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 Blood, 15 December 2005, Vol. 106, No. 13, pp. 4184-4190.
Prepublished online as a Blood First Edition Paper on September 1, 2005; DOI 10.1182/blood-2005-01-0226.

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HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY

Presence of bone marrow–derived circulating progenitor endothelial cells in the newly formed lymphatic vessels

Piotr Religa, Renhai Cao, Meit Bjorndahl, Zhongjun Zhou, Zhenping Zhu, and Yihai Cao

From the Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institutet, Stockholm, Sweden; Department of Biochemistry, Faculty of Medicine, University of Hong Kong; and ImClone Systems, New York, NY.

Bone marrow (BM)-derived circulating endothelial precursor cells (CEPCs) have been reported to incorporate into newly formed blood vessels under physiologic and pathologic conditions. However, it is unknown if CEPCs contribute to lymphangiogenesis. Here we show that in a corneal lymphangiogenesis model of irradiated mice reconstituted with enhanced green fluorescent protein (EGFP)-positive donor bone marrow cells, CEPCs are present in the newly formed lymphatic vessels. Depletion of bone marrow cells by irradiation remarkably suppressed lymphangiogenesis in corneas implanted with fibroblast growth factor-2 (FGF-2). Further, transplantation of isolated EGFP-positive/vascular endothelial growth factor receptor-3-positive (EGFP+/VEGFR-3+) or EGFP+/VEGFR-2+ cell populations resulted in incorporation of EGFP+ cells into the newly formed lymphatic vessels. EGFP+/CEPCs were also present in peritumoral lymphatic vessels of a fibrosarcoma. These data suggest that BM-derived CEPCs may play a role in "lymphvasculogenesis."


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