Human vessels were long-lasting as they were stabilized by humanMSC-derived perivascular cells (Fig. 3e–g)13,14. Interestingly, the humaniPSC-LB transplant vascular networkswere similar in density and morphologyto those of adult livers, whereas the vasculature in only HUVECsand human MSC transplants were much less dense; functional vesselswere of similar diameter (approximately 12 mm) in both settings (in iPSCLBtransplants, and in HUVEC and human MSC transplants) (Fig. 3h, i,and Supplementary Figs 11 and 12). Animal studies suggest that endothelialcells not onlyform passive conduits to deliver nutrients and oxygen butalso establish an instructive vascular niche, which stimulates liver organogenesisand regeneration through elaboration of paracrine trophogens.Our transplantation approach provided a unique intravital monitoringsystem for evaluating human iPSC-derived organ maturation and differentiationthroughout the organogenesis, enabling us to dissect thepreviously uncharacterized roles of stromal cell types in human organdevelopment
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