title: The co-transplantation of bone marrow derived mesenchymal stem cells reduced inflammation in intramuscular islet transplantation.
abstract: OBJECTIVE
  Although the muscle is one of the preferable transplant sites in islet transplantation, its transplant efficacy is poor. Here we attempted to determine whether an intramuscular co-transplantation of mesenchymal stem cells (MSCs) could improve the outcome.
  
  
  METHODS
  We co-cultured murine islets with MSCs and then analyzed the morphological changes, viability, insulin-releasing function (represented by the stimulation index), and gene expression of the islets. We also transplanted 500 islets intramuscularly with or without 5 × 105 MSCs to diabetic mice and measured their blood glucose level, the glucose changes in an intraperitoneal glucose tolerance test, and the plasma IL-6 level. Inflammation, apoptosis, and neovascularization in the transplantation site were evaluated histologically.
  
  
  RESULTS
  The destruction of islets tended to be prevented by co-culture with MSCs. The stimulation index was significantly higher in islets co-cultured with MSCs (1.78 ± 0.59 vs. 7.08 ± 2.53; p = 0.0025). In terms of gene expression, Sult1c2, Gstm1, and Rab37 were significantly upregulated in islets co-cultured with MSCs. Although MSCs were effective in the in vitro assays, they were only partially effective in facilitating intramuscular islet transplantation. Co-transplanted MSCs prevented an early inflammatory reaction from the islets (plasma IL-6; p = 0.0002, neutrophil infiltration; p = 0.016 inflammatory area; p = 0.021), but could not promote neovascularization in the muscle, resulting in the failure of many intramuscular transplanted islets to engraft.
  
  
  CONCLUSIONS
  In conclusion, co-culturing and co-transplanting MSCs is potentially useful in islet transplantation, especially in terms of anti-inflammation, but further augmentation for an anti-apoptosis effect and neovascularization is necessary.
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Gumpei
authors: G
authors: Yoshimatsu
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Naoaki
authors: N
authors: Sakata
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Haruyuki
authors: H
authors: Tsuchiya
authors: Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Japan.
authors: Takashi
authors: T
authors: Minowa
authors: Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Japan.
authors: Taro
authors: T
authors: Takemura
authors: Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Japan.
authors: Hiromi
authors: H
authors: Morita
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Tatsuo
authors: T
authors: Hata
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Masahiko
authors: M
authors: Fukase
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takeshi
authors: T
authors: Aoki
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Masaharu
authors: M
authors: Ishida
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Fuyuhiko
authors: F
authors: Motoi
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Takeshi
authors: T
authors: Naitoh
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Integrated Surgery and Oncology, Tohoku University Hospital, Sendai, Japan.
authors: Yu
authors: Y
authors: Katayose
authors: Division of International Cooperation for Disaster Medicine, Tohoku University, Sendai, Japan.
authors: Shinichi
authors: S
authors: Egawa
authors: Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors: Michiaki
authors: M
authors: Unno
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D018929:Cell Culture Techniques; D018920:Coculture Techniques; D003921:Diabetes Mellitus, Experimental; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007249:Inflammation / Q000209:etiology* / Q000473:pathology / Q000628:therapy*; D007515:Islets of Langerhans / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D018919:Neovascularization, Physiologic