title: Reversal of diabetes by the creation of neo-islet tissues into a subcutaneous site using islet cell sheets.
abstract: BACKGROUND
  There remains a paucity of therapeutic approaches to completely treat diabetes mellitus. This study was designed to develop a dispersed islet cell-based tissue engineering approach to engineer functional neo-islet tissues in the absence of traditional bioabsorbable scaffold matrices.
  
  
  METHODS
  Specialized coated plastic dishes were prepared by covalently immobilizing a temperature-responsive polymer, poly(N-isopropylacrylamide), onto the plastic followed by coating with laminin-5. Dispersed rat islet cells were plated on the laminin-5-poly(N-isopropylacrylamide) dishes. After 2 days of culturing, islet cells were harvested as a uniformly connected tissue sheet by lowering the culture temperature from 37°C to 20°C for 30 min. Two harvested islet cell sheets were transplanted into the subcutaneous space of streptozotocin-induced diabetic severe combined immunodeficiency (SCID) mice to engineer neo-islet tissues in vivo. Therapeutic effects were investigated after the tissue engineering procedures.
  
  
  RESULTS
  In all of the diabetic SCID mice transplanted with the islet sheets, serum hyperglycemia was successfully reverted to a steady normoglycemic level. The recipient SCID mice demonstrated positive for serum rat C-peptide and elevated serum insulin levels. Moreover, the islet cell sheet-transplanted SCID mice demonstrated rapid glucose clearance and return of serum glucose levels after intraperitoneal glucose tolerance test. Histological examination revealed that the transplanted islet cell sheets were structured as flat clusters of islet tissues in which an active vascular network manifested within and surrounding the newly formed tissues.
  
  
  CONCLUSIONS
  This study describes a new proof-of-concept therapeutic approach to engineer functional neo-islet tissues for the treatment of type 1 diabetes mellitus.
authors: Department of Surgery, Fukushima Medical University, Fukushima, Japan.
authors: Takahiro
authors: T
authors: Saito
authors: Kazuo
authors: K
authors: Ohashi
authors: Rie
authors: R
authors: Utoh
authors: Hirofumi
authors: H
authors: Shimizu
authors: Kazuya
authors: K
authors: Ise
authors: Hiroyuki
authors: H
authors: Suzuki
authors: Masayuki
authors: M
authors: Yamato
authors: Teruo
authors: T
authors: Okano
authors: Mitsukazu
authors: M
authors: Gotoh
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000097:blood; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000139:chemically induced / Q000601:surgery*; D004195:Disease Models, Animal; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000166:cytology / Q000601:surgery*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D051381:Rats; D011917:Rats, Inbred Lew; D013311:Streptozocin / Q000009:adverse effects; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007328:Insulin; D013311:Streptozocin