The effect of Trimetazidine and Diazoxide on immunomodulatory activity of human embryonic stem cell-derived mesenchymal stem cell secretome

• Published in: Tissue & cell Vol. 49; no. 5; pp. 597 - 602
• Main Authors: Jahandideh, Saeed, Maghsood, Faezeh, Ghahhari, Nastaran Mohammadi, Lotfinia, Majid, Mohammadi, Mohammad, Johari, Behrooz, Kadivar, Mehdi
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.10.2017; Elsevier Science Ltd
• Subjects: Cell cycle; Cell growth; Chemokines; Conditioning; Culture Media, Conditioned; Cytokines; Diazoxide; Diazoxide - pharmacology; Embryo cells; Embryonic stem cell-derived mesenchymal stem cells; Embryonic Stem Cells - drug effects; Enzyme-linked immunosorbent assay; Extracellular matrix; Growth factors; Hematopoiesis; Humans; Immune response; Immune system; Immunomodulation; Immunosuppressive agents; Interleukin 10; Interleukin-10 - secretion; Interleukin-1beta - secretion; Leukocytes (mononuclear); Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - secretion; Lipopolysaccharides; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stromal Cells - drug effects; Mesenchyme; Peripheral blood mononuclear cells; Pharmacology; Preconditioning; Proteins; Proteome - drug effects; Proteomes; Regeneration; Secretome; Stem cells; Therapeutic applications; Transplantation; Trimetazidine; Trimetazidine - pharmacology; Tumor Necrosis Factor-alpha - secretion; Tumor necrosis factor-α; Vascularization; Vasodilator Agents - pharmacology; Secretome; Diazoxide; Preconditioning; Trimetazidine; Embryonic stem cell-derived mesenchymal stem cells
• ISSN: 0040-8166; 1532-3072; 1532-3072
• DOI: 10.1016/j.tice.2017.08.003

•Thanks to the greater expansion capability compared to regular MSCs, ESC-MSCs are better candidate for secretome therapy.•TMZ and DZ- ESC-MSCs conditioned medium increased the secretion of IL-10, TNFα and IL-1β from LPS- induced PBMCs.•TMZ and DZ can be used to modulate the immune-activity effects of the human ESC-MSCs secretome. Comprehensive proteome profiling of the factors secreted by mesenchymal stem cells (MSCs), referred to as secretome, revealed that it consists of cytokines, chemokines, growth factors, extracellular matrix proteins, and components of regeneration, vascularization, and hematopoiesis pathways. Harnessing this MSC secretome for therapeutic applications requires the optimization of production of secretary molecules. A variety of preconditioning methods have been introduced, which subject cells to stimulatory molecules to create the preferred response and stimulate persistent effects. Pharmacological preconditioning uses small molecules and drugs to increase survival of MSCs after transplantation or prolong release of effective secretary factors such as cytokines that improve immune system responses. In this study, we investigated the effect of secretome of human embryonic-derived mesenchymal stem cells (hESC-MSCs) preconditioned with Trimetazidine (TMZ) and Diazoxide (DZ) on immunomodulatory efficiency of these cells in LPS-induced peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from human peripheral blood and treated with concentrated hESC-MSC-derived conditioned medium and then, the secreted levels of IL-10, TNFα and IL-1β were assessed by ELISA after induction with LPS. The results showed that TMZ and DZ-conditioned medium significantly enhanced immunomodulatory potential of hESC-MSCs by increasing the secretion of IL-10, TNFα and IL-1β from LPS- induced PBMCs. We also found that hESC-MSCs did not secrete mentioned cytokines prior to or after the preconditioning with TMZ and DZ. In conclusion, our results implied that TMZ and DZ can be used to promote the immunomodulatory effects of hESC-MSC secretome. It is obvious that for applying of these findings in clinical demands, the potency of different pre-conditioned MSCs secretome on immune response needs to be more clarified.