Treatment of foot disease in patients with type 2 diabetes mellitus using human umbilical cord blood mesenchymal stem cells: response and correction of immunological anomalies.
This study was designed to evaluate the distribution of Tregs/Th17/Th1 cells in type 2 diabetic patients with foot disease before and after human umbilical cord blood mesenchymal stem cell (hUCB-MSCs) transplantation. Fifteen diabetic patients with foot disease under insulin therapy received hUCB-MSC transplantation. The hUCB-MSCs were directly injected into the quadriceps thigh muscles in patients with foot disease (cell quantity at 2 x 10⁶ per point). Physical attributes, blood cytokines, blood glucose and insulin dosage were evaluated before treatment and 1, 2, 4, 8, and 12 weeks thereafter. The ratios of Treg/Th17, Treg/Th1, and Th17/Th1 cells were measured using flow cytometry and their correlation with various cytokines (FoxP3, IL-17, INF-γ, C-RP, TNF-α, and VEGF) was scrutinized. Levels of blood glucose and insulin dosage were significantly reduced in all 15 patients following hUCB-MSC transplantation. The ratios of CD4⁺CD25(hi)FoxP3⁺ Treg/Th17 and CD4⁺CD25(hi)FoxP3⁺ Treg/Th1 cells were significantly increased 4 weeks after transplantation (p < 0.01), while the ratio of Th17/Th1 cells remained unchanged. Serum levels of VEGF peaked at 4 weeks following transplantation. Levels of C-RP and TNF-α were significantly reduced 4 weeks after transplantation. Intriguingly, the ratios of Treg/Th17 were positively correlated with VEGF levels, and were inversely correlated with plasma IL-6 levels. Our data indicated that immune disorders are associated with the development of type 2 diabetes and its complications. Levels of blood glucose and required insulin dosage were reduced after hUCB-MSC transplantation accompanied with improved clinical profiles in diabetic patients. These data favor a role for Treg cells in the onset and progression of T2D.
Department of Endocrine and Metabolic Diseases, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi Province, PR China.
Xiao-Yan
XY
Li
Zhao-Hui
ZH
Zheng
Xue-Yi
XY
Li
Jian
J
Guo
Yan
Y
Zhang
Hui
H
Li
Yang-Wei
YW
Wang
Jun
J
Ren
Zhen-Biao
ZB
Wu
D000328:Adult; D000368:Aged; D036101:Cord Blood Stem Cell Transplantation / Q000379:methods; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D017719:Diabetic Foot / Q000097:blood / Q000276:immunology / Q000628:therapy*; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007273:Injections, Intramuscular; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D013848:Thigh
D016207:Cytokines; D007004:Hypoglycemic Agents; D007328:Insulin