Fibroblasts resident in the tissue transform into vascular endothelial cells of newly-formed blood vessels
Abstract: The mechanism of angiogenesis and the origin of vascular endothelial cells (VECs) of newly-formed blood vessels (NBVs) remain to be elucidated. Here we present a new mechanism of angiogenesis and a new source of VECs. We cultured dermal fibroblasts from a rabbit, labeled them with various markers, and autologously injected them into the rabbit ear chamber. Labeled VECs were observed in NBVs in the chamber. Then we cultured corneal stromal cells (CSCs) from Flk1-lacZ mice and Tie2-GFP mice. CSCs from Flk1-lacZ mice were transplanted via a tail vein into wild type (WT) mice in which angiogenesis had previously been induced in the cornea. lacZ positive VECs were found in the NBVs of the corneas of recipient mice. Corneal stromal tissue grafts from Tie2-GFP mice were transplanted into the corneas of WT mice where afterward angiogenesis was induced. GFP fluorescence was observed in the NBVs in the mice which received tissue grafts from Tg mice. These results suggest that fibroblasts can transform into VECs. We propose a new mechanism of angiogenesis, in which blood vessels may elongate by incorporation of tissue-resident fibroblasts into the endothelia and usefulness of fibroblasts as a source of VECs for a gene and cell therapy for vascular diseases.
Key words: Angiogenesis, Vascular endothelial cell, Fibroblast