Partially brain effects of injection of human umbilical cord mesenchymal stem cells at injury sites in a mouse model of thoracic spinal cord contusion

Haijun Hu; Houqing Long; Zhenxiao Ren; Tianhua Liu; Jinghui Xu; Fan Xiao

doi:10.3389/fnmol.2023.1179175

Partially brain effects of injection of human umbilical cord mesenchymal stem cells at injury sites in a mouse model of thoracic spinal cord contusion

Front Mol Neurosci. 2023 Jun 5:16:1179175. doi: 10.3389/fnmol.2023.1179175. eCollection 2023.

Authors

Haijun Hu^#¹, Houqing Long^#², Zhenxiao Ren^#^{2

3}, Tianhua Liu⁴, Jinghui Xu³, Fan Xiao¹

Affiliations

¹ Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
² Department of Spine Surgery, Orthopaedic, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University/The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, China.
³ Guangdong Provincial Key Laboratory of Orthopaedics and Traumatology/Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
⁴ Department of Oncology, Guangzhou Modern Hospital, Guangzhou, Guangdong, China.

^# Contributed equally.

Abstract

Purpose: The pain caused by spinal cord injury (SCI) poses a major burden on patients, and pain management is becoming a focus of treatment. Few reports have described changes in the brain after SCI. Particularly, the exact mechanism through which brain regions affect post-injury pain remains unclear. In this study, we aimed to determine the potential therapeutic mechanisms of pain. A mouse model of spinal cord contusion was established, and molecular expression in the anterior cingulate cortex (ACC) and periaqueductal gray (PAG) in the brain and animal behavior was observed after local injection of human umbilical cord mesenchymal stem cells (HU-MSCs) at the site of SCI.

Method: Sixty-three female C57BL/6J mice were divided into four groups: a sham operation group (n = 15); a spinal injury group (SCI, n = 16); an SCI + HU-MSCs group (n = 16) and an SCI + PBS group (n = 16), in which the SCI site was injected with HU-MSCs/phosphate buffer. The BMS score was determined, and the von Frey test and Hargreaves test were used to assess behavior every week after surgery. Mice were sacrificed in the fourth week after operation, and samples were collected. The expression of CGRP, Substance P, C-Fos and KCC2 in the ACC and PAG were observed with immunohistochemistry. Chromic cyanine staining was used to observe transverse sections of the injured spinal cord.

Result: In the ACC and PAG after SCI, the expression of CGRP, SP and C-Fos increased, and the expression of KCC2 decreased, whereas after HU-MSC injection, the expression of CGRP, SP and C-Fos decreased, and the expression of KCC2 increased. The SCI + HU-MSC group showed better exercise ability from 2 to 4 weeks after surgery than the SCI/SCI + PBS groups (P < 0.001). Local injection of HU-MSCs significantly improved the mechanical hyperalgesia caused by SCI in the fourth week after surgery (P < 0.0001), and sensation was significantly recovered 2 weeks after surgery (P < 0.0001); no improvement in thermal hypersensitivity was observed (P > 0.05). The HU-MSC group retained more white matter than the SCI/SCI + PBS groups (P < 0.0001).

Conclusion: Local transplantation of HU-MSCs at the site of SCI partially relieves the neuropathic pain and promotes recovery of motor function. These findings suggest a feasible direction for the future treatment of SCI.

Keywords: anterior cingulate cortex (ACC); contusion; human umbilical cord mesenchymal stem cells (hu-MSCs); neurogenic pain; periaqueductal gray (PAG); spinal cord injury (SCI).

Grants and funding

This study was supported by grants from the Project of the Jiangxi Provincial Department of Science and Technology (No. 20171BAB215017) and the Project of Jiangxi Provincial Department of Education (No. 2017GJJ170032).