Mitochondria Transplantation to Bone Marrow Stromal Cells Promotes Angiogenesis During Bone Repair

Author:

Wang Yifan1,Li Wenjing2,Guo Yusi2,Huang Ying2,Guo Yaru2,Song Jia2,Mei Feng3,Liao Peiwen4,Gong Zijian2,Chi Xiaopei2,Deng Xuliang2ORCID

Affiliation:

1. National Engineering Laboratory for Digital and Material Technology of Stomatology NMPA Key Laboratory for Dental Materials & Beijing Laboratory of Biomedical Materials Department of Geriatric Dentistry Peking University School and Hospital of Stomatology Beijing 100081 P. R. China

2. National Engineering Laboratory for Digital and Material Technology of Stomatology NMPA Key Laboratory for Dental Materials & Beijing Laboratory of Biomedical Materials Department of Geriatric Dentistry Peking University School and Hospital of Stomatology People's Republic of China. Peking University Health Science Center and Hospital of Stomatology Beijing 100081 P. R. China

3. Department of Stomatology Union Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430022 P. R. China

4. Peking University Health Science Center and Hospital of Stomatology Beijing 100081 P. R. China

Abstract

AbstractAngiogenesis is crucial for successful bone defect repair. Co‐transplanting Bone Marrow Stromal Cells (BMSCs) and Endothelial Cells (ECs) has shown promise for vascular augmentation, but it face challenges in hostile tissue microenvironments, including poor cell survival and limited efficacy. In this study, the mitochondria of human BMSCs are isolated and transplanted to BMSCs from the same batch and passage number (BMSCsmito). The transplanted mitochondria significantly boosted the ability of BMSCsmito‐ECs to promote angiogenesis, as assessed by in vitro tube formation and spheroid sprouting assays, as well as in vivo transplantation experiments in balb/c mouse and SD rat models. The Dll4‐Notch1 signaling pathway is found to play a key role in BMSCsmito‐induced endothelial tube formation. Co‐transplanting BMSCsmito with ECs in a rat cranial bone defect significantly improves functional vascular network formation, and improve bone repair outcomes. These findings thus highlight that mitochondrial transplantation, by acting through the DLL4‐Notch1 signaling pathway, represents a promising therapeutic strategy for enhancing angiogenesis and improving bone repair. Hence, mitochondrial transplantation to BMSCS as a therapeutic approach for promoting angiogenesis offers valuable insights and holds much promise for innovative regenerative medicine therapies.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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