SUNGKYUNKWAN UNIVERSITY SCHOOL OF MEDICINE
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Research Highlights
Engineering of hybrid spheroids of mesenchymal stem cells and drug depots for immunomodulating effect in islet xenotransplantation
Tiep Tien Nguyen, Duc-Vinh Pham, Junhyeung Park, Cao Dai Phung, Mahesh Raj Nepal, Mahesh Pandit, Manju Shrestha, Youlim Son, Mili Joshi, Tae Cheon Jeong, Pil-Hoon Park, Dong-Young Choi, Jae-Hoon Chang, Ju-Hyun Kim, Jae-Ryong Kim, Il-Kug Kim, Chul Soon Yong, Jong Oh Kim, Jong-Hyuk Sung, Hu-Lin Jiang, Hyung-Sik Kim, Simmyung Yook, Jee-Heon Jeong
SCIENCE ADVANCES
Immunomodulation is an essential consideration for cell replacement procedures. Unfortunately, lifelong exposure to non-specific systemic immunosuppression results in immunodeficiency and has toxic effects on non-immune cells.
In this study, we report an effective methodology to potentiate the immunomodulatory properties of MSCs via engineering hybrid spheroids with rapamycin (RAP)-releasing poly(lactic-co-glycolic acid) (PLGA) microparticle depots (RAP-MPs). The devised hybrid spheroids were locoregionally transplanted with rat pancreatic islets into diabetic C57BL/6 mice to prevent the strong immune rejection of these xeno-sourced islets. This approach only required a single treatment with a low-dose immunosuppressant but resulted in long-term effects on immunosuppression.
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 (200-4000 ng RAP/recipient) significantly prolonged islet survival times and promoted the generation of regional regulatory T cells. Enhanced Programmed Death-Ligand 1 (PD-L1) 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. This study was published in Science Advances in August 2022 (Nguyen et al., Sci. Adv. 8, eabn8614 (2022)).
In this study, we report an effective methodology to potentiate the immunomodulatory properties of MSCs via engineering hybrid spheroids with rapamycin (RAP)-releasing poly(lactic-co-glycolic acid) (PLGA) microparticle depots (RAP-MPs). The devised hybrid spheroids were locoregionally transplanted with rat pancreatic islets into diabetic C57BL/6 mice to prevent the strong immune rejection of these xeno-sourced islets. This approach only required a single treatment with a low-dose immunosuppressant but resulted in long-term effects on immunosuppression.
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 (200-4000 ng RAP/recipient) significantly prolonged islet survival times and promoted the generation of regional regulatory T cells. Enhanced Programmed Death-Ligand 1 (PD-L1) 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. This study was published in Science Advances in August 2022 (Nguyen et al., Sci. Adv. 8, eabn8614 (2022)).