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Neovascularization and tissue regeneration by endothelial progenitor cells in ischemic stroke

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Abstract

Endothelial progenitor cells (EPCs) are immature endothelial cells (ECs) capable of proliferating and differentiating into mature ECs. These progenitor cells migrate from bone marrow (BM) after vascular injury to ischemic areas, where they participate in the repair of injured endothelium and new blood vessel formation. EPCs also secrete a series of protective cytokines and growth factors that support cell survival and tissue regeneration. Thus, EPCs provide novel and promising potential therapies to treat vascular disease, including ischemic stroke. However, EPCs are tightly regulated during the process of vascular repair and regeneration by numerous endogenous cytokines that are associated closely with the therapeutic efficacy of the progenitor cells. The regenerative capacity of EPCs also is affected by a range of exogenous factors and drugs as well as vascular risk factors. Understanding the functional properties of EPCs and the factors related to their regenerative capacity will facilitate better use of these progenitor cells in treating vascular disease. Here, we review the current knowledge of EPCs in cerebral neovascularization and tissue regeneration after cerebral ischemia and the factors associated with their regenerative function to better understand the underlying mechanisms and provide more effective strategies for the use of EPCs in treating ischemic stroke.

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Abbreviations

EPCs:

Endothelial progenitor cells

BM:

Bone marrow

ECs:

Endothelial cells

rtPA:

Recombinant tissue plasminogen activator

SDF-1:

Stromal cell-derived factor-1

VEGF:

Vascular endothelial growth factor

VEGFR-2:

Vascular endothelial growth factor receptor-2

IGF-1:

Insulin-like growth factor-1

MMP-9:

Matrix metalloproteinase-9

G-CSF:

Granulocyte colony stimulating factor

VCAM-1:

Vascular cell adhesion molecule-1

HIF-1:

Hypoxia-inducible factor-1

PSGL-1:

P selectin glycoprotein ligand-1

ICAM-1:

Intercellular adhesion molecule-1

MCAO:

Middle cerebral artery occlusion

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Funding

This study was supported by Technology Research of the Education Department of Jilin Province, China (grant no. JJkH20170063kJ), to Yan Ma, and Technology Research of the Education Department of Jilin Province, China (grant no. JJKH20190653KJ), to Da-Wei Li.

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Li, J., Ma, Y., Miao, XH. et al. Neovascularization and tissue regeneration by endothelial progenitor cells in ischemic stroke. Neurol Sci 42, 3585–3593 (2021). https://doi.org/10.1007/s10072-021-05428-3

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