Transplanted cord blood–derived endothelial precursor cells augment postnatal neovascularization
Toyoaki Murohara, … , Kazuo Matsui, Tsutomu Imaizumi
Toyoaki Murohara, … , Kazuo Matsui, Tsutomu Imaizumi
Published June 1, 2000
Citation Information: J Clin Invest. 2000;105(11):1527-1536. https://doi.org/10.1172/JCI8296.
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Transplanted cord blood–derived endothelial precursor cells augment postnatal neovascularization

Abstract

Endothelial precursor cells (EPCs) have been identified in adult peripheral blood. We examined whether EPCs could be isolated from umbilical cord blood, a rich source for hematopoietic progenitors, and whether in vivo transplantation of EPCs could modulate postnatal neovascularization. Numerous cell clusters, spindle-shaped and attaching (AT) cells, and cord-like structures developed from culture of cord blood mononuclear cells (MNCs). Fluorescence-trace experiments revealed that cell clusters, AT cells, and cord-like structures predominantly were derived from CD34-positive MNCs (MNCCD34+). AT cells and cell clusters could be generated more efficiently from cord blood MNCs than from adult peripheral blood MNCs. AT cells incorporated acetylated-LDL, released nitric oxide, and expressed KDR, VE-cadherin, CD31, and von Willebrand factor but not CD45. Locally transplanted AT cells survived and participated in capillary networks in the ischemic tissues of immunodeficient nude rats in vivo. AT cells thus had multiple endothelial phenotypes and were defined as a major population of EPCs. Furthermore, laser Doppler and immunohistochemical analyses revealed that EPC transplantation quantitatively augmented neovascularization and blood flow in the ischemic hindlimb. In conclusion, umbilical cord blood is a valuable source of EPCs, and transplantation of cord blood–derived EPCs represents a promising strategy for modulating postnatal neovascularization.

Authors

Toyoaki Murohara, Hisao Ikeda, Junli Duan, Satoshi Shintani, Ken-ichiro Sasaki, Hiroyuki Eguchi, Ichiro Onitsuka, Kazuo Matsui, Tsutomu Imaizumi

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AT cells had EC-like functions and expressed cell surface markers in vit...
AT cells had EC-like functions and expressed cell surface markers in vitro. At day 7 of culture (a) AT cells took up DiI-ac-LDL. (b) AT cells were positive for endothelial constitutive NO synthase (ecNOS) immunostaining. (c and d) Incubating AT cells with DAF-2 DA, a NO-specific fluorescence indicator, showed that hVEGF165 (50 ng/mL) (d), but not saline (c), induced NO release from AT cells. Bars, 50 μm in c and d. (e) Flow cytometric analyses of AT cells at day 7 of culture (n = 8). Horizontal bars indicate positive antigen gates as determined by an isotype-matched IgG control study. AT cells were positive for KDR (52 ± 5%), VE-cadherin (62 ± 2%), CD34 (62 ± 7%), and CD31 (57 ± 9%), but not for CD45 (7 ± 3%). Data are percentage of positive cells.