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损伤至手术间隔时间对人前交叉韧带来源细胞愈合潜能的影响。

Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament-Derived Cells.

作者信息

Inokuchi Takao, Matsumoto Tomoyuki, Takayama Koji, Nakano Naoki, Zhang Shurong, Araki Daisuke, Matsushita Takehiko, Kuroda Ryosuke

机构信息

Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.

出版信息

Am J Sports Med. 2017 May;45(6):1359-1369. doi: 10.1177/0363546517689871. Epub 2017 Mar 10.

DOI:10.1177/0363546517689871
PMID:28282242
Abstract

BACKGROUND

Vascular CD34+ cells in anterior cruciate ligament (ACL) tissue have the potential for high proliferation and multilineage differentiation that can accelerate tendon-bone healing. While patient characteristics, such as age, can affect tendon-bone healing, the influence of elapsed time after injury on the healing process is unclear.

HYPOTHESIS

Cells obtained during the early phase after injury will exhibit a greater tendon-bone healing potential compared with chronic phase counterparts when applied to an immunodeficient rat model of ACL reconstruction.

STUDY DESIGN

Controlled laboratory study.

METHODS

Adult human ACL-ruptured tissue was harvested from patients undergoing arthroscopic primary ACL reconstruction and classified into 2 groups based on the time elapsed between injury and surgery: (1) early group (≤3 months from injury) and (2) chronic group (>3 months from injury). In addition, 76 ten-week-old female immunodeficient rats underwent ACL reconstruction, followed by intracapsular administration of one of the following: (1) ACL-derived cells from the early group (n = 5), (2) ACL-derived cells from the chronic group (n = 5), or (3) phosphate-buffered saline (PBS) only (n = 5). During the 8 weeks after surgery, histological (weeks 2, 4, 8), immunohistochemical (week 2), radiographic (weeks 0, 2, 4, 8), and biomechanical (week 8) analyses were performed to evaluate tendon-bone healing.

RESULTS

In the early group, the histological evaluation showed early healing, induction of endochondral ossification-like integration, and mature bone ingrowth. Micro-computed tomography showed that the tibial bone tunnels at week 4 and week 8 were significantly reduced in the early group compared with those in the chronic group and PBS group ( P < .05). Moreover, biomechanical tensile strength was significantly greater in the early group than in the other groups ( P < .05). An accelerated healing potential in the early group was further demonstrated by the enhancement of intrinsic angiogenesis/osteogenesis and human-derived vasculogenesis/osteogenesis.

CONCLUSION

Compared with human ACL-derived cells obtained during the chronic phase, cells obtained during the early phase after injury have a greater tendon-bone healing potential when used in an immunodeficient rat model of ACL reconstruction.

CLINICAL RELEVANCE

During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone healing.

摘要

背景

前交叉韧带(ACL)组织中的血管CD34+细胞具有高增殖和多向分化潜能,可加速腱骨愈合。虽然患者特征(如年龄)会影响腱骨愈合,但损伤后时间对愈合过程的影响尚不清楚。

假设

当应用于免疫缺陷大鼠ACL重建模型时,与慢性期细胞相比,损伤后早期获得的细胞将表现出更大的腱骨愈合潜能。

研究设计

对照实验室研究。

方法

从接受关节镜下初次ACL重建的患者中获取成人ACL断裂组织,并根据损伤与手术之间的时间分为两组:(1)早期组(损伤后≤3个月)和(2)慢性组(损伤后>3个月)。此外,76只10周龄雌性免疫缺陷大鼠接受ACL重建,然后囊内给予以下之一:(1)早期组的ACL来源细胞(n = 5),(2)慢性组的ACL来源细胞(n = 5),或(3)仅磷酸盐缓冲盐水(PBS)(n = 5)。在术后8周内,进行组织学(第2、4、8周)、免疫组织化学(第2周)、影像学(第0、2、4、8周)和生物力学(第8周)分析以评估腱骨愈合。

结果

在早期组中,组织学评估显示早期愈合、诱导软骨内成骨样整合和成熟骨长入。微计算机断层扫描显示,与慢性组和PBS组相比,早期组在第4周和第8周时胫骨骨隧道明显减小(P <.05)。此外,早期组的生物力学拉伸强度明显高于其他组(P <.05)。早期组中固有血管生成/骨生成和人源性血管生成/骨生成的增强进一步证明了其加速愈合的潜能。

结论

与慢性期获得的人ACL来源细胞相比,损伤后早期获得的细胞在免疫缺陷大鼠ACL重建模型中使用时具有更大的腱骨愈合潜能。

临床意义

在ACL重建手术中,损伤后早期移植ACL残余组织可加速和增强腱骨愈合。

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