title: Influence of the Injury-to-Surgery Interval on the Healing Potential of Human Anterior Cruciate Ligament-Derived Cells.
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.
  
  
  OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  During ACL reconstruction surgery, transplanting ACL remnant tissue in the early phase after injury could accelerate and enhance tendon-bone healing.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Inokuchi
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakano
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Shurong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Araki
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
mesh_terms: D000328:Adult; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000166:cytology* / Q000601:surgery; D059549:Anterior Cruciate Ligament Reconstruction / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D006801:Humans; D010012:Osteogenesis; D011923:Rats, Nude; D013710:Tendons / Q000637:transplantation; D013718:Tensile Strength; D013977:Tibia / Q000000981:diagnostic imaging / Q000502:physiology / Q000601:surgery; D013997:Time Factors; D014945:Wound Healing / Q000502:physiology*; D055114:X-Ray Microtomography
keywords: ACL reconstruction; CD34; angiogenesis; progenitor cells; surgical timing; tendon-bone healing