(A) General strategy for creating endothelialized tissue fragments in vitro.
(B) The endothelialization technique is adaptable to all tissue types examined in this study, including islets, brain fragments, heart fragments, intestine fragments, kidney fragments, liver fragments, lung fragments, and even spheroids of induced pluripotent stem cells. Scale bars, 1,000 μm.
(C) Gross observation of a mini-sized vascularized islet (upper) and an islet alone (lower). Scale bars, 500 μm.
(D) Formation of a three-dimensional mini-sized vascularized mouse islet in co-cultures of islets with HUVECs and human MSCs. The arrowheads indicate the blood vessel-like structures. Scale bars, 250 μm.
(E) Immunofluorescence staining of the pre-transplantation vascularized islet (upper) and islet alone (lower). GCG, glucagon; hCD31, human CD31; INS, insulin; SST, somatostatin. Scale bars, 100 μm.
(F) Hierarchical clustering of the pancreatic lineage 121 genes with the relevance in pancreatic development or β cell function. Each row in the heatmap represents a sample, and each column represents the expression level of a gene. The color scale below the heatmap represents the raw Z score ranging from green (high expression) to red (low expression).