Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects
Autologous nerve transplantation (ANT) remains the gold standard for treating nerve defects. However, its efficacy in nerve repair still requires improvement. Mitochondrial dysfunction resulting from nerve injury may be a significant factor limiting nerve function restoration. This study investigate...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2024-10-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.1177/09636897241291278 |
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| author | Dongdong Li Haolin Liu Chaochao Li Yanjun Guan Xing Xiong Ruichao He Zhibo Jia Lijing Liang Jinjuan Zhao Xinyu Miao Yu Wang Jiang Peng |
| author_facet | Dongdong Li Haolin Liu Chaochao Li Yanjun Guan Xing Xiong Ruichao He Zhibo Jia Lijing Liang Jinjuan Zhao Xinyu Miao Yu Wang Jiang Peng |
| author_sort | Dongdong Li |
| collection | DOAJ |
| description | Autologous nerve transplantation (ANT) remains the gold standard for treating nerve defects. However, its efficacy in nerve repair still requires improvement. Mitochondrial dysfunction resulting from nerve injury may be a significant factor limiting nerve function restoration. This study investigated the impact of supplementing exogenous mitochondria (EM) in ANT and explored its effect on the efficacy of ANT in nerve repair. SD rats were used to prepare a model of a 10 mm sciatic nerve defect repaired by ANT (Auto group) and a model of ANT supplemented with EM (Mito group). At 12 weeks post-operation, functional, neurophysiological, and histological evaluations of the target organ revealed that the Mito group exhibited significantly better outcomes compared with the Auto group, with statistically significant differences ( P < 0.05). In vitro experiments demonstrated that EM could be endocytosed by Schwann cells (SCs) and dorsal root ganglion neurons (DRGs) when co-cultured. After endocytosis by SCs, immunofluorescence staining of autophagy marker LC3II and mitochondrial marker Tomm20, as well as adenoviral fluorescence labeling of lysosomes and mitochondria, revealed that EM could promote autophagy in SCs. CCK8 and EDU assays also indicated that EM significantly promoted SCs proliferation and viability. After endocytosis by DRGs, EM could accelerate axonal growth rate. A sciatic nerve defect repair model prepared using Thy1-YFP-16 mice also revealed that EM could accelerate axonal growth in vivo , with statistically significant results ( P < 0.05). This study suggests that EM enhances autophagy in SCs, promotes SCs proliferation and viability, and increases the axonal growth rate, thereby improving the efficacy of ANT. This research provides a novel therapeutic strategy for enhancing the efficacy of ANT in nerve repair. |
| format | Article |
| id | doaj-art-cfa7dc50cfc449fea88fe0a47b961137 |
| institution | Kabale University |
| issn | 1555-3892 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj-art-cfa7dc50cfc449fea88fe0a47b9611372025-08-20T03:34:13ZengSAGE PublishingCell Transplantation1555-38922024-10-013310.1177/09636897241291278Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve DefectsDongdong Li0Haolin Liu1Chaochao Li2Yanjun Guan3Xing Xiong4Ruichao He5Zhibo Jia6Lijing Liang7Jinjuan Zhao8Xinyu Miao9Yu Wang10Jiang Peng11Department of Orthopedics, The Ninth Medical Center of Chinese PLA General Hospital, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaCo-innovation Center of Neuroregeneration, Nantong University, Nantong, ChinaInstitute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital, Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma & War Injuries PLA, Beijing, ChinaAutologous nerve transplantation (ANT) remains the gold standard for treating nerve defects. However, its efficacy in nerve repair still requires improvement. Mitochondrial dysfunction resulting from nerve injury may be a significant factor limiting nerve function restoration. This study investigated the impact of supplementing exogenous mitochondria (EM) in ANT and explored its effect on the efficacy of ANT in nerve repair. SD rats were used to prepare a model of a 10 mm sciatic nerve defect repaired by ANT (Auto group) and a model of ANT supplemented with EM (Mito group). At 12 weeks post-operation, functional, neurophysiological, and histological evaluations of the target organ revealed that the Mito group exhibited significantly better outcomes compared with the Auto group, with statistically significant differences ( P < 0.05). In vitro experiments demonstrated that EM could be endocytosed by Schwann cells (SCs) and dorsal root ganglion neurons (DRGs) when co-cultured. After endocytosis by SCs, immunofluorescence staining of autophagy marker LC3II and mitochondrial marker Tomm20, as well as adenoviral fluorescence labeling of lysosomes and mitochondria, revealed that EM could promote autophagy in SCs. CCK8 and EDU assays also indicated that EM significantly promoted SCs proliferation and viability. After endocytosis by DRGs, EM could accelerate axonal growth rate. A sciatic nerve defect repair model prepared using Thy1-YFP-16 mice also revealed that EM could accelerate axonal growth in vivo , with statistically significant results ( P < 0.05). This study suggests that EM enhances autophagy in SCs, promotes SCs proliferation and viability, and increases the axonal growth rate, thereby improving the efficacy of ANT. This research provides a novel therapeutic strategy for enhancing the efficacy of ANT in nerve repair.https://doi.org/10.1177/09636897241291278 |
| spellingShingle | Dongdong Li Haolin Liu Chaochao Li Yanjun Guan Xing Xiong Ruichao He Zhibo Jia Lijing Liang Jinjuan Zhao Xinyu Miao Yu Wang Jiang Peng Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects Cell Transplantation |
| title | Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects |
| title_full | Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects |
| title_fullStr | Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects |
| title_full_unstemmed | Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects |
| title_short | Exogenous Mitochondrial Transplantation Facilitates the Recovery of Autologous Nerve Grafting in Repairing Nerve Defects |
| title_sort | exogenous mitochondrial transplantation facilitates the recovery of autologous nerve grafting in repairing nerve defects |
| url | https://doi.org/10.1177/09636897241291278 |
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