Lingchi Kong1,2, Yan Wang2, Haixing Wang2, Qi Pan2, Rongtai Zuo1, Shanshan Bai2, Xiaoting Zhang2, Wayne Yukwai Lee2, Qinglin Kang3, Gang Li4,5,6. 1. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd. 600, Shanghai, 200233, People's Republic of China. 2. Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR PRC. 3. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Yishan Rd. 600, Shanghai, 200233, People's Republic of China. orthokang@163.com. 4. Department of Orthopaedics & Traumatology, Stem Cells and Regenerative Medicine Laboratory, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR PRC. gangli@cuhk.edu.hk. 5. The CUHK-ACC Space Medicine Centre on Health Maintenance of Musculoskeletal System, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, People's Republic of China. gangli@cuhk.edu.hk. 6. Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR PRC. gangli@cuhk.edu.hk.
Abstract
BACKGROUND: Paracrine signaling from endothelial progenitor cells (EPCs) is beneficial for angiogenesis and thus promotes tissue regeneration. Microgravity (MG) environment is found to facilitate the functional potentials of various stem or progenitor cells. The present study aimed to elucidate the effects of MG on pro-angiogenic properties and fracture repair capacities of conditioned media (CM) from EPCs. METHODS: Human peripheral blood-derived EPCs were cultured under MG or normal gravity (NG) followed by analysis for angiogenic gene expression. Furthermore, the serum-free CM under MG (MG-CM) or NG (NG-CM) were collected, and their pro-angiogenic properties were examined in human umbilical vein endothelial cells (HUVECs). In order to investigate the effects of MG-CM on fracture healing, they were injected into the fracture gaps of rat models, and radiography, histology, and mechanical test were performed to evaluate neovascularization and fracture healing outcomes. RESULTS: MG upregulated the expression of hypoxia-induced factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) and promoted NO release. Comparing to NG-CM, MG-CM significantly facilitated the proliferation, migration, and angiogenesis of HUVECs through NO-induced activation of FAK/Erk1/2-MAPK signaling pathway. In addition, MG-CM were verified to improve angiogenic activities in fracture area in a rat tibial fracture model, accelerate fracture healing, and well restore the biomechanical properties of fracture bone superior to NG-CM. CONCLUSION: These findings provided insight into the use of MG bioreactor to enhance the angiogenic properties of EPCs' paracrine signals via HIF-1α/eNOS/NO axis, and the administration of MG-CM favored bone fracture repair.
BACKGROUND: Paracrine signaling from endothelial progenitor cells (EPCs) is beneficial for angiogenesis and thus promotes tissue regeneration. Microgravity (MG) environment is found to facilitate the functional potentials of various stem or progenitor cells. The present study aimed to elucidate the effects of MG on pro-angiogenic properties and fracture repair capacities of conditioned media (CM) from EPCs. METHODS:Human peripheral blood-derived EPCs were cultured under MG or normal gravity (NG) followed by analysis for angiogenic gene expression. Furthermore, the serum-free CM under MG (MG-CM) or NG (NG-CM) were collected, and their pro-angiogenic properties were examined in human umbilical vein endothelial cells (HUVECs). In order to investigate the effects of MG-CM on fracture healing, they were injected into the fracture gaps of rat models, and radiography, histology, and mechanical test were performed to evaluate neovascularization and fracture healing outcomes. RESULTS: MG upregulated the expression of hypoxia-induced factor-1α (HIF-1α) and endothelial nitric oxide synthase (eNOS) and promoted NO release. Comparing to NG-CM, MG-CM significantly facilitated the proliferation, migration, and angiogenesis of HUVECs through NO-induced activation of FAK/Erk1/2-MAPK signaling pathway. In addition, MG-CM were verified to improve angiogenic activities in fracture area in a rat tibial fracture model, accelerate fracture healing, and well restore the biomechanical properties of fracture bone superior to NG-CM. CONCLUSION: These findings provided insight into the use of MG bioreactor to enhance the angiogenic properties of EPCs' paracrine signals via HIF-1α/eNOS/NO axis, and the administration of MG-CM favored bone fracture repair.
Authors: T Asahara; T Murohara; A Sullivan; M Silver; R van der Zee; T Li; B Witzenbichler; G Schatteman; J M Isner Journal: Science Date: 1997-02-14 Impact factor: 47.728
Authors: Zhengmeng Yang; Lu Feng; Ming Wang; Yucong Li; Shanshan Bai; Xuan Lu; Haixing Wang; Xiaoting Zhang; Yaofeng Wang; Sien Lin; Micky D Tortorella; Gang Li Journal: Nutrients Date: 2022-05-18 Impact factor: 6.706
Authors: Ronni Baran; Shannon Marchal; Sebastian Garcia Campos; Emil Rehnberg; Kevin Tabury; Bjorn Baselet; Markus Wehland; Daniela Grimm; Sarah Baatout Journal: Biomedicines Date: 2021-12-28