Potentiated Local Immunomodulatory Effect of Uniformly Engineered Hybrid Stem Cell/Drug Depot Spheroids on Xeno-Source Pancreatic Islet Transplantation Outcomes
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Here, we report a method to potentiate immunomodulatory effect of mesenchymal stem cells (MSCs) by constructing hybrid spheroids with rapamycin-releasing PLGA microspheres (RAP-MS). These hybrids were devised to prevent the strong rejection of xeno-source pancreatic islets. RAP-MS exhibited a narrow size of 4.4 ± 1.7 µm. RAP was sustainably released for 30 days without burst event. Here, the hybrids were rapidly formed in the methylcellulose medium. The hybrids achieved a large size while maintaining high cell viability. Interestingly, RAP-MS were uniformly distributed throughout the hybrids. Importantly, RAP-MS potentiated the effects of MSCs by upregulating pivotal gene expression, thereby improving MSC retention. As the result, these hybrids effectively enhanced islet xenograft survival time after their co-localization under kidney capsule of diabetic mice. We envision that these hybrid spheroids would provide a promising platform for efficient use of MSCs for immunomodulation.