Conditioned media from endothelial progenitor cells cultured in simulated microgravity promote angiogenesis and bone fracture healing.

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.

• Authors: Lingchi Kong, Yan Wang, Haixing Wang, Qi Pan, Rongtai Zuo, Shanshan Bai, Xiaoting Zhang, Wayne Yukwai Lee, Qinglin Kang, Gang Li
• Journal: Stem cell research & therapy (Stem Cell Res Ther) Vol. 12 Issue 1 Pg. 47 (01 08 2021) ISSN: 1757-6512 [Electronic] England
• PMID: 33419467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned

Topics

• Animals
• Cells, Cultured
• Culture Media, Conditioned (pharmacology)
• Endothelial Progenitor Cells
• Fracture Healing
• Human Umbilical Vein Endothelial Cells
• Humans
• Neovascularization, Physiologic
• Rats
• Weightlessness