Recovery of Human Embryonic Stem Cells-Derived Neural Progenitors Exposed to Hypoxic-Ischemic-Reperfusion Injury by Indi
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ORIGINAL RESEARCH
Recovery of Human Embryonic Stem Cells‑Derived Neural Progenitors Exposed to Hypoxic‑Ischemic‑Reperfusion Injury by Indirect Exposure to Wharton’s Jelly Mesenchymal Stem Cells Through Phosphatidyl‑inositol‑3‑Kinase Pathway Sowmithra Sowmithra1 · Nishtha Kusum Jain1 · Ramesh Bhonde2 · Indrani Datta1 Received: 4 August 2020 / Accepted: 11 November 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Increasing evidence suggests that mesenchymal stem cells(MSCs) have beneficial effects in hypoxic ischemic reperfusion injury, but the underlying mechanisms are unclear. Here, we first examined the effect of OGD reperfusion injury on the vulnerability of human NPs derived from human embryonic stem cells (hESCs) with regard to cell survival and oxidative stress. Cellular deregulation was assessed by measuring glutathione levels, basal calcium and intracellular calcium [Ca2+]i response under KCl stimulation, as well as the key parameters of proliferation, glial progenitor marker expression and migration. Next, the influence of WJ-MSCs in recovering these parameters was evaluated, and the role of Phosphatidylinositol-3-Kinase(PI3K) pathway in actuating the protective effect was assessed. OGD reperfusion injury induced significant increases in cell death, ROS generation, oxidative stress susceptibility and decreased glutathione levels in NPs, accompanied by rises in basal [ Ca2+]i, KCl-induced [Ca2+]i, expression of K+ leak channel(TASK1), and declines in proliferation, migration potential and glial progenitor population. The introduction of WJ-MSCs(after 2 h of reperfusion) through a non-contact method brought about significant improvement in all these cellular parameters as observed after 24hrs, and the PI3K pathway played an important role in the neuroprotection process. Presence of WJ-MSCs increased the expression of survival signals like phosphorylated Akt/Akt and PI3K in the OGD-reperfused NPs. Our data clearly demonstrate for the first time that soluble factors from WJ-MSCs can not only ameliorate survival, proliferation, migration and glial progenitor expression of OGD-reperfused NPs, but also regulate their intracellular Ca2+ response to KCl stimulation and expression of TASK1 through the PI3K pathway. Keywords Oxygen glucose deprivation and reperfusion · Umbilical cord-derived MSCs · In vitro HIE model · Oxidative stress susceptibility · Intracellular calcium · Proliferation · Migration potential · PSA-NCAM · Glial progenitor population Abbreviations Akt1 Protein kinase B ATP Adenosine triphosphate [Ca2+]i Intracellular calcium HIE Hypoxic ischemic encephalopathy MEA Microelectrode array MEF Mouse embryonic fibroblast * Indrani Datta [email protected] 1
Department of Biophysics, National Institute of Mental Health and Neurosciences, Institute of National Importance, Hosur Road, P.B. No. 2900, Bengaluru 560029, Karnataka, India
Dr D.Y. Patil University (DPU), Pune 411018, India
2
MBP Myelin basic protein Mrp-1 Multidrug resistance
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