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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-06-1877.
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Blood, 1 April 2003, Vol. 101, No. 7, pp. 2675-2678
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Brief report
Effective contribution of transplanted vascular progenitor cells
derived from embryonic stem cells to adult neovascularization in proper
differentiation stage
Takami Yurugi-Kobayashi,
Hiroshi Itoh,
Jun Yamashita,
Kenichi Yamahara,
Hideyo Hirai,
Takuya Kobayashi,
Minetaro Ogawa,
Satomi Nishikawa,
Shin-Ichi Nishikawa, and
Kazuwa Nakao
From the Department of Medicine and Clinical Science,
Department of Molecular Genetics, Kyoto University Graduate
School of Medicine, Department of Microbiology, Kyoto Prefectural
University of Medicine, Department of Pharmacology, Kyoto University
Graduate School of Medicine, Kyoto, Japan; and Department
of Cell Differentiation, Institute of Molecular Embryology and
Genetics, Kumamoto University, Kumamoto, Japan.
We demonstrated that Flk-1+ cells derived from
mouse embryonic stem (ES) cells can differentiate into both endothelial
cells (ECs) and mural cells (MCs) to suffice as vascular progenitor cells (VPCs). In the present study, we investigated the importance of
the stage of ES cell differentiation on effective participation in
adult neovascularization. We obtained Flk-1+
LacZ-expressing undifferentiated VPCs. Additional culture of these VPCs
with vascular endothelial growth factor (VEGF) resulted in a mixture of
ECs and MCs (differentiated VPCs). We injected VPCs subcutaneously into
tumor-bearing mice. Five days after the injection, whereas
undifferentiated VPCs were often detected as nonvascular cells,
differentiated VPCs were more specifically incorporated into developing
vasculature mainly as ECs. VPC-derived MCs were also detected in
vascular walls. Furthermore, transplantation of differentiated VPCs
augmented tumor blood flow in nude mice. These results indicate that a
specific vascular contribution in adult neovascularization can be
achieved by selective transplantation of ES cell-derived VPCs in
appropriate differentiation stages, which should be the basis for
vascular regeneration schemes.
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