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Endothelial Progenitor Cell Therapy 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

Stroke is a major cause of death globally, which induces irreversible neuronal and endothelial cell death. Endothelial progenitor cell (EPC) based therapeutics result in neovascularization and the improvement of vascular perfusion, which benefits clinical stroke patients. Although EPC transplantation in experimental stroke models shows functional improvement, EPC therapy in clinical stroke patients continues to face an arduous task. In this chapter, we give a brief introduction of EPCs including the source of EPCs, methods of isolation and identification of EPC, the therapeutic potential for stroke, and signaling in modulating EPC function. Furthermore, we summarize the molecular mechanisms of EPCs action after transplantation either through differentiating into mature endothelial cells to replace damaged cells or by enhancing trophic/regenerative support for endogenous repair processes. We discuss the routes of transplantation and the modifying methods for EPCs safety and efficacy in vivo. Finally, we discuss the pros and cons for the application of EPCs for transplantation in clinical patients. Though EPC-based therapy is a potential treatment for stroke and holds promise for vascular regeneration, this field needs more study to uncover and resolve unsolved problems.

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Abbreviations

acLDL:

Acetylated low density lipoprotein

ACE2:

Angiotensin-converting enzyme 2

BBB:

Blood-brain barrier

BDNF:

Brain-derived neurotrophic factor

bFGF:

Basic fibroblast growth factor

BM:

Bone marrow

CACs:

Circulating angiogenic cells

CFU-Hil:

Colony forming unit-Hill

ECFC:

Endothelial colony forming cell

ECs:

Endothelial cells

EGF:

Epidermal growth factor

eNOS:

Endothelial NO synthase

EPCs:

Endothelial progenitor cells

EPO:

Erythropoietin

FACS:

Fluorescence activated cell

G-CSF:

Granulocyte colony-stimulating factor

GDNF:

Glial cell line-derived neurotrophic factor

GM-CSF:

Granulocyte-macrophage colony-stimulating factor

HGF:

Hepatocyte growth factor

HIF−Iα:

Hypoxia-inducible factor−1α

HMGB−1:

High-mobility group box 1

HSCs:

Hematopoietic stem cells

ICAM−1:

Intercellular adhesion molecule 1

IGF−1:

Insulin-like growth factor−1

IL−8:

Interleukin−8

MCP−1:

Monocyte chemoattractant protein−1

MMP−9:

Matrix metalloproteinase 9

MNCs:

Mononuclear cells

MRI:

Magnetic resonance imaging

NPCs:

Neural progenitor cells

PB:

Periblood blood

PDGF:

Platelet-derived growth factor

PlGF:

Placental growth factor

SDF−1α:

Stromal derived factor−1α

TGF-b2:

Transforming growth factor b2

tPA:

Recombinant tissue plasminogen activator

UCB:

Umbilical cord blood

UEA−E:

Ulex europaeus agglutinin 1

VEGF:

Vascular endothelial growth factor

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Author information

Authors and Affiliations

  1. Neuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Jiao Tong University, 1954 Hua Shan Road, 200030, Shanghai, China

    Yaning Li PhD, Yongting Wang PhD & Guo-Yuan Yang MD, PhD

  2. Department of Neurology, School of Medicine, Ruijin Hospital, Jiao Tong University, 200025, Shanghai, China

    Yuanyuan Ma MD & Guo-Yuan Yang MD, PhD

Authors
  1. Yaning Li PhD
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  2. Yuanyuan Ma MD
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  3. Yongting Wang PhD
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  4. Guo-Yuan Yang MD, PhD
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Corresponding author

Correspondence to Guo-Yuan Yang MD, PhD .

Editor information

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

Preclinical studies have shown great promise for EPC transplantation as a therapy for stroke. Beneficial effects from EPC transplantation have been observed, including functional improvement, increased neovascularization and decreased apoptotic cells. However, there are many fundamental unsolved problems, mentioned above, and relevant clinical trials are needed. A guideline called Stem Cell Therapy as an Emerging Paradigm for Stroke (STEPS) in 2009 (The STEPS Participants, 2009) has been drawn up. To some extent, this guideline can help scientists in all fields collaborate to accelerate the use of EPC transplantation in clinical patients for those who might benefit from EPC therapy. Currently, EPC transplantation for stroke treatment in clinic is only a vision, preclinical studies and clinical research are needed to maximize the therapeutic benefit and minimize the risks of EPCs transplantation in stroke.

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© 2015 Springer International Publishing Switzerland

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Li, Y., Ma, Y., Wang, Y., Yang, GY. (2015). Endothelial Progenitor Cell Therapy 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_7

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  • DOI: https://doi.org/10.1007/978-3-319-11481-1_7

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  • Online ISBN: 978-3-319-11481-1

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