Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation.
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.
Wen
Yanting
Y
Department of Hematology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321, Zhongshan Road, Nanjing 210008, China.
Ouyang
Jian
J
Yang
Rong
R
Chen
Junhao
J
Liu
Yong
Y
Zhou
Xiaojun
X
Burt
Richard K
RK
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D016026:Bone Marrow Transplantation; D015704:CD4 Antigens / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D012038:Regeneration; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome
D001786:Blood Glucose; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007328:Insulin; D012333:RNA, Messenger