Title:Regulation of ROS/inflammasome Axis is Essential for Cardiac Regeneration in Aging Rats Receiving Transplantation of Mesenchymal Stem Cells
Volume: 19
Issue: 10
Author(s): Wei-Syun Hu, Jing-Yi Chen, Wei-Yu Liao, Chin-Hsien Chang and Tung-Sheng Chen*
Affiliation:
- Graduate Program of Biotechnology and Pharmaceutical Industries, National
Taiwan Normal University, Taipei, 11677, Taiwan
Keywords:
Aging, cardiomyopathy, mesenchymal stem cells, inflammasome, oxidative stress, transplantation.
Abstract:
Background: Aging is a biological and gradual deterioration of function in living organisms.
Aging is one of the risk factors for heart disease.
Objective: Although mesenchymal stem cell transplantation shows potential in heart disease treatment,
the relationship between stem cell-based therapy and oxidative stress/inflammasome axis
regulation remains unclear. This study hypothesized that intervention of stem cells showed protective
effect on heart aging induced by D-galactose through regulation of oxidative stress/inflammasome
axis.
Methods: An aging animal model was designed to test the above hypothesis. Experimental animals
were divided into three groups, including Sham, D-gal (aging rats induced by d-galactose),
and D-gal+WJSC (aging rats receiving mesenchymal stem cells).
Results: Compared to the Sham, the experimental results indicate that structural alteration (HE
stain and Masson’s Trichrome stain), oxidative stress elevation (increase of TBARS level, expression
of gp-91 and suppression of Sirt-1 as well as SOD2), increase of aging marker p53, suppression
of cardiogenesis marker Troponin T, and inflammasome related protein markers expression
(NLRP3, caspase-1 and IL-1 beta) were significantly observed in D-gal. In contrast, all pathological
pathways were significantly improved in D-gal+WJSC when compared to D-gal. In addition,
migration of stem cells to aging heart tissues was observed in the D-gal+WJSC group.
Conclusion: These findings suggest that mesenchymal stem cell transplantation effectively ameliorates
aging hearts through oxidative stress/inflammasome axis regulation. The results from this
study provide clinical potential for stem cell-based therapy in the treatment of aging hearts.