Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament-Derived Cells
Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament-Derived Cells
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DOI：
10.1177/0363546517689871
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发表时间：
2017-05-01
影响因子：
4.8
通讯作者：
Kuroda, Ryosuke
中科院分区：
文献类型：
--
作者：
Inokuchi, Takao;Matsumoto, Tomoyuki;Kuroda, Ryosuke
背景资料：前交叉韧带（ACL）组织中的血管CD 34+细胞具有高度增殖和多向分化的潜力，可以加速肌腱-骨愈合。虽然患者的特征，如年龄，可以影响肌腱-骨愈合，但损伤后经过的时间对愈合过程的影响尚不清楚。假设：当应用于ACL重建的免疫缺陷大鼠模型时，与慢性期对应物相比，损伤后早期获得的细胞将表现出更大的肌腱-骨愈合潜力。研究设计：对照实验室研究。从接受关节镜下初次ACL重建的患者中收获成人ACL破裂组织，并基于损伤和手术之间的时间分为2组：（1）早期组（损伤后3个月）和（2）慢性组（损伤后>3个月）。此外，对76只10周龄雌性免疫缺陷大鼠进行ACL重建，然后囊内施用以下之一：（1）来自早期组的ACL衍生细胞（n = 5），（2）来自慢性组的ACL衍生细胞（n = 5），或（3）仅磷酸盐缓冲盐水（PBS）（n = 5）。术后8周行组织学（第2、4、8周）、免疫组化（第2周）、影像学（第0、2、4、8周）和生物力学（第8周）分析以评价腱-骨愈合。微电脑断层扫描显示，早期组第4周和第8周胫骨隧道较慢性组和PBS组明显缩小（P <0.05）。此外，早期组的生物力学拉伸强度显著高于其他组（P <0.05）。通过增强内在血管生成/成骨和人源性血管生成/成骨进一步证明了早期组的加速愈合潜力。结论：与慢性期获得的人ACL衍生细胞相比，损伤后早期获得的细胞在用于免疫缺陷大鼠ACL重建模型时具有更大的肌腱-骨愈合潜力。在ACL重建手术中，损伤后早期移植ACL残端组织可加速和促进腱骨愈合。
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.