한빛사 논문
Tiep Tien Nguyen1,2, Duc-Vinh Pham1, Junhyeung Park1, Cao Dai Phung1, Mahesh Raj Nepal1, Mahesh Pandit1, Manju Shrestha1, Youlim Son3, Mili Joshi3, Tae Cheon Jeong1, Pil-Hoon Park1, Dong-Young Choi1, Jae-Hoon Chang1, Ju-Hyun Kim1, Jae-Ryong Kim3, Il-Kug Kim3, Chul Soon Yong1, Jong Oh Kim1, Jong-Hyuk Sung4,5, Hu-Lin Jiang6,7,8,9, Hyung-Sik Kim10,11, Simmyung Yook2*, Jee-Heon Jeong1,12*
1College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, Republic of Korea. 2College of Pharmacy, Keimyung University, Daegu, 42601, Republic of Korea. 3College of Medicine, Yeungnam University, Daegu, 42415, Republic of Korea. 4College of Pharmacy, Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, 21983, Republic of Korea. 5Epibiotech Co. Ltd., Incheon, 21983, Republic of Korea. 6State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. 7Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, China Pharmaceutical University, Nanjing, 210009, China. 8Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing, 210009, China. 9NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, China Pharmaceutical University, Nanjing, 210009, China. 10Department of Life Science in Dentistry, School of Dentistry, Pusan National University, Yangsan, 50612, Republic of Korea. 11Dental and Life Science Institute, Pusan National University, Yangsan, 50612, Republic of Korea. 12Department of Precision Medicine, School of Medicine, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
*Corresponding author
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.
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