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Prepublished online as a Blood First Edition Paper on December 12, 2002; DOI 10.1182/blood-2002-06-1877.
Submitted June 26, 2002
Accepted November 22, 2002
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
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Kyoto, Japan
Department of Molecular Genetics, Kyoto University Graduate School of Medicine, Kyoto, Japan
Department of Microbiology, Kyoto Prefectural University of Medicine, Kyoto, Japan
Department of Pharmacology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Department of Cell Differentiation, Kumamoto University, Institute of Molecular Embryology and Genetics, Kumamoto, Japan
* Corresponding author; email: hiito{at}kuhp.kyoto-u.ac.jp.
We demonstrated that Flk-1+ cells derived from mouse embryonic stem (ES) cells can differentiate into both endothelial cells (EC) and mural cells (MC) to suffice as "vascular progenitor cells (VPC)". In the present study, we investigated the importance of ES cell differentiation stage on effective participation in adult neovascularization.
We obtained Flk-1+ LacZ-expressing undifferentiated VPC. Additional culture of these VPC with VEGF resulted in a mixture of EC and MC (differentiated VPC). We injected VPC subcutaneously into tumor-bearing mice. Five days after the injection, whereas undifferentiated VPC were often detected as non-vascular cells, differentiated VPC were more specifically incorporated into developing vasculature mainly as EC. VPC-derived MC were also detected in vascular walls. Furthermore, transplantation of differentiated VPC augmented tumor blood flow in nude mice. These results indicate that specific vascular contribution in adult neovascularization can be achieved by selective transplantation of ES cell-derived VPC in appropriate differentiation stages, which should be the basis for vascular regeneration schemes.
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