title: Anterior cruciate ligament remnant tissue harvested within 3-months after injury predicts higher healing potential.
abstract: BACKGROUND
  No study has examined the possible factors associated with different characteristics of stem-like cells derived from anterior cruciate ligament (ACL) remnants. And the purpose of the study is to elucidate whether demographic factors are associated with healing potential of stem-like cells derived from the ACL remnants tissue.
  
  
  METHODS
  Thirty-six ACL remnants were harvested from patients who received primary arthroscopic ACL reconstruction. Interval from injury to surgery, age, sex, and combined meniscal or chondral injuries were analyzed. Cells were isolated from remnant tissues and their healing potential was evaluated by: 1) characterization of surface markers (CD34, CD44, CD45, CD146, CD29, and Stro-1), 2) cell expansion, 3) osteogenic differentiation, and 4) endothelial differentiation. Finally, using multivariable logistic regression to evaluate the relation between demographic factors and healing potential parameters. Adjusted odds ratios (OR) were calculated, and the significant difference was set at p < 0.05.
  
  
  RESULTS
  ACL remnant tissue harvested less than 90 days after injury predicted higher fractions of stem-like cells [CD34+ (OR = 6.043, p = 0.025), CD44 + (OR = 8.440, p = 0.011), CD45+ (OR = 16.144, p = 0.015), and CD146+ (OR = 9.246, p = 0.015)] and higher expansion potential (passage 3: OR = 9.755, p = 0.034; passage 10: OR = 33.245, p = 0.003). Regarding osteogenic differentiation, higher gene expression of Osteocalcin (OR = 22.579, p = 0.009), Alkaline phosphatase (OR = 6.527, p = 0.022), and Runt-related transcription factor 2 (OR = 5.247, p = 0.047) can also be predicted. Younger age predicted higher CD34+ levels (20 ≤ age < 30 years, OR = 2.020, p = 0.027) and higher expansion potential at passage 10 (10 ≤ age < 20 years, OR = 25.141, p = 0.026). There was no significant relation found between meniscal or chondral injuries and ACL healing potential.
  
  
  CONCLUSIONS
  Our results indicated that the ACL remnant tissue harvested within 3-months after injury yields higher healing potential, suggesting early surgical intervention may achieve better clinical results.
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. suyung1106@gmail.com.
authors.forename: Shurong
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, 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, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. auefuji@yahoo.co.jp.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Uefuji
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. matsushi@med.kobe-u.ac.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Matsushita
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. kojitakayama1978@gmail.com.
authors.forename: Koji
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. araki824@med.kobe-u.ac.jp.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Araki
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. naokix1981@yahoo.co.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakano
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. kant_kantona@yahoo.co.jp.
authors.forename: Kanto
authors.initials: K
authors.lastname: Nagai
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. tokiomatsuzaki@yahoo.co.jp.
authors.forename: Tokio
authors.initials: T
authors.lastname: Matsuzaki
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. kurodar@med.kobe-u.ac.jp.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kuroda
authors.affiliation: Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017, Japan. kurosaka@med.kobe-u.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
mesh_terms: D000293:Adolescent; D000328:Adult; D016118:Anterior Cruciate Ligament / Q000473:pathology* / Q000601:surgery; D000070598:Anterior Cruciate Ligament Injuries; D001182:Arthroscopy / Q000639:trends*; D002454:Cell Differentiation / Q000502:physiology; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D011237:Predictive Value of Tests; D013234:Stem Cells / Q000473:pathology / Q000502:physiology*; D013997:Time Factors; D061665:Time-to-Treatment / Q000639:trends*; D055815:Young Adult