title: Therapeutic potential of laminin-biodritin microcapsules for type 1 diabetes mellitus.
abstract: Pancreatic islet microencapsulation constitutes an attractive therapy for type 1 diabetes mellitus; however, long-term β-cell function remains a major problem. Loss of extracellular matrix interactions during islet isolation dramatically affects β-cell viability. We have previously shown beneficial effects of laminin (LN) in human islet cultures. Herein, we investigated whether LN could improve the outcome of transplantation after islet microencapsulation in Biodritin, an alginate-based material. To test LN-Biodritin stability, microcapsules were subjected to different types of in vitro stress. Focusing on biocompatibility, empty microcapsules were coincubated with the RAW 264.7 macrophage cell line for up to 24 h, and empty beads were implanted IP in mice and retrieved for analyses after 7 and 30 days. Upon culturing for 48 h, mRNA, protein levels, and caspase 3 activity were evaluated in islets microencapsulated with LN-Biodritin. Mice rendered diabetic by streptozotocin injection were transplanted with microencapsulated islets, followed by assessment of body weight, glycemia, and graft function (evaluated by OGTT). Graft efficiency was observed upon microencapsulated islet explantation. The results obtained showed that LN-Biodritin microcapsules were as stable and biocompatible as Biodritin. Modulation of mRNA and protein levels suggested protection against apoptosis and islet stress. Mice transplanted with LN-Biodritin microencapsulated islets presented a better outcome at 198 days postsurgery. Graft explantation led animals to hyperglycemia. In conclusion, LN-Biodritin constitutes a very promising biomaterial for islet transplantation.
authors.affiliation: Chemistry Institute, Biochemistry Department, Cell and Molecular Therapy Center (NUCEL/NETCEM), School of Medicine, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Ana Lucia
authors.initials: AL
authors.lastname: Campanha-Rodrigues
authors.forename: Gisella
authors.initials: G
authors.lastname: Grazioli
authors.forename: Talita C
authors.initials: TC
authors.lastname: Oliveira
authors.forename: Ana Carolina V
authors.initials: AC
authors.lastname: Campos-Lisbôa
authors.forename: Thiago R
authors.initials: TR
authors.lastname: Mares-Guia
authors.forename: Mari C
authors.initials: MC
authors.lastname: Sogayar
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D002214:Capsules / Q000737:chemistry*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002809:Chondroitin Sulfates / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000628:therapy*; D007316:Insemination, Artificial, Heterologous; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D007797:Laminin / Q000737:chemistry*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000464:Alginates; D001672:Biocompatible Materials; C529638:Biodritin; D002214:Capsules; D007328:Insulin; D053583:Interleukin-1beta; D007797:Laminin; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002809:Chondroitin Sulfates; D053148:Caspase 3