Chen Liting, Huang Rongshan, Huang Chaoshuo, Nong Guiming, Mo Yuanyuan, Ye Lvyin, Lin Kunhong, Chen Anping
Department of Rheumatology and Immunology, Qinzhou First People's Hospital, Qinzhou, Guangxi, China.
Minda Hospital of Hubei Minzu University, Enshi, China.
Front Med (Lausanne). 2025 Jan 15;11:1530887. doi: 10.3389/fmed.2024.1530887. eCollection 2024.
Cell therapy is an emerging strategy for precision treatment of scleroderma. This review systematically summarizes the research progress of mesenchymal stem cell (MSC) and chimeric antigen receptor T cell (CAR-T) therapies in scleroderma and discusses the challenges and future directions for development. MSCs possess multiple functions, including immunomodulation, anti-fibrosis, and promotion of vascular regeneration, all of which can improve multiple pathological processes associated with scleroderma. Studies have demonstrated that MSCs can alleviate skin fibrosis by inhibiting CCL2 production and reducing the recruitment of pathological macrophages; their paracrine effects can exert extensive regulatory functions. CAR-T cell therapy ca specifically target and eliminate autoreactive immune cells, exhibiting enhanced specificity and personalized potential. Different cell therapies may have complementary and synergistic effects in treating scleroderma, such as MSCs exerting their effects through paracrine mechanisms while CAR-T cells specifically eliminate pathological cells. Furthermore, cell-free therapies derived from MSCs, such as extracellular vesicles or exosomes, may help circumvent the limitations of MSC therapy. Although cell therapy has opened new avenues for the precision treatment of scleroderma, it still faces numerous challenges. In the future, it is essential to strengthen integration of basic and clinical research, establish standardized protocols for cell preparation and quality control, develop personalized treatment plans, and rationally combine cell therapy with existing treatment methods to maximize its advantages and improve patient prognosis and quality of life.
细胞疗法是硬皮病精准治疗的一种新兴策略。本综述系统总结了间充质干细胞（MSC）和嵌合抗原受体T细胞（CAR-T）疗法在硬皮病治疗中的研究进展，并探讨了其面临的挑战和未来的发展方向。间充质干细胞具有多种功能，包括免疫调节、抗纤维化和促进血管再生，所有这些功能都可以改善与硬皮病相关的多种病理过程。研究表明，间充质干细胞可以通过抑制CCL2的产生和减少病理性巨噬细胞的募集来减轻皮肤纤维化；它们的旁分泌作用可以发挥广泛的调节功能。CAR-T细胞疗法可以特异性地靶向并清除自身反应性免疫细胞，具有更高的特异性和个性化潜力。不同的细胞疗法在治疗硬皮病时可能具有互补和协同作用，例如间充质干细胞通过旁分泌机制发挥作用，而CAR-T细胞则特异性地清除病理性细胞。此外，源自间充质干细胞的无细胞疗法，如细胞外囊泡或外泌体，可能有助于克服间充质干细胞疗法的局限性。尽管细胞疗法为硬皮病的精准治疗开辟了新途径，但仍面临诸多挑战。未来，必须加强基础研究与临床研究的整合，建立标准化的细胞制备和质量控制方案，制定个性化的治疗方案，并合理地将细胞疗法与现有治疗方法相结合，以最大限度地发挥其优势，改善患者的预后和生活质量。
