The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway

Xiaohui Wang; Chao Jiang; Yongyuan Zhang; Zhe Chen; Hong Fan; Yuyang Zhang; Zhiyuan Wang; Fang Tian; Jing Li; Hao Yang; Dingjun Hao

doi:10.1186/s13578-022-00765-y

The promoting effects of activated olfactory ensheathing cells on angiogenesis after spinal cord injury through the PI3K/Akt pathway

Cell Biosci. 2022 Mar 4;12(1):23. doi: 10.1186/s13578-022-00765-y.

Authors

Xiaohui Wang^#^{1

2}, Chao Jiang^#¹, Yongyuan Zhang¹, Zhe Chen¹, Hong Fan^{1

3}, Yuyang Zhang^{1

4}, Zhiyuan Wang¹, Fang Tian¹, Jing Li⁵, Hao Yang⁶, Dingjun Hao⁷

Affiliations

¹ Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
² Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, 61231, Bad Nauheim, Germany.
³ Department of Neurology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
⁴ Department of Medicine, Solna, Karolinska Institutet, 171 77, Stockholm, Sweden.
⁵ Department of Orthopaedic, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China.
⁶ Translational Medicine Center, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China. yanghao.71_99@yahoo.com.
⁷ Department of Spine Surgery, Hong Hui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China. haodingjun@mail.xjtu.edu.cn.

^# Contributed equally.

Abstract

Objective: The aim of this study was to investigate the pro-angiogenic potential of olfactory ensheathing cells (OECs) activated by curcumin (CCM) and lipopolysaccharide (LPS) and the possible underlying mechanisms.

Methods: Vascular endothelial cells or tissues were cultured and treated with conditioned medium (CM) extracted from activated OECs activated through the addition of LPS and CCM or unactivated controls. Concomitantly, the pro-angiogenic potential of OECs was assessed in vitro by aortic ring sprouting assay, endothelial wound healing assay, CCK-8 assay, and tube formation assay. Subsequently, the OECs were co-cultured with endothelial cells to evaluate their promoting effect on endothelial cell proliferation and migration following a mechanical scratch. Moreover, the spinal cord injury (SCI) model in rats was established, and the number of endothelial cells and vascular structure in the injured area after SCI was observed with OEC transplantation. Finally, the underlying mechanism was investigated by western blot analysis of phosphorylated kinase expression with or without the MK-2206 (Akt-inhibitor).

Result: The present results showed that the activated OECs can effectively promote vascular endothelial cells' proliferation, migration, and vessel-like structure formation. Strikingly, several pro-angiogenic growth factors such as VEGF-A and PDGF-AA, which facilitate vessel formation, were found to be significantly elevated in CM. In addition, the PI3K/Akt signaling pathway was found to be involved in pro-angiogenic events caused by activated OEC CM, displaying higher phosphorylation levels in cells. In contrast, the delivery of MK2206 can effectively abrogate all the positive effects.

Conclusions: OECs activated by LPS and CCM have a pro-angiogenic effect and can effectively promote angiogenesis and improve the microenvironment at the injury site when transplanted in the injured spinal cord. This potentiated ability of OECs to provide pro-angiogenic effects is likely mediated through the PI3K/Akt pathway.

Keywords: Angiogenesis; Cell transplantation; Endothelial cells; Olfactory ensheathing cells; PI3K/Akt; Spinal cord injury.

Abstract

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