title: Stem cell injections in knee osteoarthritis: a systematic review of the literature.
abstract: OBJECTIVE
  Stem cell injection for knee osteoarthritis (KOA) is an emerging new therapy, and we aimed to review its evidence of efficacy.
  
  
  METHODS
  Systematic review.
  
  
  METHODS
  Criteria for eligibility were randomised controlled trials (RCTs) and non-RCT on the efficacy of stem cell injections in KOA. All references were checked for missed articles.
  
  
  METHODS
  MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Library, PEDro and SPORTDiscus were searched. A grey literature search was performed. No restrictions were imposed to our search strategy.
  Risk of bias was assessed using the Cochrane risk of bias tool. Descriptive synthesis was performed using the levels of evidence according to the Oxford Levels of Evidence.
  
  
  RESULTS
  Five RCTs and one non-RCT were found. Bone-marrow-derived stem cells, adipose-derived mesenchymal stem cells and peripheral blood stem cells were used. All trials were at high risk of bias, resulting in level-3 evidence. All five RCTs reported superior efficacy for patient-reported outcomes (Visual Analogue Scale, Western Ontario and McMaster Universities Arthritis Index, Tegner, Lysolm, International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Lequesne) compared with controls at final follow-up (range 24-48 months). Superior radiological outcomes were found favouring stem cell injection. Superior histological outcomes and/or improved arthroscopically scored healing rates were reported in two trials. No serious adverse events were reported.
  
  
  CONCLUSIONS
  Six trials with high risk of bias showed level-3 or level-4 evidence in favour of stem cell injections in KOA. In the absence of high-level evidence, we do not recommend stem cell therapy for KOA.
authors.affiliation: Department of Sports Medicine, The Sports Physicians Group, OLVG West, Amsterdam, The Netherlands.|Department of Orthopaedic Surgery, Academic Medical Centre, Amsterdam, The Netherlands.|Amsterdam Center of Evidence Based Sports Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Haiko Imfl
authors.initials: HI
authors.lastname: Pas
authors.affiliation: Rehabilitation and Sports Medicine Department, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Marinus
authors.initials: M
authors.lastname: Winters
authors.affiliation: Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, Groningen University, Groningen, The Netherlands.
authors.forename: Hidde J
authors.initials: HJ
authors.lastname: Haisma
authors.affiliation: Department of Rehabilitation Medicine, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Martinus Jj
authors.initials: MJ
authors.lastname: Koenis
authors.affiliation: Department of Sports Medicine, The Sports Physicians Group, OLVG West, Amsterdam, The Netherlands.|Amsterdam Center of Evidence Based Sports Medicine, Academic Medical Center, Amsterdam, The Netherlands.|Aspetar, Orthopedic and Sports Medicine Hospital, Doha, Qatar.
authors.forename: Johannes L
authors.initials: JL
authors.lastname: Tol
authors.affiliation: Department of Sports Medicine, The Sports Physicians Group, OLVG West, Amsterdam, The Netherlands.|Department of Sports Medicine, Bergman Clinics, Naarden, The Netherlands.|Department of Elite Sports, National Olympic Committee - Netherlands Sports Federation, Arnhem, The Netherlands.
authors.forename: Maarten H
authors.initials: MH
authors.lastname: Moen
mesh_terms: D015982:Bias; D006801:Humans; D007270:Injections, Intra-Articular; D020370:Osteoarthritis, Knee / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology
keywords: Cellular; Knee; Osteoarthritis