Biodritin microencapsulated human islets of Langerhans and their potential for type 1 diabetes mellitus therapy.
BACKGROUND
Microencapsulation of pancreatic islets with polymeric compounds constitutes an attractive alternative therapy for type 1 diabetes mellitus. The major limiting factor is the availability of a biocompatible and mechanically stable polymer. We investigated the potential of Biodritin, a novel polymer constituted of alginate and chondroitin sulfate, for islet microencapsulation.


METHODS
Biodritin microcapsules were obtained using an air jet droplet generator and gelated with barium or calcium chloride. Microencapsulated rat insulinoma RINm5F cells were tested for viability using the [3-(4,5-dimetyl-thiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide] [MTT] colorimetric assay. Microencapsulated rat pancreatic islets were coincubated with macrophages derived from mouse peritoneal liquid to assess the immunomodulatory potential of the microcapsules, using quantitative real time-PCR (qPCR). Biodritin biocompatibility was demonstrated by subcutaneous injection of empty microcapsules into immunocompetent Wistar rats. Insulin secretion by microencapsulated human pancreatic islets was evaluated using an electrochemoluminescent assay. Microencapsulated human islets transplanted into chemically induced diabetic mice were monitored for reversal of hyperglycemia.


RESULTS
The metabolic activity of microencapsulated RINm5F cells persisted for at least 15 days. Interleukin-1beta expression by macrophages was observed during coculture with islets microencapsulated with Biodritin-CaCl2, but not with Biodritin-BaCl2. No statistical difference in glucose-stimulated insulin secretion was observed between nonencapsulated and microencapsulated islets. Upon microencapsulated islet transplantation, the blood glucose level of diabetic mice normalized; they remained euglycemic for at least 60 days, displaying normal oral glucose tolerance tests.


CONCLUSIONS
This study demonstrated that Biodritin can be used for islet microencapsulation and reversal of diabetes; however, further investigations are required to assess its potential for long-term transplantation.
Campos-Lisbôa
A C V
AC
NUCEL, Cell and Molecular Therapy Center, University of São Paulo, São Paulo, Brazil.
Mares-Guia
T R
TR
Grazioli
G
G
Goldberg
A C
AC
Sogayar
M C
MC
D000464:Alginates / Q000494:pharmacology*; D000818:Animals; D001672:Biocompatible Materials; D002214:Capsules; D045744:Cell Line, Tumor; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D018920:Coculture Techniques; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007340:Insulinoma; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008264:Macrophages / Q000166:cytology / Q000502:physiology; D051381:Rats
D000464:Alginates; D001672:Biocompatible Materials; C529638:Biodritin; D002214:Capsules; D007328:Insulin; D002809:Chondroitin Sulfates