Engineering “cell-particle hybrids” of pancreatic islets and bioadhesive FK506-loaded polymeric microspheres for local immunomodulation in xenogeneic islet transplantation
Tiep Tien Nguyen, Tung Thanh Pham, Hanh Thuy Nguyen, Mahesh Raj Nepal, Cao Dai Phung, Zhiwei You, Nikita Katila, Nirmala Tillija Pun, Tae Cheon Jeong, Dong-Young Choi, Pil-Hoon Park, Chul Soon Yong, Jong Oh Kim, Simmyung Yook,*, Jee-Heon Jeong,*
Clinical pancreatic islet transplantation is now considered one of the safest and least invasive transplant procedures for treating type I diabetes. However, the need for intensive immunosuppression to prolong graft survival remains a great challenge due to the adverse effects of systemic immunosuppressive drugs.
Synchronous delivery of immunomodulatory agents with pancreatic islets using synthetic materials, including polymeric scaffolds and hydrogels, has been developed to establish a translatable strategy with improved efficacy and safety profiles. Nevertheless, the use of these platforms may increase the transplant mass, limit transplantation sites, and interfere with nutrient and biological waste diffusion.
In this study, we report a novel method of engineering “cell-particle hybrids” of pancreatic islets and tissue-adhesive, polydopamine-coated, FK506-loaded biodegradable microspheres (PDFK506-MS) were developed to locally modulate the immune response at the transplantation site. Coating FK506-MS with PD enabled the rapid formation of stable cell-particle hybrids without significant islet viability and functionality changes. Extremely low quantities of FK506 (~600 ng per recipient) sustainably released from cell-particle hybrids effectively prolonged the 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 was published in Biomaterials in August 2019 (Biomaterials, Vol. 221, Nov 2019, 11945).