title: Adipose-Derived Stem Cells Improve Collagenase-Induced Tendinopathy in a Rat Model.
abstract: Tendinopathy is a common and highly prevalent musculoskeletal disorder characterized by repetitive activity-related pain and focal tendon tenderness. Histopathologically, tendinopathic tissue mainly shows degenerative changes. Therefore, tendinopathy is not affected by anti-inflammatory therapies. A novel approach, including a stem cell-based therapy, may be beneficial for its treatment.
  
  
  
  The purpose of this study was to evaluate the effects of adipose-derived stem cells (ASCs) on tendon healing in a rat tendinopathy model. The hypothesis was that ASC transplantation would improve degeneration in collagenase-induced tendinopathy.
  
  
  
  Controlled laboratory study.
  
  
  
  Sixteen F344/NSlc rats underwent collagenase injection into the Achilles tendon to induce tendinopathy. At 1 week after collagenase injection, 8 rats received ASCs (ASC group) and 8 received phosphate-buffered saline alone (PBS group). Animals were sacrificed at 4 or 12 weeks after ASC administration, and the degree of degeneration in each tendon was histologically evaluated according to the Bonar scale. The microstructure of healing tendons was observed by scanning electron microscopy. Reverse-transcription polymerase chain reaction (RT-PCR) was performed to measure the ratio of type III collagen messenger RNA (mRNA) to type I collagen mRNA in tendons.
  
  
  
  The median Bonar scale score in the ASC and PBS groups was 2.5 and 5.33 at 4 weeks after treatment and 1.0 and 4.0 at 12 weeks after treatment, respectively. Histologically, the ASC group showed a significantly lower degree of tendon degeneration than the PBS group at both time points. In the RT-PCR analysis, the ratio of type III collagen to type I collagen was significantly lower in the ASC group than in the PBS group at 12 weeks after treatment. Moreover, this ratio decreased over time in the ASC group, whereas it increased over time in the PBS group.
  
  
  
  The study findings demonstrate that the application of ASCs results in significant improvement in the pathological findings associated with tendinopathy and the normalization of collagen ratios within the affected tendon.
  
  
  
  Subcutaneous adipose tissue can be harvested easily, and ASC administration might have the potential to rapidly treat tendinopathy.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan Department of Orthopaedic Surgery, Japan Self Defense Force Hospital Yokosuka, Yokosuka, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Oshita
authors.affiliation: Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Morikuni
authors.initials: M
authors.lastname: Tobita
authors.affiliation: Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan Department of Dental Surgery, Japan Self Defense Force Hospital Yokosuka, Yokosuka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tajima
authors.affiliation: Department of Plastic and Reconstructive Surgery, Juntendo University School of Medicine, Tokyo, Japan hmizuno@juntendo.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuno
mesh_terms: D000125:Achilles Tendon / Q000378:metabolism / Q000473:pathology; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D017364:Collagenases / Q000009:adverse effects*; D004195:Disease Models, Animal; D006801:Humans; D051381:Rats; D011916:Rats, Inbred F344; D033581:Stem Cell Transplantation; D052256:Tendinopathy / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D017364:Collagenases
keywords: ASCs; collagen ratio; degeneration; tendinopathy