Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice

Shoukang Zhu, Anuj Malhotra, Lisheng Zhang, Shanming Deng, Taifang Zhang, Neil J. Freedman, Robert Storms, Karsten Peppel, Pascal Goldschmidt-Clermont, Chunming Dong

Research output: Contribution to journalArticle

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Abstract

Aims: Vein graft endothelial damage is a key step in the development of neointimal hyperplasia, leading to vein graft failure. We sought to determine whether exogenous endothelial progenitor cells could promote vein graft re-endothelialization, and thereby ameliorate neointimal hyperplasia. Methods and results: Carotid artery interposition grafting was performed with syngeneic inferior vena cavae in mice with severe combined immunodeficiency (SCID). Lineage-negative human umbilical cord blood (hUCB) cells (or medium alone) were injected into vein-grafted mice intra-operatively and 2 weeks post-operatively. In vein grafts from hUCB cell-injected mice, we found human HLA-expressing endothelial cells, as well as increased levels of VEGF and FGF-2. Furthermore, hUCB cells secreted VEGF and FGF-2 in vitro. The markedly enhanced endothelial regeneration, likely resulting from both direct engraftment and paracrine actions of hUCB cells, inhibited inflammatory response, diminished intimal cell proliferation, and reduced neointimal hyperplasia in the vein grafts. Conclusions: hUCB cells may accelerate vein graft re-endothelialization via both direct differentiation into endothelial cells and release of paracrine factors to enhance endothelial regeneration and reduce inflammation. These data highlight a potential therapeutic role for cellular therapy in vessel injury.

Original languageEnglish
Pages (from-to)63-69
Number of pages7
JournalAtherosclerosis
Volume212
Issue number1
DOIs
StatePublished - Sep 1 2010

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Severe Combined Immunodeficiency
Fetal Blood
Hyperplasia
Veins
Blood Cells
Transplants
Fibroblast Growth Factor 2
Vascular Endothelial Growth Factor A
Regeneration
Endothelial Cells
Tunica Intima
Inferior Vena Cava
Endothelial Progenitor Cells
Carotid Arteries
Cell Proliferation
Inflammation
Wounds and Injuries
Therapeutics

Keywords

  • Endothelial progenitor cells
  • Umbilical cord blood
  • Vascular repair

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice. / Zhu, Shoukang; Malhotra, Anuj; Zhang, Lisheng; Deng, Shanming; Zhang, Taifang; Freedman, Neil J.; Storms, Robert; Peppel, Karsten; Goldschmidt-Clermont, Pascal; Dong, Chunming.

In: Atherosclerosis, Vol. 212, No. 1, 01.09.2010, p. 63-69.

Research output: Contribution to journalArticle

Zhu, S, Malhotra, A, Zhang, L, Deng, S, Zhang, T, Freedman, NJ, Storms, R, Peppel, K, Goldschmidt-Clermont, P & Dong, C 2010, 'Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice', Atherosclerosis, vol. 212, no. 1, pp. 63-69. https://doi.org/10.1016/j.atherosclerosis.2010.04.018
Zhu, Shoukang ; Malhotra, Anuj ; Zhang, Lisheng ; Deng, Shanming ; Zhang, Taifang ; Freedman, Neil J. ; Storms, Robert ; Peppel, Karsten ; Goldschmidt-Clermont, Pascal ; Dong, Chunming. / Human umbilical cord blood endothelial progenitor cells decrease vein graft neointimal hyperplasia in SCID mice. In: Atherosclerosis. 2010 ; Vol. 212, No. 1. pp. 63-69.
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