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Age-dependent decrease in the chondrogenic potential of human bone marrow mesenchymal stromal cells expanded with fibroblast growth factor-2
Authors:Masami Kanawa  Akira Igarashi  Veronica Sainik Ronald  Yukihito Higashi  Hidemi Kurihara  Masaru Sugiyama  Tania Saskianti  Haiou Pan  Yukio Kato
Institution:1. Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan;3. Department of Dental and Medical Biochemistry, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan;5. Department of Periodontal Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan;6. Department of Public Oral Health, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan;4. Research Center for Radiation Genome Medicine, Research Institute for Radiation Biology and Medicine, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan;2. Department of Advanced Technology and Development, BML, Inc, Saitama, Japan;7. Department of Pediatric Dentistry, Faculty of Dentistry, Airlangga University, Surabaya, Indonesia;8. Two Cells Inc, Hiroshima University, Hiroshima, Japan;3. Institute of Physical Chemistry, Karlsruhe Institute of Technology, D-76131 Karlsruhe, Germany;4. Institute of Biology, Experimental Biophysics, Humboldt-Universitaet zu Berlin, 10115 Berlin, Germany;5. Department of Bioengineering and Howard Hughes Medical Institute, Stanford University, Stanford, California 94305;1. Laboratory for Cell Biology, The First Affiliated Hospital, Zhengzhou University, 40 Daxue Road, Zhengzhou 450052, China;2. College of Life Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, China;3. Department of Oncology, The First Affiliated Hospital, Zhengzhou University, 1 East Jianshe Road, Zhengzhou 450052, China;1. Laboratory for Cell Biology, The First Affiliated Hospital, Zhengzhou University, Henan 450052, China;2. Henan Province Academician & Expert workstation, Clinical Research Centre, People''s Hospital of Zhengzhou, China;3. College of Bioengineering, Henan University of Technology, Henan 450001, China;4. Department of Biology, Zhengzhou University, Henan 450001, China
Abstract:Background aimsHuman bone marrow mesenchymal stromal cells are useful in regenerative medicine for various diseases, but it remains unclear whether the aging of donors alters the multipotency of these cells. In this study, we examined age-related changes in the chondrogenic, osteogenic and adipogenic potential of mesenchymal stromal cells from 17 donors (25–81 years old), including patients with or without systemic vascular diseases.MethodsAll stem cell lines were expanded with fibroblast growth factor-2 and then exposed to differentiation induction media. The chondrogenic potential was determined from the glycosaminoglycan content and the SOX9, collagen type 2 alpha 1 (COL2A1) and aggrecan (AGG) messenger RNA levels. The osteogenic potential was determined by monitoring the alkaline phosphatase activity and calcium content, and the adipogenic potential was determined from the glycerol-3-phosphate dehydrogenase activity and oil red O staining.ResultsSystemic vascular diseases, including arteriosclerosis obliterans and Buerger disease, did not significantly affect the trilineage differentiation potential of the cells. Under these conditions, all chondrocyte markers examined, including the SOX9 messenger RNA level, showed age-related decline, whereas none of the osteoblast or adipocyte markers showed age-dependent changes.ConclusionsThe aging of donors from young adult to elderly selectively decreased the chondrogenic potential of mesenchymal stromal cells. This information will be useful in stromal cell–based therapy for cartilage-related diseases.
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