12901 Bruce B. Downs Blvd, Tampa, FL, 33612, USA

    Ike De La Pena, Naoki Tajiri, Sandra Acosta, Stephanny Reyes, Arum Yoo, Michael McGrogan & Cesar V. Borlongan

  2. Sanbio Inc., Mountain View, CA, 94041, USA

    Irina Aizman, Ernest Yankee & Damien Bates

Authors
  1. Ike De La Pena
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  2. Naoki Tajiri
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  3. Sandra Acosta
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  4. Stephanny Reyes
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  5. Arum Yoo
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  6. Michael McGrogan
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  7. Irina Aizman
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  8. Ernest Yankee
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  9. Damien Bates
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  10. Cesar V. Borlongan
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Corresponding author

Correspondence to Cesar V. Borlongan .

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Editors and Affiliations

  1. Sprott Centre for Stem Cell Research, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

    Kursad Turksen

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De La Pena, I. et al. (2015). From Neurogenic Niche to Site of Injury: Stem Cell-Mediated Biobridge for Brain Repair. In: Turksen, K. (eds) Biology in Stem Cell Niche. Stem Cell Biology and Regenerative Medicine. Springer, Cham. https://doi.org/10.1007/978-3-319-21702-4_7

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