Anterior cruciate ligament injury and stem cell therapy

doi:10.3969/j.issn.2095-4344.2017.21.023

Abstract

Abstract:

BACKGROUND: Anterior cruciate ligament (ACL) has been reported to hold a self-recovery potential, which may be related to certain cytokines and biological factors, such as stem cells or progenitor cells.
OBJECTIVE: To review the literatures about the relationship between mesenchymal stem cells and ACL injuries, and understand the potential of stem cells or progenitor cells differentiating into ACL, thus providing a basis for the clinical use of mesenchymal stem cells in the treatment of ACL injury.
METHODS: A computer-based online research of PubMed databases was performed to collect articles including reviews, clinical trials and basic studies using the English keywords of “ACL regeneration, stem/progenitor cells, mesenchymal stem cells”. Forty-five eligible articles were included finally.
RESULTS AND CONCLUSION: In recent years, there are a lot of studies addressing the treatment of ACL injuries and muscle/bone regeneration, but the use of stem cells is still far from the clinical requirements. The source of stem cells suitable for the ACL regeneration and their most suitable injection points are under discussion. Although the mesenchymal stem cells have been reported to successfully repair ACL injury in animal models, either trophic factors of stem cells or these cells themselves improving the regeneration remains unclear.

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: Stem Cells, Mesenchymal Stem Cells, Anterior Crucial Ligament, Cartilage, Tissue Engineering

CLC Number:

R318

Zhao Liang, Han Chang-xu, Ren Yi-zhong. Anterior cruciate ligament injury and stem cell therapy[J]. Chinese Journal of Tissue Engineering Research, 2017, 21(21): 3420-3425.

Figures/Tables 1

2.1 受损前交叉韧带的愈合及治疗 2.1.1 影响前交叉韧带愈合过程的因素肌腱和韧带的愈合过程发生缓慢，可分为3个阶段：①组织炎症期；②血管长入与细胞增生期；③韧带重建期。各阶段间无明显组织学与时间界限，约在第8周起，纤维瘢痕开始形成[4]。前交叉韧带再生的一个困难是其损伤或断裂后无法引起血小板聚集，从而不能激活凝血系统，因此难以自愈，这一点对第一阶段至关重要[5]。在受损前交叉韧带的愈合过程中，关节内环境发挥着至关重要的作用。因此，在韧带受损后，研究滑膜液的组成对分析影响韧带愈合的因素至关重要。在前交叉韧带断裂患者的滑膜液中，可以观察到基质金属蛋白酶3、白细胞介素6、组织金属蛋白酶抑制剂1的增多[6-7]。基质金属蛋白酶和组织金属蛋白酶抑制剂是组织重塑过程中重要的酶。基质金属蛋白酶/组织金属蛋白酶抑制剂比值较高的膝关节更易发生软骨破坏[6]。这种不平衡也可能会对前交叉韧带的愈合产生影响。Tang等[8]认为基质金属蛋白酶在关节内的积累是前交叉韧带修复减弱的原因。Higuchi等[6]的研究表明在前交叉韧带伤后的一段时间内，基质金属蛋白酶3浓度依然很高，然而组织金属蛋白酶抑制剂1浓度却下降。因此认为，前交叉韧带受伤后，治疗时机的选择可能对愈合产生一定影响。 2.1.2 前交叉韧带损伤的治疗目前前交叉韧带重建术的金标准是使用自体腘绳肌(半腱肌和股薄肌)或髌腱代替前交叉韧带。手术治疗特别适用于日常生活中膝盖承受高负荷运动的患者，尤其是经常做急停急起、快速变向的运动员患者。保守治疗包括矫形术、本体感觉训练，以及一些加强肌肉从而增加膝关节稳定性的训练。Lohmander等[9]在一项12年的随访中发现，在一组受伤的女性足球运动员中，其中82%患者的膝关节有骨性关节炎的影像学表现。成功地对受伤的运动员行前交叉韧带重建术，可以将创伤性骨关节炎进行有效的控制[10]。使用自体移植物重建前交叉韧带，存在来源限制、供区并发症等问题[11]。目前还没有由于移植物的差异而导致临床预后及稳定性差异的文献报道[12]。Frobell等[13]最近公布的一项前瞻性随机对照试验认为，经过5年随访研究，对于前交叉韧带断裂的患者，康复为主要治疗方式的非手术治疗与手术治疗相比，两者在膝关节损伤和骨关节炎的评分中治疗效果相当。此外，Costa-Paz等[14]发现前交叉韧带也有自愈的可能。他们回顾性分析了14例患者，均被建议手术，但因为种种原因未完成手术。这些患者均复查了MRI，显示断端有愈合以及轴移试验为阴性，这表明前交叉韧带存在自发愈合的可能性。2006年Steadman等[15]发表了促进骨骼未成熟运动员前交叉韧带损伤愈合的新方法。所谓的“愈合反应技术”(HRT)是前交叉韧带微裂隙旁的股骨，可在血液凝块的帮助下在促进前交叉韧带断端附着。他们还报导了此技术在一组超过40岁的全前交叉韧带断裂患者中是有效的[16]。前交叉韧带断裂不同治疗方法模式图见图2。"

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