Endothelium Trans Differentiated from Wharton's Jelly Mesenchymal Cells Promote Tissue Regeneration: Potential Role of Soluble Pro-Angiogenic Factors

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.

Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta

“…Tie-2 expression was raised to various degrees in BMSCs, AMSCs, and PMSCs during endothelial differentiation, but with a falloff in UMSCs. To better define the expression of endothelial-related proteins and the unique functions of cells after endothelial differentiation, an immunostaining assay [20, 21] and an acLDL-uptaking assay [22] were performed respectively (Fig. 1b).…”

“…Aguilera et al . [20] demonstrated that Wharton’s jelly-derived mesenchymal cells expressed high levels of endothelial markers (CD31 and KDR) and also synthesized NO after 30 days of endothelial differentiation. Additionally, Ikhapoh et al [35] and Benavides et al [21] respectively reported that BMSC and amniotic fluid-derived stem cells were capable of differentiation into endothelial cells.…”

Wharton's jelly derived mesenchymal stromal cells: Biological properties, induction of neuronal phenotype and current applications in neurodegeneration research

“…In this respect, WJMSC may represent a much better choice, as they are much easily attainable, exhibit excellent proliferative and differentiation potential, pose no ethical concern, and are of invariant, consistent, young age. However, only recently has interest emerged towards WJMSCs and their promising therapeutic potential (Aguilera et al, 2014;Batsali et al, 2013;Hsieh et al, 2013).…”

Upregulation of endothelial gene markers in Wharton's jelly mesenchymal stem cells cultured on polyelectrolyte multilayers

“…Confluent MSCs are sensitive to VEGF differentiation mediated by KDR activation. A slight variation of KDR for WJ‐ and BM‐MSCs on both coatings is probably due to the absence of VEGF in EBM‐2 ® . Related to mRNA regulation, the corresponding protein synthesis, by WJ‐ and BM‐MSCs, was evaluated by Western blot.…”