Biochemistry Department - Chemistry Institute
Universidade de São Paulo
BioSafe: a novel biomaterial for pancreatic islets encapsulation and type 1 diabetes mellitus therapy
Camila Leal-Lopes1,2, Gisella Grazioli2, Thiago R Mares-Guia 2, Maria Lúcia C Corrêa-Giannella2,3, Mari C Sogayar1,2.
1Departamento de Bioquímica, Universidade de São Paulo, São Paulo, Brazil; 2NUCEL/NETCEM , Universidade de São Paulo, São Paulo, Brazil; 3Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
Pancreatic islets microencapsulation constitutes an attractive alternative therapy for type 1 diabetes, with the limiting factor being the disruption of extracellular matrix during the islet isolation procedure. Our objective was to investigate the potential of BioSafe (a novel biomaterial based on BioProtect® - alginate, chondroitin sulfate and laminin – replacing laminin with a polymerized polylaminin network), which may increase the functionality of microencapsulated cells. BioSafe microcapsules containing human pancreatic islets were tested for their ability to prevent macrophage activation: co-cultivation was carried for 9h followed by cytokines assessment by qRT-PCR. After encapsulation, rat pancreatic islets insulin secretion was evaluated in response to glucose (ELISA). Microcapsules biocompatibility was evaluated through peritoneal implantation in immunocompetent mice and morphological evaluation, 7 and 30 days after implantation. Gene expression related to cell function, stress and death were evaluated in microencapsulated rat pancreatic islets by qRT-PCR. Human pancreatic islets, encapsulated with BioProtect or BioSafe, induced similar expression levels of IL-1β (BioProtect: 0.059±0.04; BioSafe: 0.062±0,02) and TNF-α (0.046±0.02; 0.048±0.02) cytokines in macrophages. Similar insulin secretion was observed under low glucose in rat pancreatic islets encapsulated with both biomaterials (0.695±0.03; 0.068±0.03) and naked islets (1.51±0.01). Under high glucose stimulus, despite the higher levels of insulin secreted by naked islets (18.3±0,4), no significant difference occurred between islets encapsulated in the two biomaterials (BioProtect: 6.53±0,06; BioSafe: 6.27±0,1). At least 95% of the volume of microcapsules implanted was recovered and about 83% of the recovered capsules showed no pericapsular growth, being considered clean, with no significant differences between groups. The diameter of the capsules remained constant during the first seven days of the trial (0.95±0.0005; 0.94±0.004), but there was a significant increase in diameter after 30 days of implantation for both biomaterials (1.18±0.047; 117±007). We observed increased expression of anti-apoptotic genes, Bcl-xl (1.23±0,71), Bcl-2 (495±85), and of the function-related gene, insulin 1 (1,02±0,34), in islets encapsulated with BioSafe relative to BioProtect. Decreased expression of pro-apoptotic genes and stress-related genes was also observed: caspase 3 (0,769±0,15), Bax (0,858±0,083), Hsp-70 (0,673±0,24), Mcp-1 (0,797±0,18). In conclusion, BioSafe is a superior biomaterial for pancreatic islets encapsulation, being able to: maintain the encapsulated islets functionality, protect against programmed cell death and provide a less stressful environment. However, further investigations are required to assess their potential for long-term transplantation.
FAPESP. CNPq. CAPES. BNDES. FINEP. MS-DECIT.
11:00 - 12:30
|Cellular Encapsulation||BioSafe: a novel biomaterial for pancreatic islets encapsulation and type 1 diabetes mellitus therapy||Room 111-112|
15:30 - 17:00
|Islet Cell Transplantation - Miscellaneous||Embryonic stem cell differentiation into insulin-producing cells (IPCS): functional characterization of the Purkinje Cell Protein 4 (PCP4) gene in this process||Room 111-112|