PMID- 37922434 OWN - NLM STAT- MEDLINE DCOM- 20240129 LR - 20240206 IS - 2192-2659 (Electronic) IS - 2192-2640 (Linking) VI - 13 IP - 3 DP - 2024 Jan TI - Mesenchymal Stem Cell-Derived Mitochondria Enhance Extracellular Matrix-Derived Grafts for the Repair of Nerve Defect. PG - e2302128 LID - 10.1002/adhm.202302128 [doi] AB - Peripheral nerve injuries (PNI) can lead to mitochondrial dysfunction and energy depletion within the affected microenvironment. The objective is to investigate the potential of transplanting mitochondria to reshape the neural regeneration microenvironment. High-purity functional mitochondria with an intact structure are extracted from human umbilical cord-derived mesenchymal stem cells (hUCMSCs) using the Dounce homogenization combined with ultracentrifugation. Results show that when hUCMSC-derived mitochondria (hUCMSC-Mitos) are cocultured with Schwann cells (SCs), they promote the proliferation, migration, and respiratory capacity of SCs. Acellular nerve allografts (ANAs) have shown promise in nerve regeneration, however, their therapeutic effect is not satisfactory enough. The incorporation of hUCMSC-Mitos within ANAs has the potential to remodel the regenerative microenvironment. This approach demonstrates satisfactory outcomes in terms of tissue regeneration and functional recovery. Particularly, the use of metabolomics and bioenergetic profiling is used for the first time to analyze the energy metabolism microenvironment after PNI. This remodeling occurs through the enhancement of the tricarboxylic acid cycle and the regulation of associated metabolites, resulting in increased energy synthesis. Overall, the hUCMSC-Mito-loaded ANAs exhibit high functionality to promote nerve regeneration, providing a novel regenerative strategy based on improving energy metabolism for neural repair. CI - (c) 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH. FAU - Bai, Jun AU - Bai J AUID- ORCID: 0000-0003-3451-2090 AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Co-innovation Center of Neuroregeneration, Nantong University Nantong, Jiangsu Province, 226007, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Yu, Bingbing AU - Yu B AD - School of Materials Science and Engineering, The Key Laboratory of Advanced Materials of Ministry of Education, State Key Laboratory of New Ceramics and Fine Processing, Center for Flexible Electronics Technology, Tsinghua University, Beijing, 100084, P. R. China. FAU - Li, Chaochao AU - Li C AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Cheng, Haofeng AU - Cheng H AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. AD - School of Medicine, Nankai University, Tianjin, 300071, P. R. China. FAU - Guan, Yanjun AU - Guan Y AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Ren, Zhiqi AU - Ren Z AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Zhang, Tieyuan AU - Zhang T AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Song, Xiangyu AU - Song X AD - School of Medicine, Hebei North University, Zhangjiakou, 075051, P. R. China. FAU - Jia, Zhibo AU - Jia Z AD - School of Medicine, Hebei North University, Zhangjiakou, 075051, P. R. China. FAU - Su, Tianqi AU - Su T AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Tao, Benzhang AU - Tao B AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Gao, Haihao AU - Gao H AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Yang, Boyao AU - Yang B AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Liang, Lijing AU - Liang L AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Xiong, Xing AU - Xiong X AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Zhou, Xingyu AU - Zhou X AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. AD - Graduate School of Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Yin, Lan AU - Yin L AD - School of Materials Science and Engineering, The Key Laboratory of Advanced Materials of Ministry of Education, State Key Laboratory of New Ceramics and Fine Processing, Center for Flexible Electronics Technology, Tsinghua University, Beijing, 100084, P. R. China. FAU - Peng, Jiang AU - Peng J AUID- ORCID: 0000-0003-4662-9288 AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Co-innovation Center of Neuroregeneration, Nantong University Nantong, Jiangsu Province, 226007, P. R. China. FAU - Shang, Aijia AU - Shang A AD - Department of Neurosurgery, General Hospital of Chinese People Liberty Army, No. 28 Fuxing Road, Beijing, 100853, P. R. China. FAU - Wang, Yu AU - Wang Y AUID- ORCID: 0000-0001-7811-5834 AD - Institute of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital; Beijing Key Lab of Regenerative Medicine in Orthopedics, Key Laboratory of Musculoskeletal Trauma and War Injuries PLA, No. 51 Fucheng Road, Beijing, 100048, P. R. China. AD - Co-innovation Center of Neuroregeneration, Nantong University Nantong, Jiangsu Province, 226007, P. R. China. LA - eng GR - L222147/Beijing Natural Science Foundation/ GR - 32171356/National Natural Science Foundation of China/ GR - 2017YFA0104702/Key Technologies Research and Development Program/ PT - Journal Article DEP - 20231116 PL - Germany TA - Adv Healthc Mater JT - Advanced healthcare materials JID - 101581613 SB - IM MH - Humans MH - Sciatic Nerve MH - *Nerve Tissue MH - *Mesenchymal Stem Cells MH - Schwann Cells MH - *Peripheral Nerve Injuries/therapy MH - Extracellular Matrix MH - Nerve Regeneration/physiology OTO - NOTNLM OT - acellular nervous allograft OT - bioenergetics OT - mesenchymal stem cells OT - metabolism OT - mitochondrial transplantation OT - peripheral nerve regeneration EDAT- 2023/11/03 18:43 MHDA- 2024/01/29 06:43 CRDT- 2023/11/03 16:02 PHST- 2023/10/27 00:00 [revised] PHST- 2023/07/06 00:00 [received] PHST- 2024/01/29 06:43 [medline] PHST- 2023/11/03 18:43 [pubmed] PHST- 2023/11/03 16:02 [entrez] AID - 10.1002/adhm.202302128 [doi] PST - ppublish SO - Adv Healthc Mater. 2024 Jan;13(3):e2302128. doi: 10.1002/adhm.202302128. Epub 2023 Nov 16.