TY - JOUR
T1 - Insulin-Independent Reversal of Type-1 Diabetes following Transplantation of Adult Brown Adipose Tissue Supplemented with IGF-1
AU - Gunawardana, Subhadra C.
AU - Piston, David W.
N1 - Funding Information:
Received 25 June 2019. Revision received 24 August 2019. Accepted 30 August 2019. 1Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO. S.C.G. participated in the research design, performance of research, analysis and interpretation of data, and writing of the article. D.W.P. participated in the research design, interpretation of data, and writing of the article. The authors declare no conflicts of interest. This work was supported by grants from the Diabetes Research Connection (S.C.G.), Washington University Diabetes Center (DK-020579) (S.C.G.), Iacocca Family Foundation (D.W.P.), and Washington University School of Medicine (D.W.P.).
Funding Information:
This work was supported by grants from the Diabetes Research Connection (S.C.G.), Washington University Diabetes Center (DK-020579) (S.C.G.), Iacocca Family Foundation (D.W.P.), and Washington University School of Medicine (D.W.P.). Part of this work was performed by or with the help of the following core facilities: Metabolic Tissue Function Core, Histology Core, and Center for Cellular Imaging at Washington University; Immunomonitoring Laboratory at the Bursky Center for Human Immunology and Immunotherapy Programs at Washington University; Vanderbilt University Hormone Assay Core. Authors are grateful to Dr Peter Bayguinov (Washington University), Dr Zeno Lavagnino (IRCCS Ospedale San Raffaele), and Dr Alessandro Ustione (Washington University) for help with microscopy and image analysis.
Publisher Copyright:
Copyright © 2019 The Author(s).
PY - 2019/11/1
Y1 - 2019/11/1
N2 - Background. As our previous publications show, it is feasible to reverse type 1 diabetes (T1D) without insulin in multiple mouse models, through transplantation of embryonic brown adipose tissue (BAT) in the subcutaneous space. Embryonic BAT transplants result in rapid and long-lasting euglycemia accompanied by decreased inflammation and regenerated healthy white adipose tissue, with no detectable increase in insulin. To translate this approach to human patients, it is necessary to establish practical alternatives for embryonic tissue. Adult adipose tissue transplants or BAT-derived stem cell lines alone fail to reverse T1D. A likely reason is transplant failure resulting from lack of growth factors abundant in embryonic tissue. Adding growth factors may enable transplants to survive and vascularize as well as stimulate adipogenesis and decrease inflammation in the surrounding host tissue. Previous data points to insulin like growth factor 1 (IGF-1) as the most likely candidate. Embryonic BAT abundantly expresses IGF-1, and embryonic BAT transplant recipients exhibit increased plasma levels of IGF-1. Therefore, we tested the ability of temporary administration of exogenous IGF-1 to enable adult BAT transplants to correct T1D. Methods. Fresh BAT from healthy adult CB7BL/6 donors were transplanted in the subcutaneous space of hyperglycemic nonobese diabetic recipients. Exogenous IGF-1 was administered daily for a week following transplant, at 100 µg/kg SC. Results. Adult BAT transplants with IGF-1 supplementation produced rapid long-lasting euglycemia at a 57% success rate, in contrast with no recovery in the control groups who received adult BAT alone, IGF-1 alone, or no treatment. Conclusions. Temporary supplementation with IGF-1 enables adult BAT transplants to correct T1D phenotypes independent of insulin providing a possible route to translate this treatment to human patients.
AB - Background. As our previous publications show, it is feasible to reverse type 1 diabetes (T1D) without insulin in multiple mouse models, through transplantation of embryonic brown adipose tissue (BAT) in the subcutaneous space. Embryonic BAT transplants result in rapid and long-lasting euglycemia accompanied by decreased inflammation and regenerated healthy white adipose tissue, with no detectable increase in insulin. To translate this approach to human patients, it is necessary to establish practical alternatives for embryonic tissue. Adult adipose tissue transplants or BAT-derived stem cell lines alone fail to reverse T1D. A likely reason is transplant failure resulting from lack of growth factors abundant in embryonic tissue. Adding growth factors may enable transplants to survive and vascularize as well as stimulate adipogenesis and decrease inflammation in the surrounding host tissue. Previous data points to insulin like growth factor 1 (IGF-1) as the most likely candidate. Embryonic BAT abundantly expresses IGF-1, and embryonic BAT transplant recipients exhibit increased plasma levels of IGF-1. Therefore, we tested the ability of temporary administration of exogenous IGF-1 to enable adult BAT transplants to correct T1D. Methods. Fresh BAT from healthy adult CB7BL/6 donors were transplanted in the subcutaneous space of hyperglycemic nonobese diabetic recipients. Exogenous IGF-1 was administered daily for a week following transplant, at 100 µg/kg SC. Results. Adult BAT transplants with IGF-1 supplementation produced rapid long-lasting euglycemia at a 57% success rate, in contrast with no recovery in the control groups who received adult BAT alone, IGF-1 alone, or no treatment. Conclusions. Temporary supplementation with IGF-1 enables adult BAT transplants to correct T1D phenotypes independent of insulin providing a possible route to translate this treatment to human patients.
UR - http://www.scopus.com/inward/record.url?scp=85088031945&partnerID=8YFLogxK
U2 - 10.1097/TXD.0000000000000945
DO - 10.1097/TXD.0000000000000945
M3 - Article
AN - SCOPUS:85088031945
SN - 2373-8731
VL - 5
SP - E500
JO - Transplantation Direct
JF - Transplantation Direct
IS - 11
ER -