Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and osteogenesis in rabbit femoral head osteonecrosis |
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| Institution: | 1. Department of Orthopaedics and Rehabilitation, The Pennsylvania State University College of Medicine, Hershey, PA 17033, United States;2. Metabolic Disorders, Amgen Incorporated, Thousand Oaks, CA 91320, United States;3. BioServe Space Technologies, Department of Aerospace Engineering and Science, University of Colorado Boulder, CO 80309, United States;4. Department of Mechanical Engineering, University of Colorado Boulder, CO 80309, United States;5. Hewlett-Packard Labs Fort Collins, CO 80528, United States;6. Departments of Biomedical Engineering and Radiation Oncology, University of North Carolina, Chapel Hill, NC 27599, United States;1. Musculoskeletal Research Programme, University of Aberdeen, Aberdeen, UK;2. Department of Biomedical Engineering, University of Strathclyde, Glasgow, UK;3. Scottish Centre for Innovation in Spinal Cord Injury, Queen Elizabeth National Spinal Injuries Unit, Southern General Hospital, Glasgow, UK;1. Armed Forces Radiobiology Research Institute, Bethesda, MD 20889-5603, USA;2. Department of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA;3. Department of Radiation Biology, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA;4. Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, 20814 USA;5. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, 46202 USA;1. Department of Orthopaedic Surgery, Saint Louis University School of Medicine, 1402 S. Grand Blvd, Schwitalla Hall, M176, St. Louis, MO 63104, USA;2. Department of Orthopedic Surgery, Washington University in St. Louis School of Medicine, 660 S. Euclid, Campus Box8233, St. Louis, MO 63110, USA;1. Department of Biomedical Engineering, Eindhoven University of Technology, High Tech Campus 11-p1.243, 5656 AE Eindhoven, The Netherlands;2. Philips Research Europe, High Tech Campus 11-p1.261A, 5656 AE Eindhoven, The Netherlands;3. Department of Pathology, University Medical Center Utrecht, Room H04.312, Utrecht, The Netherlands |
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| Abstract: | PurposeOsteonecrosis of the femoral head may be a disease resulting from abnormal proliferation or differentiation of mesenchymal stem cells. The present investigation explored the novel strategy of hypoxia-preconditioned BMMSCs to reverse the impairment of osteonecrosis BMMSCs and enhance the therapeutic potential of hypoxia-treated BMMSC transplantation.MethodsBMMSCs from the anterior superior iliac spine region of osteonecrosis rabbit were cultured under 20% O2 or 2% O2 conditions. Normal BMMSCs were cultured under 20% O2 condition as control. Growth factors secreted were examined by enzyme-linked immunosorbent assay. 20% O2 or 2% O2 BMMSCs were injected into the femoral head of rabbits after core decompression. Cell viability and apoptosis were assessed in vitro, and TUNEL staining of the femoral head was analyzed after transplantation. Angiogenesis (capillary-like structure formation, CD31 immunohistochemical staining and ink infusion angiography) and osteogenesis (Alizarin red-S staining, micro-CT scanning and OCN immunohistochemical staining) tests were conducted as well.Results2% O2 exposure up-regulated growth factor secretion in BMMSCs. Apoptosis in 2% O2 group was lower when compared with that in 20% O2 osteonecrosis group. Cell viability in 2% O2 was significantly higher when compared with that in 20% O2 osteonecrosis group. Growth factor secretion, cell viability, apoptosis, capillary-like structure formation, Alizarin red-S staining, and ALP staining showed no difference between the 2% O2 BMMSC and normal BMMSC groups. Transplantation of 2% O2 versus 20% O2 mesenchymal stem cells after core decompression resulted in an increase in angiogenesis function and a decrease in local tissue apoptosis. Our study also found that osteogenesis function was improved after hypoxic stem cell transplantation.ConclusionHypoxic preconditioning of BMMSCs is an effective means of reversing the impairment of osteonecrosis BMMSCs, promoting their regenerative capability and therapeutic potential for the treatment of osteonecrosis. |
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