Time point is important for effects of syngeneic bone marrow transplantation for type 1 diabetes in mice.
OBJECTIVE
Autologous hematopoietic stem cell transplantation (HSCT) has recently become a novel therapy for patients with new-onset type 1 diabetes (T1D). However, the optimal time points for HSCT are still unknown.


METHODS
By using multiple low-dose streptozotocin (STZ)-induced T1D mice models, we performed syngeneic bone marrow transplantation (syn-BMT) in diabetic mice at various time points new-onset day 3 (n = 12); new-onset day 10 (n = 13); later-onset day 20 (n = 12); and day 40 (n = 7), respectively. At 120 days after syn-BMT, we examined pancreata histology, serum insulin, and CD4(+)CD25(+)FoxP3(+) T regulatory lymphocytes (Tregs).


RESULTS
Our previous results showed that syn-BMT can overcome diabetes when performed on day 10, but not at day 40. Our new data showed BMT only attenuated diabetes when done on day 3 or day 20. Moreover, the percentage of Tregs in the spleen correlated with the attenuation of hyperglycemia.


CONCLUSIONS
These results indicated that syn-BMT should be performed, when diabetes is neither too new-onset nor too late-stage. Tregs represent one mechanism for syn-BMT-induced restoration of immune tolerance in STZ-diabetic mice.
Wen
Y
Y
Department of Hematology, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.
Ouyang
J
J
Li
W
W
Chen
J
J
Liu
Y
Y
Meng
L
L
Zhang
H
H
Zhou
X
X
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000379:methods*; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D005434:Flow Cytometry; D005500:Follow-Up Studies; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010179:Pancreas / Q000166:cytology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014182:Transplantation, Autologous / Q000379:methods; D014185:Transplantation, Isogeneic / Q000379:methods*
D001786:Blood Glucose; D007328:Insulin