An analysis of the induction mechanism of transdifferentiation of connective tissue-resident fibroblasts into endothelial cells of blood vessels

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[Introduction]Recently, bone marrow-derived endothelial progenitor cells and ES cells have been paid attention on as a source of vascular endothelial cells for regenerative therapy. However, the use of these cells has been pointed out to have immunological and ethical problems. In this study we examined whether connective tissue-resident fibroblasts are able to transdifferentiate into endothelial cells of blood vessels.[Materials and Methods]We carried out two experiments. In one experiment, a small piece of tissue graft was excised from corneal stroma of Tg mice of which endothelial cells of blood vessels expressed a lacZ gene, and was transplanted together with sarcoma cells into a cornea pocket of WT mice. In another experiment, corneal stroma cells (fibroblasts) from Tg mice were cultured, expanded and transfused into tail veins of WT mice whose cornea was engrafted with sarcoma beforehand to induce angiogenesis. After new blood vessels grew into the cornea, the cornea was processed for X-Gal staining. Here we used corneal stroma as a material, because a cornea contains no blood vessels and a corneal stroma consists of only stroma cells, fiblobrasts as cell components.[Result]In both experiments, a few lacZ positive cells were found in the endothelium of the newly formed blood vessel in the cornea.[Discussion]This result suggests that connective tissue-resident fibroblasts are a hopeful source of endothelial cells for regenerative therapy, gene therapy of blood vessel or for seeding on and lining the inner surface of vascular prosthetic grafts.