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We recently demonstrated that intra-pancreatic (iPan) delivery of conditioned media (CM) generated by human bone marrow-derived multipotent stromal cells (hBM-MSC) can act as a biotherapeutic to reduce hyperglycemia in STZ-treated mice by stimulating endogenous islet regeneration. We have established analogous stromal cell lines derived from human islet cultures that grow adherent to plastic and possess multipotent mesodermal differentiation in vitro. Furthermore, CM generated by these human pancreas-derived MSC (hPanc-MSC) contained proangiogenic stimuli within extracellular vesicles (EVs) that accelerated blood vessel regeneration after injection into ischemic hindlimbs. Herein, we investigated whether iPan-injection of CM generated by hPanc-MSC could stimulate islet regeneration in STZ-treated mice. We hypothesized that islet regenerative stimuli would be harboured within EVs secreted by …