title: Age-dependent healing potential of anterior cruciate ligament remnant-derived cells.
abstract: BACKGROUND
  The anterior cruciate ligament (ACL) does not heal spontaneously after injury, and ACL patients of different ages respond differently to treatment. Although ACL-derived CD34-positive cells contribute to bone-tendon healing after ACL reconstruction, the relationship between the healing potential of ACL-derived cells and a patient's age is unknown.
  
  
  OBJECTIVE
  ACL-derived cells from young patients will have a greater effect on the maturation of bone-tendon integration in an immunodeficient rat model of ACL reconstruction compared with cells derived from older patients.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Sixty 10-week-old female immunodeficient rats underwent ACL reconstruction (using the autologous flexor digitorum longus tendon as a graft) followed by intracapsular administration of ACL-derived cells from patients aged 10 to 19 years (younger group) or patients aged 30 to 39 years (older group), or they were given phosphate-buffered saline (PBS; PBS group). Histologic, radiographic, and biomechanical examinations were performed 2 to 8 weeks after surgery. In addition, intrinsic and human cell-derived angiogenesis and osteogenesis were examined by immunohistochemistry.
  
  
  RESULTS
  In the younger group, histologic assessment demonstrated early bone-tendon healing, which induced endochondral ossification-like integration. Micro-computed tomography showed a statistically significant reduction in the area of tibial bone tunnel in the younger group (week 4, 20.0% ± 11.2% reduction; week 8, 25.7% ± 5.6% reduction) compared with the older group (week 4, 1.8% ± 3.0% reduction; week 8, 4.0% ± 5.9% reduction) and the PBS group (week 4, -0.5% ± 3.2% reduction; week 8, 3.3% ± 5.2% reduction) (week 4, P < .05; week 8, P < .01). Failure loads during tensile testing demonstrated a significantly higher ultimate load to failure in the younger group (17.52 ± 4.01 N) compared with the older (8.05 ± 2.91 N) and PBS (7.01 ± 3.16 N) groups (P < .05), and isolectin B4 and rat osteocalcin immunostaining indicated enhanced intrinsic angiogenesis and osteogenesis in the younger group. There was no statistically significant difference in the results of radiographic and biomechanical examinations between the older and PBS groups. Double immunohistochemistry for human-specific endothelial cell and osteoblast markers demonstrated a greater ability of differentiation into endothelial cells and osteoblasts in the younger group.
  
  
  CONCLUSIONS
  ACL-derived cells from younger patients enhanced early bone-tendon healing in an immunodeficient rat model of ACL reconstruction.
  
  
  CONCLUSIONS
  Surgeons should consider a patient's age when performing ACL reconstruction with remnant preservation or ruptured tissue incorporation, as this can predict healing ability.
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 matsun@m4.dion.ne.jp.
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: Takehiko
authors.initials: T
authors.lastname: Matsushita
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: Atsuo
authors.initials: A
authors.lastname: Uefuji
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kanto
authors.initials: K
authors.lastname: Nagai
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: Takao
authors.initials: T
authors.lastname: Inokuchi
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Nishida
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D016118:Anterior Cruciate Ligament / Q000166:cytology* / Q000000981:diagnostic imaging / Q000502:physiology*; D059549:Anterior Cruciate Ligament Reconstruction; D002454:Cell Differentiation; D002648:Child; D003239:Connective Tissue Cells / Q000737:chemistry; D042783:Endothelial Cells / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D037102:Lectins / Q000032:analysis; D008297:Male; D018919:Neovascularization, Physiologic; D010006:Osteoblasts / Q000502:physiology; D015675:Osteocalcin / Q000032:analysis; D010012:Osteogenesis; D051381:Rats; D013710:Tendons / Q000502:physiology* / Q000637:transplantation; D013718:Tensile Strength; D013977:Tibia / Q000000981:diagnostic imaging / Q000601:surgery; D053675:Versicans; D014945:Wound Healing; D055114:X-Ray Microtomography; D055815:Young Adult
chemical_list: D006023:Glycoproteins; D037102:Lectins; C508324:Vcan protein, rat; D015675:Osteocalcin; D053675:Versicans
keywords: ACL reconstruction; age-related differences; angiogenesis; bone-tendon healing; osteogenesis