title: Xenograft of microencapsulated sertoli cells reverses T1DM in NOD mice by inducing neogenesis of beta-cells.
abstract: BACKGROUND
  Sertoli cells (SCs) provide an immunoprotective environment to pancreatic islet grafts for treatment of insulin-dependent diabetes. Aim of this work was to verify whether intraperitoneal graft of SCs, enveloped in barium alginate-based microcapsules, would reverse overt spontaneous diabetes in nonobese diabetic (NOD) mice by eliciting generation of newly formed functional islets β-cells.
  
  
  METHODS
  Microcapsules were prepared, according to our method, by a mono air-jet device system and thereafter examined as far as (a) SC morphology by light microscopy; (b) SC viability by fluorescence microscopy; (c) SC in vitro function; and (d) SC in vivo function, as quoted by diabetes reversal in the NOD mice, were concerned.
  
  
  RESULTS
  SCs containing microcapsules exhibited excellent morphology, viability, and function, and when grafted into the NOD's, they induced stable reversion of the disease in 81% of the cases. The treated mice showed dramatic increase in regulatory T lymphocytes (Treg) when compared with control diabetic NOD's treated with empty capsules only. Histologic examination of pancreata retrieved from the SC-transplanted animals showed total disappearance of insulitis, with appearance of new islets, as shown by immunocytochemistry; restored ability of the islets to produce insulin, glucagon, and somatostatin; and finally, increased expression of key transcriptional factors such as neurogenin 3.
  
  
  CONCLUSIONS
  SCs, enveloped in barium alginate-based microcapsules, showed no long-term loss of their functional and morphological properties in vitro or in vivo. Xenograft of microencapsulated-SC-induced reversal of spontaneous diabetes in the majority of the treated NOD mice, based on SC-related powerful immunomodulatory and pro-β-cell regeneration properties.
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Luca
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.forename: Mario
authors.initials: M
authors.lastname: Calvitti
authors.forename: Francesca
authors.initials: F
authors.lastname: Mancuso
authors.forename: Claudio
authors.initials: C
authors.lastname: Nastruzzi
authors.forename: Iva
authors.initials: I
authors.lastname: Arato
authors.forename: Giulia
authors.initials: G
authors.lastname: Falabella
authors.forename: Ursula
authors.initials: U
authors.lastname: Grohmann
authors.forename: Ennio
authors.initials: E
authors.lastname: Becchetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Puccetti
authors.forename: Riccardo
authors.initials: R
authors.lastname: Calafiore
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000097:blood; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005136:Eye Proteins / Q000235:genetics; D005934:Glucagon / Q000097:blood / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D007330:Insulin Antibodies / Q000097:blood; D050417:Insulin-Secreting Cells / Q000473:pathology* / Q000502:physiology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D009419:Nerve Tissue Proteins / Q000235:genetics; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D000073718:Pancreatitis-Associated Proteins; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D012708:Sertoli Cells / Q000166:cytology / Q000637:transplantation*; D013004:Somatostatin / Q000097:blood; D013737:Testis / Q000166:cytology; D015534:Trans-Activators / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D001323:Autoantibodies; D051792:Basic Helix-Loop-Helix Proteins; D001786:Blood Glucose; D005136:Eye Proteins; D005934:Glucagon; D018398:Homeodomain Proteins; D007328:Insulin; D007330:Insulin Antibodies; D009419:Nerve Tissue Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D019009:Proto-Oncogene Proteins c-kit; D012097:Repressor Proteins; D013004:Somatostatin; D015534:Trans-Activators; C501008:Neurod1 protein, mouse; C407737:Neurog3 protein, mouse; C110218:Pax4 protein, mouse; C000605732:Pax6 protein, mouse; C490253:Reg3b protein, mouse; C084010:pancreatic and duodenal homeobox 1 protein