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Transplantation of Adipose-Derived Stem Cells in Stroke

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Cellular Therapy for Stroke and CNS Injuries

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

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Abstract

Not only is stroke second only to cardiac ischemia as a leading cause of death worldwide, but it also drastically impaired the quality of life of the survivors through its crippling neurological sequelae which account for the third leading cause of disability. Instead of merely a loss of functioning neurons from ischemia, stroke triggers a cascade of adverse events including inflammation, oxidative stress, and apoptosis that perpetuates the initial ischemic damage. Current therapeutic strategies, including the use of thrombolytic agents and other non-pharmaceutical approaches, have their limitations either because of the risk of complications or focusing only on the prevention of brain damage and rehabilitation. More importantly, none has been convincingly shown to improve neurological outcome in patients with stroke once the brain tissue is infarcted. Accumulating evidence has indicated that, instead of being only neuroprotective, stem cells actually possess neurorestorative function for promoting recovery of the injured brain tissue. Accordingly, cell transplant therapy with adipose-derived mesenchymal stem cells (ADSC) has recently emerged as a potentially feasible therapeutic option not only because of their abundance and relative ease of being harvested, but also because of the possibility of autologous implantation and their demonstrated multiple beneficial biological actions against stroke in experimental settings, namely paracrine effects, transdifferentiation, and immunomodulation, that could enhance brain plasticity such as neurogenesis, remyelination, synaptogenesis, and angiogenesis in the recovery process. The nature and source of ADSC as well as their demonstrated therapeutic potential against stroke, the clinical perspective in stroke treatment, and the potential risks are reviewed.

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Abbreviations

ADSC:

Adipose-derived mesenchymal stem cells

APC:

Antigen-presenting cell

BDNF:

Brain-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

BMP2:

Bone morphogenetic protein 2

CSPG:

Chondroitin sulphate proteoglycans

CXCR4:

Chemokine receptor type 4

DCX:

Doublecortin

FACS:

Fluorescence-activated cell sorting

FGF2:

Fibroblast growth factor 2

G-CSF:

granulocyte colony-stimulating factor

GDNF:

Glial derived neurotrophic factor

GFAP:

Glial fibrillary acidic protein

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HGF:

Hepatocyte growth factor

IDO:

Indoleamine-2,3-dioxygenase

IGF-1:

Insulin-like growth factor-1

IL:

Interleukin

IL-1R:

Interleukin 1 receptor

iPSC:

Induced pluripotent stem cells

MACS:

Magnetic activated cell sorting

MAP2:

Microtubule-associated protein 2

MCAO:

Middle cerebral artery occlusion

MHC-II:

Major histocompatibility complex class II

NeuN:

Neuronal nuclei

NF:

Neurofilament

NGF:

Nerve growth factor

NT-3:

Neurotrophin-3

Olig-2:

Oligodendrocyte

PAI-1:

Plasminogen activator inhibitor-1

ROS:

Reactive oxygen species

rtPA:

Recombinant tissue plasminogen activator

SDF-1:

Stromal cell-derived factor 1

SVF:

Stromal vascular fraction

SYP:

Synaptophysin

TGF-β1:

Transforming growth factor beta 1

TLR-4:

Toll-like receptor-4

TNF-alpha:

Tumor necrosis factor-alpha

VCAM-1:

Vascular cell adhesion molecule 1

VEGF:

Vascular endothelial growth factor

vWF:

Von Willebran factor

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Conflict of Interest

The author declares no conflict of interests. No part of the manuscript has been previously published in any language and all illustrations are original.

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Authors and Affiliations

  1. Department of Emergency Medicine, E-Da Hospital, I-Shou University, No. 1, Yi-Da Road, Jiao-Su Village, Yan-Chao District, 824, Kaohsiung City, Taiwan, Republic of China

    Cheuk-Kwan Sun M.D., Ph.D.

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  1. Cheuk-Kwan Sun M.D., Ph.D.
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Correspondence to Cheuk-Kwan Sun M.D., Ph.D. .

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Editors and Affiliations

  1. Department of Neurosurgery, SUNY Upstate Medical College, Syracuse, New York, USA

    Li-Ru Zhao

  2. Loma Linda University School of Medicine Depts of Physiology, Loma Linda, California, USA

    John H. Zhang

Conclusions

Conclusions

Taken into consideration the possibility of autologous transplantation without significant reduction in therapeutic potency with the donor’s age, the absence of serious ethical issues and concerns regarding disease transmission from allogeneic sources, the abundance, the relative ease of acquisition and culturing, the superior immunomodulatory function compared with stem cells from other sources, as well as the promising therapeutic efficacy in the treatment of stroke in the experimental settings, it is conceivable that ADSC will have an important role to play in the clinical setting of stroke treatment. Results from large-scaled, randomized, and well-controlled clinical trials are eagerly awaited to turn the possibility into reality.

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Sun, CK. (2015). Transplantation of Adipose-Derived Stem Cells in Stroke. In: Zhao, LR., Zhang, J. (eds) Cellular Therapy for Stroke and CNS Injuries. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-11481-1_9

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  • DOI: https://doi.org/10.1007/978-3-319-11481-1_9

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