Abstract
BackgroundMesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo.MethodsMesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO).ResultshWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures.ConclusionThese results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors.
Highlights
Mesenchymal cells (MSCs) are a heterogeneous group of adult stem cells able to proliferate and differentiate into osteocytes, chondrocytes or adipocytes [1,2], as well as into non mesodermal precursors, from which they can be trans-differentiated towards hepatocytes [3], neurons [4] or endothelial cells [5,6]
Using flow cytometry, we observed that hWMSCs were positive for vimentin (95%), but showed a low expression of the endothelial markers CD31 and KDR
3) These cells can be trans-differentiated into endothelial cells, which in turn show expression of endothelial markers, such as CD31, KDR and Endothelial nitric oxide synthase (eNOS), and importantly, they produce nitric oxide (NO). 4) In vivo experiments showed that hWMSCs trans-differentiated into endothelial cells have greater regenerative capacity than nondifferentiated hWMSC. 5) Conditioned medium derived from hWMSC-End, enhanced the percentage of wound healing and vascularization in the scar, suggesting that these cells may release pro-angiogenic factors
Summary
Mesenchymal cells (MSCs) are a heterogeneous group of adult stem cells able to proliferate and differentiate into osteocytes, chondrocytes or adipocytes [1,2], as well as into non mesodermal precursors, from which they can be trans-differentiated towards hepatocytes [3], neurons [4] or endothelial cells [5,6]. Mesenchymal stem cells isolated from Wharton’s jelly (hWMSCs) have high telomerase activity [17], high proliferative capacity [17] and long- term culturing of expanded [18,19,20]. These cells cannot undergo tumor transformation [20,21,22,23] and have a low expression of histocompatibility complex class I molecules [18,19,22], while they do not express major histocompatibility complex class II [18,22,24]. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton’s jelly (hWMSCs) can accelerate tissue repair in vivo
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