title: The effect of tendon stem/progenitor cell (TSC) sheet on the early tendon healing in a rat Achilles tendon injury model.
abstract: Tissue-engineering approaches have a great potential to improve the treatment of tendon injuries that affect millions of people. The present study tested the hypothesis that introduction of a tendon derived stem/progenitor cell (TSC) sheet accelerates tendon healing and tendon regeneration in a rat model. TSC sheets were produced on temperature-responsive culture dishes. Then, they were grafted on unwounded Achilles tendons and at sites of a 3mm of Achilles tendon defect. At 2 and 4weeks after implantation tendons were examined by histology, immunohistochemistry, transmission electron microscopy (TEM) and mechanical testing. The results showed that the implanted TSC sheet remained stably attached on the tendon surface at 4 weeks after implantation. Moreover, in the tendon defect model, tendon defect area where TSC sheet was implanted was well regenerated and had better organized collagen fibers with elongated spindle shaped cells, compared to relatively disorganized collagen fibers and round shaped cells in the control group. TEM observations revealed longitudinally aligned collagen fibers and thick collagen fibrils in the TSC sheet implanted group. Finally, at 4weeks mechanical property of the TSC sheet implanted tendon had better ultimate load than the control. In conclusion, this study demonstrates the feasibility of implanting TSC sheets on tendons in vivo. Introduction of the cell sheets into a tendon defect significantly improved histological properties and collagen content at both 2 and 4 weeks after implantation, indicating that TSC sheets may effectively promote tendon remodeling in the early stages of tendon healing.
  
  
  
  Tendon injury is a highly prevalent clinical problem that debilitates millions of people worldwide in both occupational and athletic settings. It also costs billions of healthcare dollars in treatment every year. In this study, we showed the feasibility of using tendon derived stem cell sheet to deliver biologically active tenogenic-constructs and promote tendon regeneration. This work has the potential to impact the orthopaedic surgery and sports medicine fields in the treatment of tendon injury.
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada, Shinjuku, Tokyo 162-8480, Japan; MechanoBioblogy Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, Pittsburgh, PA 15213, United States.
authors.forename: Issei
authors.initials: I
authors.lastname: Komatsu
authors.affiliation: MechanoBioblogy Laboratory, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 210 Lothrop Street, Pittsburgh, PA 15213, United States.
authors.forename: James H-C
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Cooperative Major in Advanced Biomedical Sciences, Faculty of Science and Engineering, Waseda University, 2-2 Wakamatsucho, Shinjuku, Tokyo 162-8480, Japan.
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Iwasaki
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada, Shinjuku, Tokyo 162-8480, Japan. Electronic address: shimizu.tatsuya@twmu.ac.jp.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada, Shinjuku, Tokyo 162-8480, Japan.
authors.forename: Teruo
authors.initials: T
authors.lastname: Okano
mesh_terms: D000125:Achilles Tendon / Q000473:pathology* / Q000648:ultrastructure; D000818:Animals; D001696:Biomechanical Phenomena; D002469:Cell Separation; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020007:Implants, Experimental; D008297:Male; D051381:Rats; D015203:Reproducibility of Results; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology*; D013708:Tendon Injuries / Q000473:pathology* / Q000628:therapy*
keywords: Cell sheet; Tendon derived stem/progenitor cells (TSCs); Tendon regeneration