Yue Tian, Zhang Wentai, Pei Haifeng, Danzeng Dunzhu, He Jian, Yang Jiali, Luo Yong, Zhang Zhen, Xiong Shiqiang, Yang Xiangbo, Ji Qisen, Yang Zhilu, Hou Jun
Department of Cardiology, The Third People's Hospital of Chengdu/Affiliated Hospital of Southwest Jiaotong University, Chengdu Institute of Cardiovascular Disease, Chengdu, Sichuan, 610031, China.
Dongguan Key Laboratory of Smart Biomaterials and Regenerative Medicine, The Tenth Affiliated Hospital, Southern Medical University, Dongguan, Guangdong, 523000, China.
Bioact Mater. 2024 Sep 4;42:270-283. doi: 10.1016/j.bioactmat.2024.08.038. eCollection 2024 Dec.
Mesenchymal stem cells (MSCs) have demonstrated significant therapeutic potential in heart failure (HF) treatment. However, their clinical application is impeded by low retention rate and low cellular activity of MSCs caused by high inflammatory and reactive oxygen species (ROS) microenvironment. In this study, monascus pigment (MP) nanoparticle (PPM) was proposed for improving adverse microenvironment and assisting in transplantation of bone marrow-derived MSCs (BMSCs). Meanwhile, in order to load PPM and reduce the mechanical damage of BMSCs, injectable hydrogels based on Schiff base cross-linking were prepared. The PPM displays ROS-scavenging and macrophage phenotype-regulating capabilities, significantly enhancing BMSCs survival and activity in HF microenvironment. This hydrogel demonstrates superior biocompatibility, injectability, and tissue adhesion. With the synergistic effects of injectable, adhesive hydrogel and the microenvironment-modulating properties of MP, cardiac function was effectively improved in the pericardial sac of rats. Our results offer insights into advancing BMSCs-based HF therapies and their clinical applications.
间充质干细胞（MSCs）在心力衰竭（HF）治疗中已显示出显著的治疗潜力。然而，高炎症和活性氧（ROS）微环境导致的MSCs低保留率和低细胞活性阻碍了它们的临床应用。在本研究中，提出了红曲色素（MP）纳米颗粒（PPM）来改善不良微环境并辅助骨髓来源的间充质干细胞（BMSCs）移植。同时，为了负载PPM并减少BMSCs的机械损伤，制备了基于席夫碱交联的可注射水凝胶。PPM具有清除ROS和调节巨噬细胞表型的能力，显著提高了BMSCs在HF微环境中的存活率和活性。这种水凝胶表现出优异的生物相容性、可注射性和组织粘附性。在可注射、粘性水凝胶和MP的微环境调节特性的协同作用下，大鼠心包囊内的心脏功能得到有效改善。我们的结果为推进基于BMSCs的HF治疗及其临床应用提供了见解。
