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

• Published in: The American journal of sports medicine Vol. 45; no. 6; p. 1359
• Main Authors: Inokuchi, Takao, Matsumoto, Tomoyuki, Takayama, Koji, Nakano, Naoki, Zhang, Shurong, Araki, Daisuke, Matsushita, Takehiko, Kuroda, Ryosuke
• Format: Journal Article
• Language: English
• Published: United States 01.05.2017
• Subjects: Adult; Animals; Anterior Cruciate Ligament - cytology; Anterior Cruciate Ligament - surgery; Anterior Cruciate Ligament Reconstruction - methods; Cell Differentiation; Cell Proliferation; Female; Humans; Osteogenesis; Rats, Nude; Tendons - transplantation; Tensile Strength; Tibia - diagnostic imaging; Tibia - physiology; Tibia - surgery; Time Factors; Wound Healing - physiology; X-Ray Microtomography; progenitor cells; tendon-bone healing; ACL reconstruction; surgical timing; CD34; angiogenesis
• ISSN: 1552-3365
• DOI: 10.1177/0363546517689871

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