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World J Stem Cells. Jul 26, 2026; 18(7): 119895
Published online Jul 26, 2026. doi: 10.4252/wjsc.119895
Platelet-derived mitochondria transfer accelerates fracture healing by promoting osteogenic differentiation and metabolic reprogramming of adipose-derived stem cells
Zhu Pan, Rui Zhang, Gai-Mei Du, Ji-Hai Yi, Jin Bao, Cai-Dong Liu
Zhu Pan, Department of Sports Medicine and Joint Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing 210006, Jiangsu Province, China
Rui Zhang, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210006, Jiangsu Province, China
Gai-Mei Du, Department of Animal Science and Food Engineering, Jinling Technology Institution, Nanjing 210006, Jiangsu Province, China
Ji-Hai Yi, College of Animal Science and Technology, Shihezi University, Shihezi 832003, Xinjiang Uygur Autonomous Region, China
Jin Bao, Cai-Dong Liu, Department of Blood Transfusion, Nanjing First Hospital, Nanjing 210006, Jiangsu Province, China
Cai-Dong Liu, School of Medicine, Shihezi University, Shihezi 832061, Xinjiang Uygur Autonomous Region, China
Co-first authors: Zhu Pan and Rui Zhang.
Co-corresponding authors: Jin Bao and Cai-Dong Liu.
Author contributions: Bao J and Liu CD designed and coordinated the study, they contributed equally to this manuscript and are co-corresponding authors; Pan Z and Zhang R performed the experiments, acquired and analyzed data, and wrote the manuscript, they contributed equally to this manuscript and are co-first authors; Du GM and Yi JH interpreted the data; and all authors approved the final version of the article.
AI contribution statement: Portions of this manuscript were edited using AI tools for language refinement. The authors were responsible and agree to accountability for all scientific content.
Supported by 2024 Jiangsu Blood Transfusion Association Research Fund, No. JSYK2024005.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of Nanjing First Hospital (Approval No. DWSY-25080712).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Cai-Dong Liu, Department of Blood Transfusion, Nanjing First Hospital, No. 68 Changle Road, Qinhuai District, Nanjing 210006, Jiangsu Province, China.
liucd2281@163.com
Received: February 10, 2026
Revised: April 11, 2026
Accepted: June 4, 2026
Published online: July 26, 2026
Processing time: 165 Days and 8 Hours
BACKGROUND
Platelets promote fracture repair by transferring mitochondria to recipient cells. Adipose-derived stem cells (ASCs) have garnered significant attention in bone regeneration due to their osteogenic differentiation potential.
AIM
To investigate the effect of platelet-derived mitochondria on ASC osteogenesis and elucidate the underlying molecular mechanism.
METHODS
ASCs were isolated from Sprague-Dawley rats and characterized. ASCs were treated with platelets isolated from rat whole blood or platelet-derived mitochondria, and then evaluated for glycolysis and osteogenic differentiation. Histone lactylation and its impact on gene transcription were analyzed. A rat closed femoral fracture model was established to evaluate mitochondrial roles in vivo.
RESULTS
Platelets enhanced glycolysis and osteogenic differentiation of ASCs. Platelet-derived mitochondria exhibit a similar pro-osteogenic and metabolic effect, and these mitochondria were found to be internalized by ASCs. Mitochondria induced H3K18 lactylation, which enriched the promoters of AXIN2, BMPR1B, COL1A1, and OSTN, thereby promoting their transcription. 2-deoxy-D-glucose treatment or H3K18R transfection reversed the mitochondrial-induced enhancement of glycolysis and osteogenesis. Additionally, platelet-derived mitochondria amplified ASC-mediated fracture repair, an effect counteracted by 2-deoxy-D-glucose.
CONCLUSION
Platelet-derived mitochondrial transfer promotes osteogenic gene transcription via H3K18 lactylation, facilitating osteogenic differentiation and accelerating fracture healing. This study reveals a novel metabolic-epigenetic mechanism in fracture repair.
Core Tip: Platelets promote glycolysis and osteogenic differentiation of adipose-derived stem cells (ASCs) by transferring mitochondria. Mechanically, mitochondria facilitate H3K18 lactylation, thereby inducing transcription of AXIN2, BMPR1B, COL1A1, and OSTN. Moreover, platelet-derived mitochondria enhance the effect of ASCs on fracture healing through glycolysis. Collectively, platelet-derived mitochondria transfer promotes the lactylation of H3K18 through lactate produced by glycolysis, promotes the transcription of osteogenesis-related genes, thereby promoting the osteogenic differentiation of ASCs and then accelerating fracture healing.
