title: Stem cell therapy for bone repair: a systematic review and meta-analysis of preclinical studies with large animal models.
abstract: OBJECTIVE
  Injury to bone is a significant clinical challenge, due to its limited regenerative capacity. The current methods of repairing bone defect are surgical, highly invasive and not always successful. A systematic review and meta-analysis of preclinical studies involving large animals with bone defects were conducted to determine the treatment outcomes with stem cell therapies.
  
  
  METHODS
  A random effects meta-analysis of the available studies was conducted to assess the treatment outcomes including the rate of new bone formation and new bone mineral density (BMD). Stratified analyses were also conducted by separating studies based on each characteristic independently.
  
  
  RESULTS
  Pooled analysis of 20 preclinical studies showed a significant beneficial effect of stem cell therapy in increasing new bone formation (17.79%, 95% confidence interval [CI], 10.54, 25.03; P < 0.001) and BMD (276.94 mg cm(-2) , 95% CI, 62.71, 491.17; P < 0.001) for disease amelioration. Regarding new bone formation, a statistical improvement was similarly detected from randomized controlled trial groups (17.06%, 95% CI, 8.87, 25.24; P < 0.001) and cohort groups (17.43%, 95% CI, 10.79, 24.07; P < 0.001). Exploratory stratified analysis yielded significant predictors of new bone formation including cell number (<10(7) vs. ≥10(7) ; P = 0.048) and the route of cell delivery (combining with matrix scaffold showed more effect than direct cell injection, P = 0.041). The effect of stem cell therapy diminished after 12 weeks.
  
  
  CONCLUSIONS
  The study results suggest that stem cell therapy improves new bone formation and BMD in bone defect models. Future trials should focus on the transplantation of ≥10(7) stem cells, especially using slow release biodegradable scaffolds or repetitive cell injections.
authors.affiliation: Department of Clinical Pharmacy, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China; Department of Pharmacy, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Liao
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Zhang
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Fu-Ming
authors.initials: FM
authors.lastname: Shen
authors.forename: Ming-Kang
authors.initials: MK
authors.lastname: Zhong
mesh_terms: D000818:Animals; D015519:Bone Density; D059630:Mesenchymal Stem Cells / Q000502:physiology; D023421:Models, Animal; D010012:Osteogenesis; D017594:Publication Bias; D033581:Stem Cell Transplantation
keywords: animal model; bone defect; meta-analysis; stem cell therapy