Abstract
Several studies have demonstrated the multipotentiality of human neonatal foreskin stromal cells (hNSSCs) as being able to differentiate into adipocytes and osteoblasts and potentially other cell types. Recently, we demonstrated that hNSSCs play a role during in vitro angiogenesis and appear to possess a capacity to differentiate into endothelial-like cells; however, their angiogenic potential within an ex vivo environment remains unclear. Current study shows hNSSCs to display significant migration potential in the undifferentiated state and high responsiveness in the in vitro wound healing scratch assay. When hNSSCs were seeded onto the top of the CAM, human von Willebrand factor (hVWF), CD31, smooth muscle actin (SMA), and factor XIIIa positive cells were observed in the chick endothelium. CAMs transplanted with endothelial-differentiated hNSSCs displayed a higher number of blood vessels containing hNSSCs compared to CAMs transplanted with undifferentiated hNSSCs. Interestingly, undifferentiated hNSSCs showed a propensity to differentiate towards ectoderm with indication of epidermal formation with cells positive for CD1a, CK5/6, CK19, FXIIIa, and S-100 cells, which warrant further investigation. Our findings imply a potential angiogenic role for hNSSCs ex vivo in the differentiated and undifferentiated state, with potential contribution to blood vessel formation and potential application in tissue regeneration and vascularization.
Highlights
Angiogenesis is a multifaceted process that involves endothelial cell proliferation, migration and differentiation, extracellular matrix (ECM) remodelling, and the functional development of new blood vessels from preexisting vasculature
We have previously shown the ability of human neonatal foreskin stromal cells (hNSSCs) to differentiate into endothelial-like cells in vitro [8]; the ability of hNSSCs to participate in neovasculature ex vivo has not been addressed to date
The current study suggests the potential of hNSSCs to differentiate along the endothelial lineage following placement ex vivo in an angiogenic niche, namely, the chorioallantoic membrane (CAM)
Summary
Angiogenesis is a multifaceted process that involves endothelial cell proliferation, migration and differentiation, extracellular matrix (ECM) remodelling, and the functional development of new blood vessels from preexisting vasculature. Stem cell transplantation has emerged in the last few years as a potential therapy for several diseases, given the potential of stem cells to differentiate into multiple lineages and the prospect that they may offer trophic support for cell survival, tissue restoration, and functional improvement [1,2,3]. HNSSCs were shown to express thirtythree CD markers including known stromal cell-associated as well as several novel markers [6]. These cells could be induced to differentiate into cells expressing endothelial markers and to form densely packed large diameter tubules during in vitro angiogenesis assay [5, 8]. The angiogenic capacity of hNSSCs ex vivo remains unclear
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