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Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation.

ABSTRACT: Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to nonspecific systemic immunosuppression results in immunodeficiency and has toxic effects on nonimmune cells. Here, we engineered hybrid spheroids of mesenchymal stem cells (MSCs) with rapamycin-releasing poly(lactic-co-glycolic acid) microparticles (RAP-MPs) to prevent immune rejection of islet xenografts in diabetic C57BL/6 mice. Hybrid spheroids were rapidly formed by incubating cell-particle mixture in methylcellulose solution while maintaining high cell viability. RAP-MPs were uniformly distributed in hybrid spheroids and sustainably released RAP for ~3 weeks. Locoregional transplantation of hybrid spheroids containing low doses of RAP-MPs (200- to 4000-ng RAP per recipient) significantly prolonged islet survival times and promoted the generation of regional regulatory T cells. Enhanced programmed death-ligand 1 expression by MSCs was found to be responsible for the immunomodulatory performance of hybrid spheroids. Our results suggest that these hybrid spheroids offer a promising platform for the efficient use of MSCs in the transplantation field.

SUBMITTER: Nguyen TT

PROVIDER: S-EPMC9401619 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation.

Nguyen Tiep Tien TT Pham Duc-Vinh DV Park Junhyeung J Phung Cao Dai CD Nepal Mahesh Raj MR Pandit Mahesh M Shrestha Manju M Son Youlim Y Joshi Mili M Jeong Tae Cheon TC Park Pil-Hoon PH Choi Dong-Young DY Chang Jae-Hoon JH Kim Ju-Hyun JH Kim Jae-Ryong JR Kim Il-Kug IK Yong Chul Soon CS Kim Jong Oh JO Sung Jong-Hyuk JH Jiang Hu-Lin HL Kim Hyung-Sik HS Yook Simmyung S Jeong Jee-Heon JH

Science advances 20220824 34

Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to nonspecific systemic immunosuppression results in immunodeficiency and has toxic effects on nonimmune cells. Here, we engineered hybrid spheroids of mesenchymal stem cells (MSCs) with rapamycin-releasing poly(lactic-<i>co</i>-glycolic acid) microparticles (RAP-MPs) to prevent immune rejection of islet xenografts in diabetic C57BL/6 mice. Hybrid spheroids were rapidly formed by incu ...[more]

PMID: 36001671

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Dataset Information

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation.

Publications

Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation.

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