Short- and long-term effects of olfactory ensheathing cells in the treatment of chronic spinal cord injury: a meta-analysis

doi:10.3969/j.issn.2095-4344.1595

Abstract

Abstract:

BACKGROUND: A number of clinical trials addressing olfactory ensheathing cells for the treatment of chronic spinal cord injury have been conducted in the world, but the efficacy and safety are still controversial.
OBJECTIVE: To evaluate the safety and efficacy of olfactory ensheathing cell transplantation for chronic spinal cord injury, and to further compare its short- and long-term efficacy.
METHODS: PubMed, Cochrane Library, EMBASE, CNKI and WanFang databases were searched at July 23, 2018 for retrieval of clinical trials addressing olfactory ensheathing cells in the treatment of chronic spinal cord injury. Types and cases of adverse events during the safety trial should be recorded in detail. In the enrolled studies, American Spinal Injury Association scale was used to assess the motor, light touch, and pinprick scores of spinal cord injury patients before and after cell transplantation. The follow-up time was recorded. Systematic evaluation of efficacy data was performed using Review Manager 5.3.
RESULTS AND CONCLUSION: Both short- and long-term follow-up data showed that the neurological function of patients was significantly improved after olfactory ensheathing cell transplantation (P < 0.05), and the results were homogeneous (I²< 50% and P > 0.1). However, the long-term efficacy was not as good as the short-term efficacy, which may be related to chronic rejection and olfactory ensheathing cell survival. The overall adverse event rate was 8.99%, and no complications associated with olfactory ensheathing cells occurred. These findings show that olfactory ensheathing cell transplantation is effective and safe in the treatment of chronic spinal cord injury, but it is still necessary to explore more minimally invasive approaches to reduce surgical complications. In addition, a large number of high-quality experiments and clinical trials are warranted to confirm factors affecting the long-term efficacy of olfactory ensheathing cell transplantation.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Spinal Cord Injuries, Cell Transplantation, Recovery of Function, Tissue Engineering

CLC Number:

R459.9

Chen Huijing, Chen Yun, Deng Yuer, Gan Yanling, Zhan Wengang, Tan Qijia, Xie Caijun, Li Cong, Zhang Zhiqiang. Short- and long-term effects of olfactory ensheathing cells in the treatment of chronic spinal cord injury: a meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2019, 23(9): 1468-1476.

Figures/Tables 5

2.3 Meta分析结果 2.3.1 疗效性分析 (1)短期疗效结果：异质性检验显示移植术后，短期运动及轻触觉功能改变在各研究间具有同质性(运动评分I2=0%，P=0.67；轻触觉评分I2=13%，P=0.31)，采用固定效应模型进行分析提示：脊髓损伤患者在嗅鞘细胞移植前后运动、轻触觉功能评分差异有显著性意义[WMD运动= 4.62，95% CI(3.22，6.01)，P < 0.000 01；WMD轻触觉=8.49，95%CI(6.76，10.22)，P < 0.000 01]，见图2，3。说明嗅鞘细胞移植后脊髓损伤患者的运动、轻触觉均有明显改善。针刺觉功能的亚组内各研究间具有中度异质性(I2= 52%，P=0.01)，见图4A。根据Cochrane手册，该研究不能接受I2 ≥ 50%的异质性结果。为确定短期针刺觉评分变化的异质性来源，对结果进行了敏感性分析：逐一删除单项研究结果再行Meta分析后发现，剔除Chen等[22]的研究后，异质性明显降低(I2=21%，P=0.23)。考虑该试验例数只有3例，明显小于其他研究，固将其剔除后采用固定效应模型进行分析：脊髓损伤患者在嗅鞘细胞移植前后针刺觉功能评分差异有显著性意义[WMD针刺觉=9.30，95%CI(7.58，11.02)，P < 0.000 01]，见图4B。说明嗅鞘细胞移植后脊髓损伤患者的针刺觉在短期内有明显改善。对嗅鞘细胞治疗晚期脊髓损伤的短期运动、轻触觉及针刺觉Meta分析结果绘制漏斗图，可见散点均匀分布在无效线两侧，提示发表偏倚的可能性很低，见图5。 (2)长期疗效结果：异质性检验显示移植术后，长期运动、轻触觉、针刺觉功能改变在各研究间具有同质性(运动评分I2=0%，P=0.95；轻触觉评分I2=0%，P=0.76；针刺觉评分I2=0%，P=0.91)，采用固定效应模型进行分析提示：脊髓损伤患者在嗅鞘细胞移植前后运动、轻触觉、针刺觉功能评分差异有显著性意义[WMD运动=3.53，95%CI (0.71，6.34)，P=0.01；WMD轻触觉=8.34，95%CI(4.65，12.03)，P < 0.000 01；WMD针刺觉=7.09，95%CI(3.27，10.91)，P < 0.000 3]，见图6。说明嗅鞘细胞移植后长期随访(≥1年)显示，脊髓损伤患者的运动、轻触觉及针刺觉均有明显改善。对嗅鞘细胞治疗晚期脊髓损伤的长期运动、轻触觉及针刺觉Meta分析结果绘制漏斗图，可见散点均匀分布在无效线两侧，提示发表偏倚的可能性很低，见图7。"

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