Translational Research
Volume 155, Issue 5 , Pages 211-216, May 2010

New type of human blood stem cell: a double-edged sword for the treatment of type 1 diabetes

  • Yong Zhao

      Affiliations

    • Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Ill
    • Corresponding Author InformationReprint requests: Yong Zhao, Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, 1819 W. Polk Street, Chicago, Ill 60612
    • Yong Zhao, MD, PhD is an Assistant Professor of Medicine, Section of Endocrinology, Diabetes & Metabolism, University of Illinois at Chicago.
  • ,
  • Brian Lin

      Affiliations

    • Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Ill
  • ,
  • Michael Dingeldein

      Affiliations

    • Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Ill
  • ,
  • Chengshan Guo

      Affiliations

    • Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Ill
  • ,
  • David Hwang

      Affiliations

    • Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Illinois at Chicago, Chicago, Ill
  • ,
  • Mark J. Holterman

      Affiliations

    • Department of Surgery, University of Illinois at Chicago, Chicago, Ill

Received 1 November 2009; received in revised form 12 January 2010; accepted 13 January 2010. published online 15 February 2010.

Type 1 diabetes (T1D) is an autoimmune disease caused by an autoimmune destruction of pancreatic islet insulin-producing cells. Autoimmunity and shortage of insulin-producing cells are 2 key issues for the treatment of T1D. To cure T1D in a comprehensive manner, both issues need to be addressed simultaneously. Not only must the islet cells be replaced, the patient's immune system also must be dealt with. Regulatory T cells (Tregs) play a crucial role in maintaining homeostasis and self-tolerance through their inhibitory impacts on autoreactive effector T cells. We identified a novel type of stem cells from human umbilical cord blood, designated cord blood stem cells (CB-SC), which may be able to address immune modulation of the autoimmune process and allow for β-cell replacement. We are the first group using CB-SC to correct functional defects of CD4+CD62L+ Tregs, leading to a reversal of overt diabetes in an autoimmune-caused diabetic NOD mouse model. Notably, treatment with CB-SC-modulated CD4+CD62L+ Tregs (mCD4CD62L Tregs) simultaneously can overcome the autoimmunity via systemic and local immune modulations and the shortage of insulin-producing cells via stimulating the β-cell regeneration. These new stem cells will offer a promising avenue for the development of powerful autologous therapeutic products for prevention and reversal of T1D.

Abbreviations: CB-SC, cord blood stem cells, ES, embryonic stem, IL-10, interleukin-10, NO, nitric oxide, NOD, non-obese diabetic, PB-IPC, peripheral blood-derived insulin-producing cells, SSEA, stage-specific embryonic antigen, T1D, type 1 diabetes, TGF- β 1, transforming growth factor-β 1, Tregs, regulatory T cells

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PII: S1931-5244(10)00010-1

doi:10.1016/j.trsl.2010.01.003

Translational Research
Volume 155, Issue 5 , Pages 211-216, May 2010