한빛사논문
Tiep Tien Nguyena,1, Tung Thanh Phama,1, Hanh Thuy Nguyena, Mahesh Raj Nepala, Cao Dai Phunga, Zhiwei Youa, Nikita Katilaa, Nirmala Tillija Puna, Tae Cheon Jeonga, Dong-Young Choia, Pil-Hoon Parka, Chul Soon Yonga, Jong Oh Kima, Simmyung Yookb,*, Jee-Heon Jeonga,*
a College of Pharmacy, Yeungnam University, Gyeongsan, Gyeongbuk, 38541, South Korea
b College of Pharmacy, Keimyung University, Daegu, 42601, South Korea
1These authors equally contributed to this work.
*Corresponding author : Simmyung Yook, Jee-Heon Jeong
Abstract
Host immune response remains an obstacle in cell-replacement therapy for treating type I diabetes. Long-term systemic immunosuppression results in suboptimal efficacy and adverse reactions. Thus, “cell-particle hybrids” of pancreatic islets and tissue-adhesive, polydopamine-coated, FK506-loaded biodegradable microspheres (PD-FK506-MS) were developed to locally modulate the immune response at the transplantation site. Coating of FK506-MS with PD enabled the rapid formation of stable cell-particle hybrids without significant changes in islet viability and functionality. Extremely low quantities of FK506 (approximately 600 ng per recipient) sustainably released from cell-particle hybrids effectively prolonged survival of xenogeneic islet graft. Interestingly, FK506 exhibited extended bioavailability in the grafts but was undetectable in systemic circulation and other tissues. Moreover, mRNA expression of inflammatory cytokines was significantly inhibited in the PD-FK506-MS-containing grafts but not in lymphoid organs. This study presents a promising platform that facilitates the translation of local immunomodulation towards an effective strategy with improved safety profiles for treating type I diabetes.
Keywords : Tissue adhesion; Local immunomodulation; Diabetes; Polydopamine coating
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