Combined transplantation of pancreatic islets and adipose tissue-derived stem cells enhances the survival and insulin function of islet grafts in diabetic mice

Yoshiaki Ohmura, Masahiro Tanemura, Naomasa Kawaguchi, Tomohiko MacHida, Tsukasa Tanida, Takashi Deguchi, Hiroshi Wada, Shogo Kobayashi, Shigeru Marubashi, Hidetoshi Eguchi, Yutaka Takeda, Nariaki Matsuura, Toshinori Ito, Hiroaki Nagano, Yuichiro Doki, Masaki Mori

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Abstract

Background. Overcoming significant loss of transplanted islet mass is important for successful islet transplantation. Adipose tissue-derived stem cells (ADSCs) seem to have angiogenic potential and antiinflammatory properties. We hypothesized that the inclusion of ADSCs with islet transplantation should enhance the survival and insulin function of the islet graft. Methods. Syngeneic ADSCs and allogeneic islets were transplanted simultaneously under the kidney capsules of diabetic C57BL/6J mice. Rejection of the graft was examined by measurement of blood glucose level. Revascularization and inflammatory cell infiltration were examined by immunohistochemistry. Results. Transplantation of 400 islets only achieved normoglycemia with graft survival of 13.6±1.67 days (mean±standard deviation), whereas that of 100 or 200 allogeneic islets never reversed diabetes. Transplantation of 200 islets with 2×105 ADSCs reversed diabetes and significantly prolonged graft survival (13.0±5.48 days). Results of glucose tolerance tests performed on day 7 were significantly better in islets-ADSCs than islets-alone recipients. Immunohistochemical analysis confirmed the presence of insulin-stained islet grafts with well-preserved structure in islets-ADSCs transplant group. Significant revascularization (larger number of von Willebrand factor-positive cells) and marked inhibition of inflammatory cell infiltration, including CD4 and CD8 T cells and macrophages, were noted in the islets-ADSCs transplant group than islets-alone transplant group. Conclusions. Our results indicated that cotransplantation of ADSCs with islet graft promoted survival and insulin function of the graft and reduced the islet mass required for reversal of diabetes. This innovative protocol may allow "one donor to one recipient" islet transplantation.

Original languageEnglish
Pages (from-to)1366-1373
Number of pages8
JournalTransplantation
Volume90
Issue number12
DOIs
Publication statusPublished - Dec 27 2010

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Islets of Langerhans Transplantation
Adipose Tissue
Cell Survival
Stem Cells
Insulin
Transplants
Graft Survival
Graft Rejection
von Willebrand Factor
Glucose Tolerance Test
Inbred C57BL Mouse
Capsules
Blood Glucose
Anti-Inflammatory Agents
Immunohistochemistry
Macrophages
T-Lymphocytes
Kidney

All Science Journal Classification (ASJC) codes

  • Transplantation

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Combined transplantation of pancreatic islets and adipose tissue-derived stem cells enhances the survival and insulin function of islet grafts in diabetic mice. / Ohmura, Yoshiaki; Tanemura, Masahiro; Kawaguchi, Naomasa; MacHida, Tomohiko; Tanida, Tsukasa; Deguchi, Takashi; Wada, Hiroshi; Kobayashi, Shogo; Marubashi, Shigeru; Eguchi, Hidetoshi; Takeda, Yutaka; Matsuura, Nariaki; Ito, Toshinori; Nagano, Hiroaki; Doki, Yuichiro; Mori, Masaki.

In: Transplantation, Vol. 90, No. 12, 27.12.2010, p. 1366-1373.

Research output: Contribution to journalArticle

Ohmura, Y, Tanemura, M, Kawaguchi, N, MacHida, T, Tanida, T, Deguchi, T, Wada, H, Kobayashi, S, Marubashi, S, Eguchi, H, Takeda, Y, Matsuura, N, Ito, T, Nagano, H, Doki, Y & Mori, M 2010, 'Combined transplantation of pancreatic islets and adipose tissue-derived stem cells enhances the survival and insulin function of islet grafts in diabetic mice', Transplantation, vol. 90, no. 12, pp. 1366-1373. https://doi.org/10.1097/TP.0b013e3181ffba31
Ohmura, Yoshiaki ; Tanemura, Masahiro ; Kawaguchi, Naomasa ; MacHida, Tomohiko ; Tanida, Tsukasa ; Deguchi, Takashi ; Wada, Hiroshi ; Kobayashi, Shogo ; Marubashi, Shigeru ; Eguchi, Hidetoshi ; Takeda, Yutaka ; Matsuura, Nariaki ; Ito, Toshinori ; Nagano, Hiroaki ; Doki, Yuichiro ; Mori, Masaki. / Combined transplantation of pancreatic islets and adipose tissue-derived stem cells enhances the survival and insulin function of islet grafts in diabetic mice. In: Transplantation. 2010 ; Vol. 90, No. 12. pp. 1366-1373.
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T1 - Combined transplantation of pancreatic islets and adipose tissue-derived stem cells enhances the survival and insulin function of islet grafts in diabetic mice

AU - Ohmura, Yoshiaki

AU - Tanemura, Masahiro

AU - Kawaguchi, Naomasa

AU - MacHida, Tomohiko

AU - Tanida, Tsukasa

AU - Deguchi, Takashi

AU - Wada, Hiroshi

AU - Kobayashi, Shogo

AU - Marubashi, Shigeru

AU - Eguchi, Hidetoshi

AU - Takeda, Yutaka

AU - Matsuura, Nariaki

AU - Ito, Toshinori

AU - Nagano, Hiroaki

AU - Doki, Yuichiro

AU - Mori, Masaki

PY - 2010/12/27

Y1 - 2010/12/27

N2 - Background. Overcoming significant loss of transplanted islet mass is important for successful islet transplantation. Adipose tissue-derived stem cells (ADSCs) seem to have angiogenic potential and antiinflammatory properties. We hypothesized that the inclusion of ADSCs with islet transplantation should enhance the survival and insulin function of the islet graft. Methods. Syngeneic ADSCs and allogeneic islets were transplanted simultaneously under the kidney capsules of diabetic C57BL/6J mice. Rejection of the graft was examined by measurement of blood glucose level. Revascularization and inflammatory cell infiltration were examined by immunohistochemistry. Results. Transplantation of 400 islets only achieved normoglycemia with graft survival of 13.6±1.67 days (mean±standard deviation), whereas that of 100 or 200 allogeneic islets never reversed diabetes. Transplantation of 200 islets with 2×105 ADSCs reversed diabetes and significantly prolonged graft survival (13.0±5.48 days). Results of glucose tolerance tests performed on day 7 were significantly better in islets-ADSCs than islets-alone recipients. Immunohistochemical analysis confirmed the presence of insulin-stained islet grafts with well-preserved structure in islets-ADSCs transplant group. Significant revascularization (larger number of von Willebrand factor-positive cells) and marked inhibition of inflammatory cell infiltration, including CD4 and CD8 T cells and macrophages, were noted in the islets-ADSCs transplant group than islets-alone transplant group. Conclusions. Our results indicated that cotransplantation of ADSCs with islet graft promoted survival and insulin function of the graft and reduced the islet mass required for reversal of diabetes. This innovative protocol may allow "one donor to one recipient" islet transplantation.

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