Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model
IntroductionThe clinical translation of mesenchymal stem cell-derived exosome faces critical challenges in scalable production, subpopulation stability, and therapeutic route optimization. This study systematically addresses these barriers to advance exosome-based therapies.MethodsWe established a 2...
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2025.1550447/full |
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| author | Lina Zhang Jing Jin Jing Jin Liguang Sun Gang Hou Mingming Deng Yiding Bian Jianming Liu Wei Cheng Shaoliang Xing Shaoliang Xing Wenjia Wang Xin Dong Qingjie Fan Lei Gao Xinhua Lei Xinhua Lei Yongli Bao Yongguang Yang |
| author_facet | Lina Zhang Jing Jin Jing Jin Liguang Sun Gang Hou Mingming Deng Yiding Bian Jianming Liu Wei Cheng Shaoliang Xing Shaoliang Xing Wenjia Wang Xin Dong Qingjie Fan Lei Gao Xinhua Lei Xinhua Lei Yongli Bao Yongguang Yang |
| author_sort | Lina Zhang |
| collection | DOAJ |
| description | IntroductionThe clinical translation of mesenchymal stem cell-derived exosome faces critical challenges in scalable production, subpopulation stability, and therapeutic route optimization. This study systematically addresses these barriers to advance exosome-based therapies.MethodsWe established a 28-day biomanufacturing workflow using a Hollow Fiber 3D bioreactor integrated with the RoosterBio exosome-harvesting system. Exosomes were subsequently purified and rigorously characterized at multiple production stages, followed by isotopically labeled with 89Zr for biodistribution studies. Therapeutic efficacy was evaluated in a silica-induced mouse silicosis model comparing intravenous and respiratory administration routes.ResultsOur findings indicate that (1) the RoosterBio exosome harvesting system in the Hollow Fiber 3D bioreactor enables 28 days production of exosomes, with stable harvesting of the main subpopulations over a certain period; (2) systemic administration via intravenous injection in rats reveals distinct tissue tropism, with isotope-labeled exosomes exhibiting predominant hepatic accumulation; and (3) in the silica-induced mouse silicosis model, respiratory delivery of exosomes significantly improves disease progression, whereas intravenous infusion of exosomes does not yield notable therapeutic effects.DiscussionThis study proposes a holistic workflow for early-stage development of natural exosomes as therapeutics, offering guidance on industrial-scale production, purification, and characterization of exosomes with stable subpopulation distribution and functional consistency. It further addresses administration route selection in pulmonary disease animal models and heterogeneity assessment of natural exosomes. These advancements facilitate clinical translation of exosome-based therapies. |
| format | Article |
| id | doaj-art-7d273a7bc6db41ea923a0aca5ee5eacf |
| institution | OA Journals |
| issn | 2296-634X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj-art-7d273a7bc6db41ea923a0aca5ee5eacf2025-08-20T02:29:12ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2025-05-011310.3389/fcell.2025.15504471550447Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse modelLina Zhang0Jing Jin1Jing Jin2Liguang Sun3Gang Hou4Mingming Deng5Yiding Bian6Jianming Liu7Wei Cheng8Shaoliang Xing9Shaoliang Xing10Wenjia Wang11Xin Dong12Qingjie Fan13Lei Gao14Xinhua Lei15Xinhua Lei16Yongli Bao17Yongguang Yang18School of Life Sciences, Northeast Normal University, Changchun, Jilin, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, The First Hospital of Jilin University, Changchun, Jilin, ChinaResearch and Development Department (R&D), Beijing Jizhongke Biotechnology Co., LTD., Beijing, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, The First Hospital of Jilin University, Changchun, Jilin, ChinaDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, ChinaDepartment of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, ChinaResearch and Development Department (R&D), Beijing Jizhongke Biotechnology Co., LTD., Beijing, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, The First Hospital of Jilin University, Changchun, Jilin, ChinaResearch and Development Department (R&D), Jilin Zhong Ke Bio-engineering