Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Physiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; and.
Hum Gene Ther. 2020 Mar;31(5-6):286-296. doi: 10.1089/hum.2019.306. Epub 2020 Mar 4.
Osteonecrosis of the femoral head (ONFH) is a common and disabling joint disease. Although there is no clear consensus on the complex pathogenic mechanism of ONFH, trauma, abuse of glucocorticoids, and alcoholism are implicated in its etiology. The therapeutic strategies are still limited, and the clinical outcomes are not satisfactory. Mesenchymal stem cells (MSCs) have been shown to exert a positive impact on ONFH in preclinical experiments and clinical trials. The beneficial properties of MSCs are due, at least in part, to their ability to home to the injured tissue, secretion of paracrine signaling molecules, and multipotentiality. Nevertheless, the regenerative capacity of transplanted cells is impaired by the hostile environment of necrotic tissue , limiting their clinical efficacy. Recently, genetic engineering has been introduced as an attractive strategy to improve the regenerative properties of MSCs in the treatment of early-stage ONFH. This review summarizes the function of several genes used in the engineering of MSCs for the treatment of ONFH. Further, current challenges and future perspectives of genetic manipulation of MSCs are discussed. The notion of genetically engineered MSCs functioning as a "factory" that can produce a significant amount of multipotent and patient-specific therapeutic product is emphasized.
股骨头坏死（ONFH）是一种常见且致残的关节疾病。尽管对于 ONFH 的复杂发病机制尚未达成明确共识，但创伤、滥用糖皮质激素和酗酒都与该病的病因有关。治疗策略仍然有限，临床疗效并不理想。在临床前实验和临床试验中，间充质干细胞（MSCs）已被证明对 ONFH 具有积极影响。MSCs 的有益特性至少部分归因于它们向损伤组织归巢、分泌旁分泌信号分子和多能性的能力。然而，移植细胞的再生能力受到坏死组织恶劣环境的限制，这限制了它们的临床疗效。最近，基因工程已被引入作为一种有吸引力的策略，以提高间充质干细胞在治疗早期 ONFH 中的再生特性。本综述总结了用于治疗 ONFH 的间充质干细胞工程中使用的几种基因的功能。此外，还讨论了基因修饰间充质干细胞的当前挑战和未来展望。强调了经过基因工程改造的间充质干细胞作为“工厂”的概念，该“工厂”可以产生大量多能且针对患者的治疗产品。
