title: Effects of hypoxia on osteogenic differentiation of mesenchymal stromal cells used as a cell therapy for avascular necrosis of the femoral head.
abstract: Avascular necrosis of the femoral head (AVN) occurs as common result of various conditions or develops as a primary entity, with a high freqency in young adults. Because of its tendency toward osteoarthritis requiring total hip arthroplasty, alternative treatments are being advocated, including cell therapy with mesenchymal stromal cells (MSCs). Because osteonecrotic bone is a severely hypoxic tissue, with a 1-3% oxygen tension, the survival and function of multipotent cells is questionable.
  
  
  
  In this study, the proliferative, immunophenotypic and osteogenic properties of bone marrow (BM)-derived MSCs from a clinical series of patients with AVN were evaluated under in vitro conditions mimicking the hypoxic milieu of AVN to verify the rationale for cell therapy. MSCs retrieved from the iliac crest (BM-MSC) were isolated, expanded and induced to osteogenic differentiation under a 2% pO2 atmosphere (hypoxia) in comparison with the standard 21% pO2 (normoxia) that is routinely used in cell culture assays.
  
  
  
  Both proliferation and colony-forming ability were significantly enhanced in hypoxia-exposed BM-MSCs compared with BM-MSCs under normoxia. The expression of bone-related genes, including alkaline phosphatase, Type I collagen, and osteocalcin was significantly increased under hypoxia. Moreover, mineral deposition after osteogenic induction was not hampered, but in some cases even enhanced under low oxygen tension.
  
  
  
  These findings support autologous cell therapy as an effective treatment to stimulate bone healing in the hypoxic microenvironment of AVN.
authors.affiliation: Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address: gabriela.ciapetti@ior.it.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Ciapetti
authors.affiliation: Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: Granchi
authors.affiliation: Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Fotia
authors.affiliation: Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Savarino
authors.affiliation: Conservative Orthopaedic Surgery and Innovative Techniques, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Dante
authors.initials: D
authors.lastname: Dallari
authors.affiliation: Conservative Orthopaedic Surgery and Innovative Techniques, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Del Piccolo
authors.affiliation: 3rd Orthopaedic and Traumatologic Clinic, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.
authors.forename: Davide Maria
authors.initials: DM
authors.lastname: Donati
authors.affiliation: Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldini
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000235:genetics; D001854:Bone Marrow Cells / Q000166:cytology; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D049109:Cell Proliferation; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D005260:Female; D005271:Femur Head Necrosis / Q000473:pathology / Q000628:therapy*; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000166:cytology; D015675:Osteocalcin / Q000235:genetics; D010012:Osteogenesis
chemical_list: D024042:Collagen Type I; D015675:Osteocalcin; D000469:Alkaline Phosphatase
keywords: avascular necrosis; bone marrow stromal cells; bone regeneration; hypoxia