PARKIN overexpression in human mesenchymal stromal cells from Wharton's jelly suppresses 6-hydroxydopamine-induced apoptosis: Potential therapeutic strategy in Parkinson's disease

Cytotherapy
A R Bonilla-PorrasM Jimenez-Del-Rio

Abstract

Stem cell transplantation is an excellent option for regenerative or replacement therapy. However, deleterious microenvironmental and endogenous factors (e.g., oxidative stress) compromise ongoing graft survival and longevity. Therefore, (transient or stable) genetically modified cells may be reasonably thought to resist oxidative stress-induced damage. Genetic engineering of mesenchymal stromal cells (MSCs) obtained from Wharton's jelly tissue may offer some therapeutic potential. PARKIN is a multifunctional ubiquitin ligase able to protect dopaminergic cells against stress-related signaling. We, therefore, evaluated the effect of the neurotoxicant 6-hydroxydopamine (6-OHDA) on regulated cell death signaling in MSCs and investigated whether overexpression of PARKIN in MSCs was capable of modulating the effect of 6-OHDA. We transiently transfected Wharton's jelly-derived MSCs with an mCherry-PARKIN vector using the Lipofectamine LTX method. Naïve MSCs and MSCs overexpressing PARKIN were exposed to increasing concentrations of 6-OHDA. We used light and fluorescence microscopy, flow cytometry, immunocytochemistry staining, in-cell Western and Western blot analysis. After 12-24 h of 6-OHDA exposure, we detected dichlorofluorescein...Continue Reading

Citations

Aug 14, 2019·Scientific Reports·Lyudmila KovalchukeLloyd A Greene
Sep 26, 2020·Frontiers in Cell and Developmental Biology·Patricia Kauanna Fonseca DamascenoMilena Botelho Pereira Soares
Aug 4, 2020·Chemical & Pharmaceutical Bulletin·Huibo LeiWeidong Zhang
Feb 20, 2020·Current Pharmaceutical Biotechnology·Hadi RajabiDavoud Sanajou
Mar 3, 2021·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Milad Ahani-NahayatiAli Hassanzadeh
May 4, 2021·Frontiers in Veterinary Science·Fariborz NowzariAmin Tamadon

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