Computational and in vitro validation of cardiogenic induction of quercetin on adipose-derived mesenchymal stromal cells through the inhibition of Wnt and non-Smad-dependent TGF-ß pathways.

Exploiting human mesenchymal stem cells (hMSCs) was proposed as a promising therapeutic approach for cardiovascular disease due to their capacity to differentiate into cardiac cells. Though modulation of the intracellular signaling pathways dominantly WNT/ß catenin and transforming growth factor-ß (TGF-ß) have been reported to promote differentiation of hMSCs into cardiomyocytes in the prevailing literature, a safe and reproducible system for their clinical application has not yet turned into reality. In the present study, the molecular docking-based strategy was first applied for evaluating the potency of some natural phenolic compounds in the modulation of Wnt and TGF-ß signaling pathways using a vital class of crystallographic protein structures of WNT signaling regulators such as Frizzled, Disheveled, GSK3-ß, ß-catenin, LRP 5/6 extracellular domain, Tankyrase and their variety of active pockets. Then, the impacts of plant-derived chemical compounds on the regulation of the relevant signals for the differentiation of hMSCs into the definitive mesoderm lineage and cardiac progenitors were assessed in vitro. Data obtained revealed the synergistic activity of Wnt and TGF-ß superfamily to direct cardiac differentiation in human cardiogenesis by comparing cardiac gene expression in the presence and absence of the TGF-ß inhibitors. We found that the inhibitory effect of canonical Wnt/ß-catenin is sufficient to cause proper cardiomyocyte differentiation, but the TGF-ß pathway plays a vital role in enhancing the expression of the cardiomyocyte-specific marker (cTnT). It was found that quercetin, a p38MAPK inhibitor with the high energy dock to the active pocket of Wnt receptors, promotes cardiac differentiation via the inhibition of both Wnt and non-Smad TGF-ß pathways. Altogether, data presented here can contribute to the development of a feasible and efficient cardiac differentiation protocol as an "off-the-shelf" therapeutic source using novel natural agents for cardiac repair or regeneration.

Adipose-derived mesenchymal stem cells ameliorate lung epithelial injury through mitigating of oxidative stress in mustard lung.

Aim: We investigated potential efficacy of autologous adipose-derived mesenchymal stem cell (MSC) on oxidative stress (OS) and airway remodeling in patients with chronic mustard lung. Patients & methods: Ten patients received 100 × 106 cells every 20 days for 4 injections over a 2-month period. Results: A gradual improvement was observed for 6 min walk test scores, pulmonary function tests and respiratory quality after MSCs therapy. A significant decrease was found for the mean levels of Mucin-1 protein (KL-6; p = 0.022) and Clara cell protein 16 (CC16; p = 0.005). Antioxidants had a tendency to be higher after each injection. Conclusion: Our findings revealed that MSCs therapy can be safely used for improvement of lung injury and regeneration in these patients without adverse effects. Trial registration number: NCT02749448 (ClinicalTrials.gov).