title: Exploring the application of stem cells in tendon repair and regeneration.
abstract: OBJECTIVE
  To conduct a systematic review of the current evidence for the effects of stem cells on tendon healing in preclinical studies and human studies.
  
  
  METHODS
  A systematic search of the PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, and Embase databases was performed for stem cells and tendons with their associated terminology. Data validity was assessed, and data were collected on the outcomes of trials.
  
  
  RESULTS
  A total of 27 preclinical studies and 5 clinical studies met the inclusion criteria. Preclinical studies have shown that stem cells are able to survive and differentiate into tendon cells when placed into a new tendon environment, leading to regeneration and biomechanical benefit to the tendon. Studies have been reported showing that stem cell therapy can be enhanced by molecular signaling adjunct, mechanical stimulation of cells, and the use of augmentation delivery devices. Studies have also shown alternatives to the standard method of bone marrow-derived mesenchymal stem cell therapy. Of the 5 human studies, only 1 was a randomized controlled trial, which showed that skin-derived tendon cells had a greater clinical benefit than autologous plasma. One cohort study showed the benefit of stem cells in rotator cuff tears and another in lateral epicondylitis. Two of the human studies showed how stem cells were successfully extracted from the humerus and, when tagged with insulin, became tendon cells.
  
  
  CONCLUSIONS
  The current evidence shows that stem cells can have a positive effect on tendon healing. This is most likely because stem cells have regeneration potential, producing tissue that is similar to the preinjury state, but the results can be variable. The use of adjuncts such as molecular signaling, mechanical stimulation, and augmentation devices can potentially enhance stem cell therapy. Initial clinical trials are promising, with adjuncts for stem cell therapy in development.
authors.affiliation: Orthopaedic Research Unit, Addenbrooke's Hospital, Cambridge, England. zafar.ahmad@doctors.org.uk
authors.forename: Zafar
authors.initials: Z
authors.lastname: Ahmad
authors.forename: John
authors.initials: J
authors.lastname: Wardale
authors.forename: Roger
authors.initials: R
authors.lastname: Brooks
authors.forename: Fran
authors.initials: F
authors.lastname: Henson
authors.forename: Ali
authors.initials: A
authors.lastname: Noorani
authors.forename: Neil
authors.initials: N
authors.lastname: Rushton
mesh_terms: D001696:Biomechanical Phenomena; D016026:Bone Marrow Transplantation; D048091:Guided Tissue Regeneration / Q000379:methods*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D033581:Stem Cell Transplantation / Q000379:methods*; D013708:Tendon Injuries / Q000628:therapy*; D016896:Treatment Outcome; D014945:Wound Healing