title: Transplantation of co-aggregates of Sertoli cells and islet cells into liver without immunosuppression.
abstract: BACKGROUND
  Transplantation of islets of Langerhans (islets) was used to treat insulin-dependent diabetes mellitus. However, islet grafts must be maintained by administration of immunosuppressive drugs, which can lead to complications in the long term. An approach that avoids immunosuppressive drug use is desirable.
  
  
  METHODS
  Co-aggregates of Sertoli cells and islet cells from BALB/c mice that were prepared by the hanging drop method were transplanted into C57BL/6 mouse liver through the portal vein as in human clinical islet transplantation.
  
  
  RESULTS
  The core part of the aggregates contained mainly Sertoli cells, and these cells were surrounded by islet cells. The co-aggregates retained the functions of both Sertoli and islet cells. When 800 co-aggregates were transplanted into seven C57BL/6 mice via the portal vein, six of seven recipient mice demonstrated quasi-normoglycemia for more than 100 days.
  
  
  CONCLUSIONS
  The hanging drop method is suitable for preparing aggregates of Sertoli and islet cells for transplantation. Notably, transplantation of these allogeneic co-aggregates into mice with chemically induced diabetes via the portal vein resulted in long-term graft survival without systemic immunosuppression.
authors.affiliation: 1 Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan. 2 Radioisotope Research Center, Kyoto University, Kyoto, Japan. 3 Department of Immunology, Genetics and Pathology (IGP), Uppsala University, Uppsala, Sweden. 4 Address correspondence to: Hiroo Iwata, Ph.D., Department of Reparative Materials, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-Cho, Shogoin, Sakyo-Ku, Kyoto, 606-8507, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Takemoto
authors.forename: Xibao
authors.initials: X
authors.lastname: Liu
authors.forename: Kento
authors.initials: K
authors.lastname: Takii
authors.forename: Yuji
authors.initials: Y
authors.lastname: Teramura
authors.forename: Hiroo
authors.initials: H
authors.lastname: Iwata
mesh_terms: D028341:Activins / Q000737:chemistry; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000628:therapy; D003922:Diabetes Mellitus, Type 1 / Q000628:therapy*; D006085:Graft Survival; D007108:Immune Tolerance; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology* / Q000276:immunology; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000379:methods*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011169:Portal Vein / Q000473:pathology; D012708:Sertoli Cells / Q000166:cytology*
chemical_list: D007166:Immunosuppressive Agents; D007328:Insulin; C422405:activin A; D028341:Activins