title: Allogeneic bone marrow cocultured with human islets significantly improves islet survival and function in vivo.
abstract: BACKGROUND
  A significant barrier to islet transplantation is the rapid loss of human islet function in vivo. The present study evaluates whether bone marrow (BM) could be used to support human islet survival and function in vivo.
  
  
  METHODS
  We cocultured human islets and BM for 3 weeks before transplantation into the left subrenal capsule of diabetic severe combined immunodeficient mice.
  
  
  RESULTS
  The cocultured human islets before transplantation demonstrated improved viability, increased size, and migration capacity in vitro. After 4 months, animals transplanted with precultured BM/islets exhibited euglycemia and detectable human insulin levels (157 μU/mL), whereas no human insulin was detected in the islet-only transplantation group. Furthermore, the removal of the transplants on day 126 resulted in hyperglycemia, indicating that the reduction of blood glucose was dependent on the transplants. Diabetic mice transplanted with BM/islets demonstrated the longest survival period (130 vs. 40 days for those with islet-only transplants). The transplanted BM/islets showed signs of vascularization and migration from the renal capsule into medulla.
  
  
  CONCLUSIONS
  Our results suggest that BM precultured with human islets may enhance the survival and function of transplanted islets, thus significantly improving the therapeutic efficacy of islet transplantation for type 1 diabetes.
authors: Roger Williams Medical Center, Boston University, Providence, RI 02908, USA. .
authors: John Z Q
authors: JZ
authors: Luo
authors: Fang
authors: F
authors: Xiong
authors: A Samer
authors: AS
authors: Al-Homsi
authors: Camillo
authors: C
authors: Ricordi
authors: Luguang
authors: L
authors: Luo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology*; D002470:Cell Survival; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000628:therapy*; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology*; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D013997:Time Factors; D014184:Transplantation, Homologous
chemical_list: D001786:Blood Glucose; D005456:Fluorescent Dyes