P-243 Poster of distinction

Bioprotect microcapsules and their therapeutical potential for type 1 diabetes mellitus

A.L. Campanha-Rodrigues, G. Grazioli, T.C. Oliveira, A.C.V. Campos-Lisbôa, T.R. Mares-Guia, M.C. Sogayar
NUCEL, University of São Paulo, Chemistry Institute, Biochemistry Department, Sao Paulo, Brazil

Background: Pancreatic islet microencapsulation represents an attractive therapeutical approach to Type 1 Diabetes Mellitus; however, maintenance of beta-cell function,which is strictly dependent upon islet architecture, remains a major problem. The loss of extracellular matrix (ECM) interactions, which occurs during islets isolation and purification, dramatically affects beta-cells survival and function.

Objective: Based on previous results from our group (Labriola, 2007) showing that laminin (LN), an important ECM component, improves islet functionality, we investigated whether BioProtect, a novel biomaterial composed of laminin (LN), chondroitin sulphate(CS) and alginate, would improve the islet microencapsulation/transplantation outcome when compared to Biodritin (CS-alginate only).

Methods: To assess the stability of BioProtect, microcapsules were evaluated for resistance to four different challenges(rotational, osmotic, temperature stress and culturing). Microcapsules were implanted i.p. in mice and retrieved after 7 and 30 days, for biocompatibility analysis. Gene expression was evaluated in rat pancreatic islets microencapsulated in BioProtect, by qRT-PCR, upon culturing for 48h. Apoptosis-related proteins were analyzed by WB. Diabetic mice were transplanted with BioProtect- or Biodritin-microencapsulated islets and monitored for weight, glycemia and OGTT.

Results: Both microcapsule formulations were stable and biocompatible. Reduction in pro-apoptotic (bax, bad, caspase 3) and an increase in anti-apoptotic (bcl-xL,bcl-2) transcripts, together with a decreased expression of stress-related genes (mcp1, hsp70), were evidenced. Protein analyses are underway. Mice transplanted with both microcapsule formulations achieved normoglycemia in a few days post-surgery, but those which received Bioprotect microencapsulated islets presented a better outcome, with 80% of total animals remaining euglycemic at 120 days, compared with only 27% for Biodritin. OGTTs showed that both types of microcapsules allowed a similar response to high glucose challenge, when compared to that observed for non-diabetic animals.

Conclusion: BioProtect constitutes a potential biomaterial for transplantation of microencapsulated islets.

P-243 Poster of distinction

Bioprotect microcapsules and their therapeutical potential for type 1 diabetes mellitus

A.L. Campanha-Rodrigues, G. Grazioli, T.C. Oliveira, A.C.V. Campos-Lisbôa, T.R. Mares-Guia, M.C. Sogayar
NUCEL, University of São Paulo, Chemistry Institute, Biochemistry Department, Sao Paulo, Brazil

Background: Pancreatic islet microencapsulation represents an attractive therapeutical approach to Type 1 Diabetes Mellitus; however, maintenance of beta-cell function,which is strictly dependent upon islet architecture, remains a major problem. The loss of extracellular matrix (ECM) interactions, which occurs during islets isolation and purification, dramatically affects beta-cells survival and function.

Objective: Based on previous results from our group (Labriola, 2007) showing that laminin (LN), an important ECM component, improves islet functionality, we investigated whether BioProtect, a novel biomaterial composed of laminin (LN), chondroitin sulphate(CS) and alginate, would improve the islet microencapsulation/transplantation outcome when compared to Biodritin (CS-alginate only).

Methods: To assess the stability of BioProtect, microcapsules were evaluated for resistance to four different challenges(rotational, osmotic, temperature stress and culturing). Microcapsules were implanted i.p. in mice and retrieved after 7 and 30 days, for biocompatibility analysis. Gene expression was evaluated in rat pancreatic islets microencapsulated in BioProtect, by qRT-PCR, upon culturing for 48h. Apoptosis-related proteins were analyzed by WB. Diabetic mice were transplanted with BioProtect- or Biodritin-microencapsulated islets and monitored for weight, glycemia and OGTT.

Results: Both microcapsule formulations were stable and biocompatible. Reduction in pro-apoptotic (bax, bad, caspase 3) and an increase in anti-apoptotic (bcl-xL,bcl-2) transcripts, together with a decreased expression of stress-related genes (mcp1, hsp70), were evidenced. Protein analyses are underway. Mice transplanted with both microcapsule formulations achieved normoglycemia in a few days post-surgery, but those which received Bioprotect microencapsulated islets presented a better outcome, with 80% of total animals remaining euglycemic at 120 days, compared with only 27% for Biodritin. OGTTs showed that both types of microcapsules allowed a similar response to high glucose challenge, when compared to that observed for non-diabetic animals.

Conclusion: BioProtect constitutes a potential biomaterial for transplantation of microencapsulated islets.