TGF-β engineered mesenchymal stem cells (TGF-β/MSCs) for treatment of Type 1 diabetes (T1D) mice model

Int Immunopharmacol. 2017 Mar:44:191-196. doi: 10.1016/j.intimp.2017.01.019. Epub 2017 Jan 19.

Abstract

Objective: Mesenchymal stem cells (MSCs) are advantageous candidates for cell therapy of Type 1 diabetes (T1D). Considering immunomodulatory effect of MSC, in this study, we engineered MSCs with TGF-β gene to increase MSC potency for T1D therapy in mouse model.

Materials and methods: Two plans were designed for prevention and treatment of diabetes, respectively. In both of them, MSCs were injected i.v. and then, the diabetes features including serum insulin, blood glucose, glucose tolerance, splenocytes proliferation, and IL-4/IFN-γ production were evaluated.

Results: TGF-β/MSCs treatment program resulted in the restoration of serum glucose after 3weeks, while prevention program could delay diabetes progression for two weeks. TGF-β/MSCs treatment elevated the levels of serum insulin and Th2 cytokine shift on 5th week after start of treatment. TGF-β/MSCs (and MSCs alone) could also diminish body weight and enhance mice survival comparing to untreated diabetic mice.

Conclusion: Engineered TGF-β/MSCs could restore some T1D features, including the regulation of adverse immune responses and could be potent tools for cell therapy of T1D comparing MSCs alone.

Keywords: Cell therapy; Mesenchymal stem cell; TGF-β; Type 1 diabetes.

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cells, Cultured
  • Cytokines / metabolism
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetes Mellitus, Type 1 / immunology
  • Diabetes Mellitus, Type 1 / therapy*
  • Genetic Engineering
  • Humans
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Th1-Th2 Balance
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • Blood Glucose
  • Cytokines
  • Transforming Growth Factor beta