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• W3169175046 endingPage "166187" @default.
• W3169175046 startingPage "166187" @default.
• W3169175046 abstract "Deficiency of angiogenic and neurotrophic factors under long term diabetes is known to lead to Schwann cell degeneration, clinically manifested as Diabetic Neuropathy (DN). While the transplantation of exogenous allogenic Mesenchymal Stromal Cells (MSCs) has shown amelioration of DN through paracrine action, it is not known what functional changes occur in endogenous bone-marrow MSCs under chronic diabetes in terms of homing, migration and/or paracrine signalling with reference to the end-point clinical manifestation of Diabetic Neuropathy. We thus aimed at determining the changes in BM-MSCs under Type 1 Diabetes with respect to survival, self-renewal, oxidative status, paracrine activity, intracellular Ca2+ response and migration in response to pathological cytokine/chemokine, in reference to the time-point of decline in Nerve Conduction Velocity (NCV) in a rat model. Within one week of diabetes induction, BM-MSCs underwent apoptosis, and compromised their self-renewal capacity, antioxidant defence mechanism and migration toward cytokine/chemokine; whereas epineurial blood vessel thickening and demyelination resulting in NCV decline were observed only after three weeks. By two- and three-weeks post diabetes induction, BM-MSC apoptosis reduced and proliferative ability was restored; however, their self-renewal, migration and intracellular Ca2+ response toward pathological cytokine/chemokine remained impaired. These results indicate that T1D induced intrinsic functional impairments in endogenous BM-MSCs occur before neuropathy onset. This timeline of functional alterations in BM-MSCs also suggest that treatment strategies that target the bone marrow niche early on may help to modulate BM-MSC functional impairments and thus slow down the progression of neuropathy." @default.
• W3169175046 created "2021-06-22" @default.
• W3169175046 creator A5011732617 @default.
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• W3169175046 date "2021-10-01" @default.
• W3169175046 modified "2023-10-16" @default.
• W3169175046 title "Fundamental changes in endogenous bone marrow mesenchymal stromal cells during Type I Diabetes is a pre-neuropathy event" @default.
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• W3169175046 doi "https://doi.org/10.1016/j.bbadis.2021.166187" @default.
• W3169175046 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34102256" @default.
• W3169175046 hasPublicationYear "2021" @default.
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