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The therapeutic effects of MSCs are increasingly attributed to immunomodulation, tissue repair and regeneration, paracrine effects, and mitochondrial transfer, rather than multilineage differentiation alone. Accumulating preclinical and clinical studies have demonstrated the therapeutic potential of MSCs across diverse disease settings, but clinical efficacy remains variable. However, differences in tissue source, donor age, expansion history, potency assays, and the disease microenvironment continue to limit reproducibility and clinical translation. Despite these advances, a comprehensive synthesis linking MSCs biology, mechanisms of action, disease\u2010specific evidence, and clinical translation is still lacking. This review summarizes the biological characteristics and heterogeneity of MSCs, and discusses the specific evidence and therapeutic mechanisms of MSCs in treating diseases such as musculoskeletal, cardiovascular, immune\u2010mediated, neurological, respiratory, and other diseases. We also summarize the major clinical transformation challenges of MSCs in treating various diseases. Additionally, we further explore emerging strategies to enhance the activity of MSCs, including pretreatment and activation, lifestyle intervention, and genetic engineering techniques. This review provides a comprehensive framework for developing safer, standardized, and clinically transformative therapies based on MSCs.<\/jats:p>","DOI":"10.1002\/mco2.70971","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T08:18:58Z","timestamp":1788855538000},"source":"Crossref","is-referenced-by-count":0,"title":["Applications of Mesenchymal Stromal Cells for Treatment of Diseases"],"prefix":"10.1002","volume":"7","author":[{"given":"Dongmei","family":"Xue","sequence":"first","affiliation":[{"name":"School of Medicine Chongqing University Cancer Hospital Chongqing University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2175-9449","authenticated-orcid":false,"given":"Yongsheng","family":"Li","sequence":"additional","affiliation":[{"name":"School of Medicine Chongqing University Cancer Hospital Chongqing University  Chongqing China"},{"name":"Department of Medical Oncology Chongqing University Cancer Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine Chongqing University Cancer Hospital Chongqing University  Chongqing China"},{"name":"Department of Medical Oncology Chongqing University Cancer Hospital  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/puh2.213"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26073084"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3016"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-025-02313-9"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.adw7107"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2024.12.037"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-024-00967-9"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s43556-025-00277-4"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2025.04.002"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231710023"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.115650"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.actbio.2021.03.069"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2024.1400347"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-01034-9"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176719"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-025-04699-3"},{"key":"e_1_2_15_18_1","first-page":"393","article-title":"The Development of Fibroblast Colonies in Monolayer Cultures of Guinea\u2010Pig Bone Marrow and Spleen Cells","volume":"3","author":"Friedenstein A. 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