Evaluation of a pectin-polymer and human recombinant prolactin in improving the viability and functionality of microencapsulated pancreatic islets

• Grant number: 21/12497-3
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: August 10, 2022
• End date: August 09, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Principal Investigator: Mari Cleide Sogayar
• Grantee: Isaura Beatriz Borges Silva
• Supervisor: Paulus de Vos
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: University of Groningen, Netherlands
• Associated to the scholarship: 19/21935-4 - Characterization of embryonic stem cell transcriptome during its differentiation into insulin-producing cells in the absence and presence of growth/differentiation peptide factors, BP.DR

Abstract

Islet cell transplantation represents a very promising therapeutic strategy for type 1 diabetes (T1D). However, upon transplantation, the host immune system initiates a response against the allograft, limiting the long-term efficacy of the transplant and demanding chronic immunosuppression. Microencapsulation emerged as an efficient technology to protect islet cells against the autoimmune and inflammatory response, and, consequently, avoid the side effects caused by immunosuppressors administration. However, insufficient biocompatibility of the microcapsule biopolymer mediates inflammatory responses, leading to progressive fibrotic overgrowth on the capsule surface and subsequent necrosis of the islets. Moreover, the suboptimal conditions encountered by islets upon isolation and transplantation promote damage-associated molecular patterns (DAMP)-induced immune activation after DAMPs interaction with pattern recognition receptors, especially Toll-Like Receptors (TLRs) 2/1. To improve biocompatibility and functionality of encapsulated islets, the Sogayar group developed a new biopolymeric composition by incorporating polylaminin to the Bioditrin biomaterial. Strategies to further improve the immunomodulatory capacities of microcapsules by grafting TLR2/1-inhibiting polymers, such as pectins, could reduce the host inflammatory responses and support long-term graft survival. Therefore, this project aims to undertake the physico-chemical characterization of polyLN-Bioditrin microcapsules, evaluate the role of DM (degree of methyl-esterification) 18-pectin in improving the anti-inflammatory and functionality of islets encapsulated with the polyLN-Bioditrin biopolymer and evaluate the beneficial effects of islet cell culture supplementation with human recombinant prolactin (rhPRL) prior to encapsulation. The results obtained with this project should allow better understanding of microcapsules biocompatibility, islet cell survival and functionality, in addition to providing improved immune-isolating devices for islet transplantation as a powerful approach to T1D treatment. (AU)