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This Article Full Text Full Text (PDF) All Versions of this Article: 71/6/2029    most recent biolreprod.104.031930v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Gerecht-Nir, S. Articles by Itskovitz-Eldor, J. Search for Related Content PubMed PubMed Citation Articles by Gerecht-Nir, S. Articles by Itskovitz-Eldor, J. Agricola Articles by Gerecht-Nir, S. Articles by Itskovitz-Eldor, J.

Vascular Development in Early Human Embryos and in Teratomas Derived from Human Embryonic Stem Cells¹

Biotechnology Interdisciplinary Unit and Rappaport Faculty of Medicine,³ Technion–Israel Institute of Technology, Haifa 31906, Israel Department of Obstetrics and Gynecology,⁴ Rambam Medical Center, Haifa 31906, Israel

During early human embryonic development, blood vessels are stimulated to grow, branch, and invade developing tissues and organs. Pluripotent human embryonic stem cells (hESCs) are endowed with the capacity to differentiate into cells of blood and lymphatic vessels. The present study aimed to follow vasculogenesis during the early stages of developing human vasculature and to examine whether human neovasculogenesis within teratomas generated in SCID mice from hESCs follows a similar course and can be used as a model for the development of human vasculature. Markers and gene profiling of smooth muscle cells and endothelial cells of blood and lymphatic vessels were used to follow neovasculogenesis and lymphangiogenesis in early developing human embryos (4–8 weeks) and in teratomas generated from hESCs. The involvement of vascular smooth muscle cells in the early stages of developing human embryonic blood vessels is demonstrated, as well as the remodeling kinetics of the developing human embryonic blood and lymphatic vasculature. In teratomas, human vascular cells were demonstrated to be associated with developing blood vessels. Processes of intensive remodeling of blood vessels during the early stages of human development are indicated by the upregulation of angiogenic factors and specific structural proteins. At the same time, evidence for lymphatic sprouting and moderate activation of lymphangiogenesis is demonstrated during these developmental stages. In the teratomas induced by hESCs, human angiogenesis and lymphangiogenesis are relatively insignificant. The main source of blood vessels developing within the teratomas is provided by the murine host. We conclude that the teratoma model has only limited value as a model to study human neovasculogenesis and that other in vitro methods for spontaneous and guided differentiation of hESCs may prove more useful.

¹ Supported in part by NIH contract grant 1RO1Hl73798-01.

² Correspondence: Joseph Itskovitz-Eldor, Department of Obstetrics and Gynecology, Rambam Medical Center, P.O. Box 9602, Haifa 31096, Israel. FAX: 972 4 854 2503; Itskovitz{at}rambam.health.gov.il