What Is the Optimal Timing of Transplantation of Neural Stem Cells in Spinal Cord Injury? A Systematic Review and Network Meta-Analysis Based on Animal Studies.

Zhizhong Shang,Baolin Zhang,Ruirui Wang,Pingping Wanyan,Xin Wang,Dongliang Li,Jinlei Chen,Mingchuan Wang

doi:10.3389/fimmu.2022.855309

Abstract

ObjectiveThe optimal transplantation timing of neural stem cells in spinal cord injury is fully explored in animal studies to reduce the risk of transformation to clinical practice and to provide valuable reference for future animal studies and clinical research.MethodSeven electronic databases, namely, PubMed, Web of Science, Embase, Wanfang, Chinese Scientific Journal Database (CSJD-VIP), China Biomedical Literature Database (CBM), and China National Knowledge Infrastructure (CNKI), were searched. The studies were retrieved from inception to November 2021. Two researchers independently screened the literature, extracted data, and evaluated the methodological quality based on the inclusion criteria.Results and DiscussionThirty-nine studies were incorporated into the final analyses. Based on the subgroup of animal models and transplantation dose, the results of network meta-analysis showed that the effect of transplantation in the subacute phase might be the best. However, the results of traditional meta-analysis were inconsistent. In the moderate-dose group of moderate spinal cord injury model and the low-dose group of severe spinal cord injury model, transplantation in the subacute phase did not significantly improve motor function. Given the lack of evidence for direct comparison between different transplantation phases, the indirectness of our network meta-analysis, and the low quality of evidence in current animal studies, our confidence in recommending cell transplantation in the subacute phase is limited. In the future, more high-quality, direct comparative studies are needed to explore this issue in depth.

Highlights

According to the Global Burden of Disease Study, the agestandardized incidence rates of spinal cord injury (SCI) is 13 cases (11–16 cases) per 100,000 people, which is equivalent to 27.04 million prevalent cases worldwide, and is on the rise [1]
The powerful therapeutic efficacy of stem cells must be demonstrated in animal models before starting a translational clinical trial, and issues such as the timings of transplantation and the risk of side effects should be addressed to reduce the risk of their transformation to clinical practice
In the traditional meta-analysis, through subgroup analysis of animal models and transplantation routes and doses, we found that the effects of high-dose cell transplantation in the subacute phase are significantly better than those of the negative control group both in the moderate injury model or the severe injury model

Summary

Introduction

According to the Global Burden of Disease Study, the agestandardized incidence rates of spinal cord injury (SCI) is 13 cases (11–16 cases) per 100,000 people, which is equivalent to 27.04 million prevalent cases worldwide, and is on the rise [1]. In addition to the loss of motor and sensory functions, patients with SCI will experience a series of serious consequences, such as neuropathic pain, spasticity, and dysfunction of bladder and rectal, causing great physical and mental suffering, while SCI and SCIrelated complications are difficult to recover [5]. Various treatments, such as anti-inflammatory medications (ketorolac, minocycline, riluzole, magnesium, etc.), decompression surgery, and good supportive management have been used clinically [6]. Therapy against SCI is still a major challenge, and recently, with the deepening research on the pathogenesis of SCI and the advances in regenerative medicine, stem cell transplantation may be an effective means to solve this problem

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