9 Endothelial cells pre-treated with TGF��2 or BMP4 were seeded on polylactic acid scaffolds, implanted subcutaneously into nude mice and locally injected with differentiation medium. Upon explant, the scaffolds were sectioned and tissues stained positively for bone, cartilage or fat.9 The endothelial cells were labeled with fluorescent quantum dots prior to implantation, which confirmed the endothelial Dorsomorphin ALK origin of the bone, cartilage and fat tissues that formed in these scaffolds. Endothelial-derived stem cells have also been shown to differentiate into vascular smooth muscle cells in collagen scaffolds. Krenning et al.10 seeded endothelial progenitor cells (EPCs) on three-dimensional collagen sponges and induced them to undergo EndMT.
Immunofluorescence and electron microscopy revealed that the differentiated EPCs exhibited f-actin bundling, cytoplasmic stress fibers and cell-matrix interactions characteristic of the vascular smooth muscle phenotype.10 These findings suggest a promising use of endothelial-derived stem cells for both connective tissue and vascular tissue engineering. Using endothelial cells as a source of stem cells is advantageous in that they can be harvested using minimally invasive techniques. For example, a single biopsy punch could be used to harvest a small portion of a capillary bed from a patch of skin, from which a population of dermal microvascular endothelial cells could be isolated.33 This procedure would minimize the risk of complications associated with stem cell harvest from other tissue sources, such as bone marrow aspiration for isolation of bone marrow-derived stem cells.
Furthermore, not only are most tissues highly vascularized, but also it is well known that both hypoxia and vascular injury stimulate angiogenesis,34,35 which would ensure revascularization of the donor site. Another non-surgical option would be to isolate circulating endothelial progenitor cells (EPCs) from peripheral blood.36,37 These cells could be expanded in vitro and then stimulated to undergo EndMT. Transformed cells could be seeded onto scaffolds that are currently being used for tissue engineering (e.g., collagen-, polymer- or hydrogel-based scaffolds) and differentiated into the appropriate tissue type for surgical implantation (Fig. 1). Figure 1. Tissue engineering and regeneration using endothelial-derived stem cells.
Top panel: In the traditional in vitro tissue engineering approach, vascular endothelial Dacomitinib cells could be harvested and isolated from capillary beds from a patient … Another possible application of endothelial-derived stem cells is for the repair of injured tissues or treatment of degenerative diseases such as osteoarthritis, osteoporosis, muscular dystrophy, etc. Since most tissues are highly vascularized, they could potentially be regenerated directly in vivo by targeted injection of TGF-��2 or BMP4 to induce EndMT of local vascular endothelial cells.