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  1. Fulltext Restoring the Angiogenic Capacity of the Human Diabetic Adipose-derived mesenchymal stem cells Primed with Deferoxamine as a Hypoxia Mimetic Agent: Role of HIF-1α
    Tajali R, Eidi A, Ahmadi Tafti H, Pazouki A, Sharifi AM
    Adv Pharm Bull, 2023 Mar;13(2):350-360.
    PMID: 37342375 DOI: 10.34172/apb.2023.021
    Purpose: Insufficient angiogenesis is associated with serious diabetic complications. Recently, adipose-derived mesenchymal stem cells (ADScs) are known to be a promising tool causing therapeutic neovascularization. However, the overall therapeutic efficacy of these cells is impaired by diabetes. This study aims to investigate whether in vitro pharmacological priming with deferoxamine, a hypoxia mimetic agent, could restore the angiogenic potential of diabetic human ADSCs. Methods: Diabetic human ADSCs were treated with deferoxamine and compared to normal and nontreated diabetic ADSCs for the expression of hypoxia inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2) and stromal cell-derived factor-1α (SDF-1α), at mRNA and protein levels, using qRT-PCR, western blotting and ELISA assay. Activities of matrix metalloproteinases (MMPs)-2 and -9 were measured using a gelatin zymography assay. Angiogenic potentials of conditioned media derived from normal, Deferoxamine treated, and non-treated ADSCs were determined by in vitro scratch assay and also three-dimensional tube formation assay. Results: It is demonstrated that deferoxamine (150 and 300 μM) stabilized HIF-1α in primed diabetic ADSCs. At the concentrations used, deferoxamine did not show any cytotoxic effects. In deferoxamine treated ADSCs, expression of VEGF, SDF-1α, FGF-2 and the activity of MMP-2 and MMP-9 were significantly increased compared to nontreated ADSCs. Moreover, deferoxamine increased the paracrine effects of diabetic ADSCs in promoting endothelial cell migration and tube formation. Conclusion: Deferoxamine might be an effective drug for pharmacological priming of diabetic ADSCs to enhance the expression of proangiogenic factors noted via HIF-1α accumulation. In addition, impaired angiogenic potential of conditioned medium derived from diabetic ADSCs was restored by deferoxamine.
  2. Transplantation of adipose derived stem cells in diabetes mellitus; limitations and achievements
    Tajali R, Eidi A, Tafti HA, Pazouki A, Kamarul T, Sharifi AM
    J Diabetes Metab Disord, 2023 Dec;22(2):1039-1052.
    PMID: 37975135 DOI: 10.1007/s40200-023-01280-8
    OBJECTIVES: Diabetes mellitus (DM) is a complex metabolic disease that results from impaired insulin secreting pancreatic β-cells or insulin resistance. Although available medications help control the disease, patients suffer from its complications. Therefore, finding effective therapeutic approaches to treat DM is a priority. Adipose Derived Stem Cells (ADSCs) based therapy is a promising strategy in various regenerative medicine applications, but its systematic translational use is still somewhat out of reach. This review is aimed at clarifying achievements as well as challenges facing the application of ADSCs for the treatment of DM, with a special focus on the mechanisms involved.

    METHODS: Literature searches were carried out on "Scopus", "PubMed" and "Google Scholar" up to September 2022 to find relevant articles in the English language for the scope of this review.

    RESULTS: Recent evidence showed a significant role of ADSC therapies in DM by ameliorating insulin resistance and hyperglycemia, regulating hepatic glucose metabolism, promoting β cell function and regeneration, and functioning as a gene delivery tool. In addition, ADSCs could improve diabetic wound healing by promoting collagen deposition, inhibiting inflammation, and enhancing angiogenesis.

    CONCLUSION: Overall, this literature review revealed the great clinical implications of ADSCs for translating into the clinical setting for the treatment of diabetes. However, further large-scale and controlled studies are needed to overcome challenges and confirm the safety and optimal therapeutic scheme before daily clinical application.

    SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-023-01280-8.

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