Romero-García Nekane, Mas-Bargues Cristina, Huete-Acevedo Javier, Borrás Consuelo
Freshage Research Group, Department of Physiology, Faculty of Medicine, University of Valencia, Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable-Instituto de Salud Carlos III (CIBERFES-ISCIII), INCLIVA, Valencia, Spain.
Subcell Biochem. 2023;102:271-311. doi: 10.1007/978-3-031-21410-3_11.
Ageing is a complex process characterized by deteriorated performance at multiple levels, starting from cellular dysfunction to organ degeneration. Stem cell-based therapies aim to administrate stem cells that eventually migrate to the injured site to replenish the damaged tissue and recover tissue functionality. Stem cells can be easily obtained and cultured in vitro, and display several qualities such as self-renewal, differentiation, and immunomodulation that make them suitable candidates for stem cell-based therapies. Current animal studies and clinical trials are being performed to assess the safety and beneficial effects of stem cell engraftments for regenerative medicine in ageing and age-related diseases.Since alterations in cell-cell communication have been associated with the development of pathophysiological processes, new research is focusing on the modulation of the microenvironment. Recent research has highlighted the important role of some microenvironment components that modulate cell-cell communication, thus spreading signals from damaged ageing cells to neighbor healthy cells, thereby promoting systemic ageing. Extracellular vesicles (EVs) are small-rounded vesicles released by almost every cell type. EVs cargo includes several bioactive molecules, such as lipids, proteins, and genetic material. Once internalized by target cells, their specific cargo can induce epigenetic modifications and alter the fate of the recipient cells. Also, EV's content is dependent on the releasing cells, thus, EVs can be used as biomarkers for several diseases. Moreover, EVs have been proposed to be used as cell-free therapies that focus on their administration to slow or even reverse some hallmarks of physiological ageing. It is not surprising that EVs are also under study as next-generation therapies for age-related diseases.
衰老过程复杂，其特征是从细胞功能障碍到器官退化的多个层面上性能恶化。基于干细胞的疗法旨在施用干细胞，这些干细胞最终迁移到损伤部位以补充受损组织并恢复组织功能。干细胞易于在体外获取和培养，并具有自我更新、分化和免疫调节等多种特性，使其成为基于干细胞疗法的合适候选者。目前正在进行动物研究和临床试验，以评估干细胞移植在衰老及与年龄相关疾病的再生医学中的安全性和有益效果。
由于细胞间通讯的改变与病理生理过程的发展有关，新的研究聚焦于微环境的调节。最近的研究强调了一些调节细胞间通讯的微环境成分的重要作用，这些成分将信号从受损的衰老细胞传播到相邻的健康细胞，从而促进全身衰老。细胞外囊泡（EVs）是几乎每种细胞类型释放的小圆形囊泡。EVs的货物包括多种生物活性分子，如脂质、蛋白质和遗传物质。一旦被靶细胞内化，其特定货物可诱导表观遗传修饰并改变受体细胞的命运。此外，EVs的内容物取决于释放细胞，因此，EVs可作为多种疾病的生物标志物。此外，有人提议将EVs用作无细胞疗法，重点是通过施用它们来减缓甚至逆转生理衰老的一些特征。EVs作为与年龄相关疾病的下一代疗法正在研究中也就不足为奇了。
