Download Role of intracellular level of glutathione on the therapeutic capacity

Role of intracellular level of glutathione on the therapeutic capacity of human
mesenchymal stem cell
Jisun Lim, YongHwan Kim, Seungun Lee, Jinbeom Heo, Hye-Yeon Lee, Hyein Ju & DongMyung Shin
Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of
Medicine, Seoul, Korea
Continuous exposure to oxidative stress during the expansion of mesenchymal stem cells
(MSCs) based on traditional culture techniques results in a progressive loss of proliferative
and differentiation potential. Glutathione (GSH) is an important antioxidant in mammalian
cells, preventing damage to important cellular components caused by reactive oxygen species
(ROS). Here, we show that the MSCs with high content of intracellular GSH have the
enhanced therapeutic potency of MSCs. Employing a newly synthesized fluorescent probe
(FreSH tracer) which exhibit reversible reaction with various thiol-compounds by forming
thioether adduct, Human embryonic stem cells (hES) derived MSC (hES-MSC) were FACS
sorted as GSHhigh verus GSHlow fractions. The hES-MSCs in GSHhigh fraction stimulated
chemoattraction capacity to platelet-derived growth factor (PDGF) and phosphorylation of
both MAPK p42/44 and AKT which is involved in signaling transduction for stem cell
migration. GSHhigh fraction cells also increased self renewal activity in colony forming unit
of fibroblasts assay. As result of gene expression analysis, the hES-MSCs in GSHhigh fraction
highly express the several genes including CXCR4, cMET, PDGF-RA, PDGF-RB, VEGF-R1,
VEGF-R2, ANGPT1, and IDO2. Accordingly, GSHhigh fraction hES-MSCs significantly
improved their therapeutic outcome to alleviate the airway inflammation in an experimental
allergic asthma model. Taken together, these results demonstrates that intracellular level of
GSH is novel indicator to determine the therapeutic efficacy of MSCs.