Myocardial infarction is the most severe form of coronary artery disease and one of the leading causes of death worldwide. This study reports a novel nanotherapeutic engineering approach to enhance the therapeutic effect of mesenchymal stem cells (MSCs) on myocardial ischemia-reperfusion (MI/R) injury. An antioxidant and anti-inflammatory nanotherapeutic agent (TPCD NP) was first prepared. MSCs and TPCD NPs were successfully engineered through endocytosis, and TPCD NP engineering did not affect the stem cell properties of MSCs. MSCs internalized by TPCD NPs (tn-MSCs) are resistant to oxidative stress, cytotoxicity, and apoptosis induced by reactive oxygen species (ROS). Under oxidative stress conditions, tn-MSCs exhibited stronger paracrine activity than MSCs. Correspondingly, tn-MSCs can effectively enhance angiogenesis of endothelial cells under pathological conditions. In addition, tn-MSCs protected cardiomyocytes from ROS-induced cytotoxicity and apoptosis by improving mitochondrial membrane potential and regulating the p53 signaling pathway. In MI/R-injured mice, tn-MSCs survived prolonged survival in the injured heart compared with naïve MSCs. Correspondingly, tn-MSCs more significantly reduced infarct size, improved cardiac function, and promoted cardiac remodeling in MI/R injured mice. Mechanistically, tn-MSCs alleviate MI/R injury by reducing oxidative stress and inflammation, inhibiting cardiomyocyte apoptosis, and promoting cardiac repair. Therefore, tn-MSCs are promising for the treatment of cardiovascular diseases related to oxidative stress and inflammation.

Innovation points:
1. A new nano-therapeutic engineering strategy was developed to significantly improve the effectiveness of stem cell therapy by optimizing the survival microenvironment of stem cells.
2. Successfully achieved the enhancement of stem cell function by nanoparticles while maintaining the basic characteristics of stem cells, providing new ideas for stem cell treatment.
3. Revealed the multiple mechanisms of action of engineered stem cells in treating myocardial reperfusion injury, providing a new strategy for the treatment of cardiovascular diseases.

Inspiration from scientific research work:
1. When developing new treatment strategies, the characteristics of the disease microenvironment should be fully considered and the therapeutic effect should be improved through the synergy of multiple mechanisms.
2. The innovative idea of combining nanotechnology with stem cell treatment provides a new direction to solve the limitations of traditional treatment methods.
3. In-depth study of treatment mechanisms is of great significance in optimizing treatment strategies, and the molecular mechanisms of treatment effects should be explored from multiple levels.

Extension of ideas:
1. This nanoengineering strategy can be extended to other types of stem cells for the treatment of different types of tissue damage and diseases.
2. Antioxidant and anti-inflammatory nanotherapeutic solutions can be expanded to treat other diseases involving oxidative stress and inflammation.
3. This study provides a reference for the development of new cell therapy strategies and can further explore applications in other types of tissue regeneration and repair.
4. Strategies for regulating the stem cell microenvironment can inspire the development of other types of tissue engineering materials and treatment options.

5. This multi-mechanism synergistic treatment idea is worthy of exploration in other disease treatment areas, and is expected to develop more effective treatment options.

Adv. Colloid Interface Sci. (IF 15.9)
Pub Date  : 2024-12-05
DOI : 10.1016/j.cis.2024.103372

Jinping Wang, Guoying Zhang, Kuoran Xing, Baoteng Wang, Yanping Liu, Yuling Xue, Shankui Liu, David Tai Leong