title: Transplantation of tendon-derived stem cells pre-treated with connective tissue growth factor and ascorbic acid in vitro promoted better tendon repair in a patellar tendon window injury rat model.
abstract: OBJECTIVE
  Treatment of tendon-derived stem cells (TDSCs) with connective tissue growth factor (CTGF) and ascorbic acid promoted their tenogenic differentiation. We investigated the effects of TDSCs pre-treated with CTGF and ascorbic acid on tendon repair in a patellar tendon window injury rat model.
  
  
  METHODS
  Green fluorescent protein-TDSCs (GFP-TDSCs) were pre-treated with or without CTGF and ascorbic acid for 2 weeks before transplantation. The patellar tendons of rats were injured and divided into three groups: fibrin glue-only group (control group), untreated and treated TDSC group. The rats were followed up until week 16.
  
  
  RESULTS
  The treated TDSCs accelerated and enhanced the quality of tendon repair compared with untreated TDSCs up to week 8, which was better than that in the controls up to week 16 as shown by histology, ultrasound imaging and biomechanical test. The fibrils in the treated TDSC group showed better alignment and larger size compared with those in the control group at week 8 (P = 0.004). There was lower risk of ectopic mineralization after transplantation of treated or untreated TDSCs (all P ≤ 0.050). The transplanted cells proliferated and could be detected in the window wound up to weeks 2 to 4 and week 8 for the untreated and treated TDSC groups, respectively.
  
  
  CONCLUSIONS
  The transplantation of TDSCs promoted tendon repair up to week 16, with CTGF and ascorbic acid pre-treatment showing the best results up to week 8. Pre-treatment of TDSCs with CTGF and ascorbic acid may be used to further enhance the rate and quality of tendon repair after injury.
authors.affiliation: Headquarter, Hospital Authority, Hong Kong SAR, China. Electronic address: paulinelui00@gmail.com.
authors.forename: Pauline Po Yee
authors.initials: PP
authors.lastname: Lui
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: On Tik
authors.initials: OT
authors.lastname: Wong
authors.affiliation: Department of Orthopaedics and Traumatology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Yuk Wa
authors.initials: YW
authors.lastname: Lee
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D001696:Biomechanical Phenomena / Q000187:drug effects; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation; D055513:Connective Tissue Growth Factor / Q000494:pharmacology*; D004195:Disease Models, Animal; D024022:Fibrillar Collagens / Q000378:metabolism / Q000648:ultrastructure; D015718:Fibrin Tissue Adhesive / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D017847:Patellar Ligament / Q000293:injuries; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013708:Tendon Injuries / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D013710:Tendons / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D014057:Tomography, X-Ray Computed; D014463:Ultrasonography; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D024022:Fibrillar Collagens; D015718:Fibrin Tissue Adhesive; D018809:Proliferating Cell Nuclear Antigen; D055513:Connective Tissue Growth Factor; D049452:Green Fluorescent Proteins; D001205:Ascorbic Acid
keywords: connective tissue growth factor (CTGF) and ascorbic acid; tendon healing; tendon repair; tendon stem/progenitor cells; tendon tissue engineering; tendon-derived stem cells (TDSCs)