Introduction and Objective: Mesenchymal Stem Cells’ (MSCs) immunemodulatory & anti-inflammatory actions make them effective Regenerative Medicine tools for Diabetes and its complications. MSCs can be used allogeneically, but patients prefer to use their own cells. Intrinsic MSCs from T1 & T2DM subjects exhibit dysfunctions that may contribute to the comorbidities and inflammation associated with DM. Culture expansion in a non-diabetic milieu does not repair the dysfunctions, suggesting that DM “reprograms” these cells. We and others showed that MSCs from healthy donors are renoprotective and beneficial to patients with DM suggesting they may affect the patient’s own MSCs (see also abstract this meeting).We assessed here whether conditioned medium (CM) from healthy MSCs could restore the functions of MSCs from diabetic patients.Methods: MSCs from healthy, T1 & T2DM donors were culture expanded in low glucose DMEM, or CM from either healthy or T1 DM MSCs. Inflammatory responses were assessed pre and post INFγ exposure (rtPCR & ELISA).Results: IDO-1 and IL6 protein expression are 2-4-fold higher at baseline in T1 & T2DM MSCs vs. control. IDO-1, CCL8, IL6, and IGF1 are elevated 10-40-fold at baseline; IDO1, CXCL-9, CXCL10, IL6, FGF-2, and PD-L1 are elevated 10-200-fold upon stimulation with INFγ in T1 & T2 DM MSCs vs. healthy MSCs. Culture of T1DM & T2DM MSCs in CM from healthy MSCs restores expression of all but IGF1 & IL6 to near normal, while CM from T1DM MSCs does not. When healthy MSCs are cultured in CM from T1DM MSCs, the expression of CXCL10 in healthy MSCs increases by 8.5-fold, suggesting that secreted factors influence these genes’ expression.Conclusion: We demonstrate that healthy MSCs can influence and significantly reset the inflammatory phenotype exhibited by T1 & T2DM MSCs, likely by its secretome. These data identify a novel mechanism whereby administration of healthy MSCs is an effective therapy in T1 & T2DM patients.
A. Gooch: Board Member; SymbioCellTech, LLC. Employee; SymbioCellTech, LLC. Stock/Shareholder; SymbioCellTech, LLC. C. Westenfelder: None.
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