Gabriela Ciapetti1, Donatella Granchi2, Caterina Fotia2, Lucia Savarino2, Dante Dallari3, Nicola Del Piccolo3, Davide Maria Donati4, Nicola Baldini5. 1. Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy. Electronic address: gabriela.ciapetti@ior.it. 2. Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy. 3. Conservative Orthopaedic Surgery and Innovative Techniques, Istituto Ortopedico Rizzoli, Bologna, Italy. 4. 3rd Orthopaedic and Traumatologic Clinic, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy. 5. Orthopedic Pathophysiology and Regenerative Medicine Unit, Istituto Ortopedico Rizzoli, Bologna, Italy; Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.
Abstract
BACKGROUND AIMS: 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. METHODS: 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. RESULTS: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. CONCLUSIONS: These findings support autologous cell therapy as an effective treatment to stimulate bone healing in the hypoxic microenvironment of AVN.
RCT Entities:
BACKGROUND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These findings support autologous cell therapy as an effective treatment to stimulate bone healing in the hypoxic microenvironment of AVN.
Authors: Marta Camacho-Cardenosa; Alba Camacho-Cardenosa; Rafael Timón; Guillermo Olcina; Pablo Tomas-Carus; Javier Brazo-Sayavera Journal: Int J Environ Res Public Health Date: 2019-05-21 Impact factor: 3.390