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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Figure 5

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Participation of cord blood–derived AT cells in neovascularization in vi...
Participation of cord blood–derived AT cells in neovascularization in vitro and in vivo. (a) The phase-contrast (left) and fluorescent (right) photomicrographs at the same microscopic field are shown. Green fluorescence-labeled AT cells contacted unlabeled HUVECs on matrix gel within 24 hours of coculture. (b) The labeled AT cells were incorporated into the EC network formed on the basement matrix gel within 3 days after coculture. (c–g) Frozen sections of tissues harvested from the ischemic hindlimb of nude rats 2 weeks after transplantation of fluorescence-labeled cord blood–derived AT cells. The labeled AT cells were sprouting from a place near the cell injection site indicated by * (c). AT cells further migrated into the interstitial regions among preserved skeletal myocytes (indicated by M). Numerous labeled AT cells were incorporated into and formed capillary-like networks (arrows in e and g), as well as tubular structures with a round lumen (arrowheads d–g). (f) Green fluorescence signals indicate localization of transplanted AT cells forming numerous capillary-like networks (arrows). (g) The phase-contrast photomicrograph of an adjacent section histochemically stained with alkaline phosphatase (AP) shows viable capillary ECs (dark blue colors) at identical locations of the incorporated AT cells seen in f. Bars, 50 μm.