Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation

Yanting Wen, Jian Ouyang*, Rong Yang, Junhao Chen, Yong Liu, Xiaojun Zhou, Richard K. Burt

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n = 20) and recipients (n = 20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P < 0.001), maintain normal blood insulin levels (P < 0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P < 0.01), increased Foxp3 mRNA expression (P < 0.01) and increased Foxp3 protein expression (P < 0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.

Original languageEnglish (US)
Pages (from-to)282-287
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume374
Issue number2
DOIs
StatePublished - Sep 19 2008

Keywords

  • CD4+CD25+FoxP3+ regulatory T cells
  • Immunologic tolerance
  • Syngeneic bone marrow transplantation
  • Type 1 diabetes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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