Islet transplantation has been demonstrated to be a promising therapy for type 1 diabetes mellitus. Although it is a minimally invasive operating procedure and provides easy access for graft monitoring, subcutaneous transplantation of the islet only has limited therapeutic outcomes, owing to the poor capacity of skin tissue to foster revascularization in a short period. Herein, 3D cell spheroids of clinically accessible umbilical cord blood mesenchymal stem cells and human umbilical vein endothelial cells are formed and employed for codelivery with β cells subcutaneously. The 3D stem cell spheroids, which can secrete multiple proangiogenic and prosurvival growth factors, induce robust angiogenesis and prevent β cell graft death, as indicated by the results of in vivo bioluminescent tracking and histological analysis. These experimental data highlight the efficacy of the 3D stem cell spheroids that are fabricated using translationally applicable cell types in promoting the survival and function of subcutaneously transplanted β cells.

In article number 1900254, Chieh‐Cheng Huang, and co‐workers demonstrate the use of 3D stem cell spheroids assembled from mesenchymal stem cells and vascular endothelial cells as a therapeutic agent for promoting the survival and function of subcutaneously engrafted cells. By differentiating into perivascular cells or secreting multiple paracrine factors, the 3D stem cell spheroids exert potent pro‐angiogenic and pro‐survival effects.