Co., LTD., Changchun, Jilin, ChinaResearch and Development Department (R&D), Jilin Zhong Ke Bio-engineering Co., LTD., Changchun, Jilin, ChinaResearch and Development Department (R&D), Jilin Zhong Ke Bio-engineering Co., LTD., Changchun, Jilin, ChinaResearch and Development Department (R&D), Beijing Jizhongke Biotechnology Co., LTD., Beijing, ChinaResearch and Development Department (R&D), Beijing Jizhongke Biotechnology Co., LTD., Beijing, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, The First Hospital of Jilin University, Changchun, Jilin, ChinaResearch and Development Department (R&D), Beijing Jizhongke Biotechnology Co., LTD., Beijing, ChinaSchool of Life Sciences, Northeast Normal University, Changchun, Jilin, ChinaNational-Local Joint Engineering Laboratory of Animal Models for Human Disease, The First Hospital of Jilin University, Changchun, Jilin, ChinaIntroductionThe clinical translation of mesenchymal stem cell-derived exosome faces critical challenges in scalable production, subpopulation stability, and therapeutic route optimization. This study systematically addresses these barriers to advance exosome-based therapies.MethodsWe established a 28-day biomanufacturing workflow using a Hollow Fiber 3D bioreactor integrated with the RoosterBio exosome-harvesting system. Exosomes were subsequently purified and rigorously characterized at multiple production stages, followed by isotopically labeled with 89Zr for biodistribution studies. Therapeutic efficacy was evaluated in a silica-induced mouse silicosis model comparing intravenous and respiratory administration routes.ResultsOur findings indicate that (1) the RoosterBio exosome harvesting system in the Hollow Fiber 3D bioreactor enables 28 days production of exosomes, with stable harvesting of the main subpopulations over a certain period; (2) systemic administration via intravenous injection in rats reveals distinct tissue tropism, with isotope-labeled exosomes exhibiting predominant hepatic accumulation; and (3) in the silica-induced mouse silicosis model, respiratory delivery of exosomes significantly improves disease progression, whereas intravenous infusion of exosomes does not yield notable therapeutic effects.DiscussionThis study proposes a holistic workflow for early-stage development of natural exosomes as therapeutics, offering guidance on industrial-scale production, purification, and characterization of exosomes with stable subpopulation distribution and functional consistency. It further addresses administration route selection in pulmonary disease animal models and heterogeneity assessment of natural exosomes. These advancements facilitate clinical translation of exosome-based therapies.https://www.frontiersin.org/articles/10.3389/fcell.2025.1550447/fullmesenchymal stem cells exosomesexosome subpopulation heterogeneityscalable productionbiomanufacturing workflownatural exosome therapy |
| spellingShingle | Lina Zhang Jing Jin Jing Jin Liguang Sun Gang Hou Mingming Deng Yiding Bian Jianming Liu Wei Cheng Shaoliang Xing Shaoliang Xing Wenjia Wang Xin Dong Qingjie Fan Lei Gao Xinhua Lei Xinhua Lei Yongli Bao Yongguang Yang Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model Frontiers in Cell and Developmental Biology mesenchymal stem cells exosomes exosome subpopulation heterogeneity scalable production biomanufacturing workflow natural exosome therapy |
| title | Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model |
| title_full | Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model |
| title_fullStr | Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model |
| title_full_unstemmed | Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model |
| title_short | Mesenchymal stem cell-derived exosome subpopulations remained consistent for 28 culture days, displaying therapeutic effects in a silicosis mouse model |
| title_sort | mesenchymal stem cell derived exosome subpopulations remained consistent for 28 culture days displaying therapeutic effects in a silicosis mouse model |
| topic | mesenchymal stem cells exosomes exosome subpopulation heterogeneity scalable production biomanufacturing workflow natural exosome therapy |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2025.1550447/full |
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