title: Analysis of Cell Therapies Used in Clinical Trials for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review of the Literature.
abstract: Osteonecrosis of the femoral head (ONFH) is associated with regional loss of cells within bone, often resulting in pain and mechanical collapse. Our purpose was to analyze the cell-therapies used in clinical trials for the treatment of ONFH with regard to (1) cell-sources, (2) collection techniques, (3) cell-processing, (4) qualitative and quantitative characterizations, and (5) delivery methods.
  
  
  
  A systematic review of the current literature on the use of cell therapies for the treatment of ONFH was performed. Studies with a level-of-evidence III or higher were evaluated. A total of 1483 articles were screened. Eleven studies met the criteria to be included in this review.
  
  
  
  Ten studies used bone-marrow, and 1 study used blood as the cell-source. Nine studies used freshly isolated tissue-derived nucleated cells from bone-marrow, mixed bone marrow-derived nucleated cells, 1 study used mixed blood-derived nucleated cells, and 1 study used culture-expanded cells derived from bone marrow aspirate. Cell dose varied from 2-million to 3-billion cells. Qualitative cell characterization of injected cells using surface markers was done by 5 studies using CD34. Two studies assayed the cell-population using a colony-forming-unit assay.
  
  
  
  There is a lack of standardization with respect to the quantitative and qualitative characterization of methods for cell-harvest, cell-processing, and cell-transplantation/delivery. Cell-therapy holds promise as a means of restoring local cell populations that are made deficient because of injury or disease. However, the orthopedic community and patients will benefit greatly by a greater investment in blinded, randomized, controlled trials and clinical effectiveness trials that embrace rigorous standards.
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio; Instituto Universitario del Hospital Italiano de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Nicolas S
authors.initials: NS
authors.lastname: Piuzzi
authors.affiliation: Steadman Philippon Research Institute, Vail, Colorado.
authors.forename: Jorge
authors.initials: J
authors.lastname: Chahla
authors.affiliation: Department of Orthopaedic Surgery, University of Colorado Denver, Denver, Colorado.
authors.forename: Hao
authors.initials: H
authors.lastname: Jiandong
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Morad
authors.initials: M
authors.lastname: Chughtai
authors.affiliation: Steadman Philippon Research Institute, Vail, Colorado; Department of Orthopaedic Surgery, The Steadman Clinic, Vail, Colorado.
authors.forename: Robert F
authors.initials: RF
authors.lastname: LaPrade
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mont
authors.affiliation: Department of Orthopaedic Surgery and Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio.
authors.forename: George F
authors.initials: GF
authors.lastname: Muschler
authors.affiliation: Department of Orthopaedic Surgery, Washington University Orthopedics, St. Louis, Missouri.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Pascual-Garrido
mesh_terms: D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002986:Clinical Trials as Topic; D005270:Femur Head; D005271:Femur Head Necrosis / Q000628:therapy*; D006801:Humans; D014182:Transplantation, Autologous
keywords: avascular necrosis; cell-based therapy; hip; osteonecrosis; osteonecrosis of femoral head; stem cells