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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.

Abstract
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.
AuthorsXiao-Yan Li, Zhao-Hui Zheng, Xue-Yi Li, Jian Guo, Yan Zhang, Hui Li, Yang-Wei Wang, Jun Ren, Zhen-Biao Wu
JournalCurrent pharmaceutical design (Curr Pharm Des) Vol. 19 Issue 27 Pg. 4893-9 ( 2013) ISSN: 1873-4286 [Electronic] United Arab Emirates
PMID23343120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Cytokines
  • Hypoglycemic Agents
  • Insulin
Topics
  • Adult
  • Aged
  • Cord Blood Stem Cell Transplantation (methods)
  • Cytokines (blood)
  • Diabetes Mellitus, Type 2 (complications, drug therapy)
  • Diabetic Foot (blood, immunology, therapy)
  • Drug Monitoring
  • Female
  • Humans
  • Hypoglycemia (prevention & control)
  • Hypoglycemic Agents (administration & dosage, therapeutic use)
  • Injections, Intramuscular
  • Insulin (administration & dosage, therapeutic use)
  • Male
  • Mesenchymal Stem Cell Transplantation (methods)
  • Middle Aged
  • T-Lymphocytes, Regulatory (immunology)
  • Th1 Cells (immunology)
  • Th17 Cells (immunology)
  • Thigh

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