Exp Mol Med.
2006 Jun;38(3):273-283.
Tissue engineering of heart valves by recellularization of glutaraldehyde-fixed porcine valves using bone marrow-derived cells
- Affiliations
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- 1Department of Bioengineering, Hanyang University, Seoul 133-791, Korea. bskim@hanyang.ac.kr
- 2Department of Pathology, Hanyang University, Seoul 133-791, Korea.
- 3Department of Chemical Engineering, Hanyang University, Seoul 133-791, Korea.
- 4Interdisciplinary Program for, Biochemical Engineering and Biotechnology, Korea.
- 5School of Chemical and Biological Engineering, Seoul National University, Seoul 151-742, Korea.
- 6Department of Thoracic and Cardiovascular Surgery, Ajou University School of Medicine, Suwon 443-749, Korea.
- 7Division of Cardiovascular Surgery, Yonsei Cardiovascular Center, College of Medicine Yonsei University, Seoul 120-752, Korea.
Abstract
- To increase the biocompatibility and durability of glutaraldehyde (GA)-fixed valves, a biological coating with viable endothelial cells (ECs) has been proposed. However, stable EC layers have not been formed successfully on GA-fixed valves due to their inability to repopulate. In this study, to improve cellular adhesion and proliferation, the GA-fixed prostheses were detoxified by treatment with citric acid to remove free aldehyde groups. Canine bone marrow mononuclear cells (MNCs) were differentiated into EC-like cells and myofibroblast-like cells in vitro. Detoxified prostheses were seeded and recellularized with differentiated bone marrow-derived cells (BMCs) for seven days. Untreated GA-fixed prostheses were used as controls. Cell attachment, proliferation, metabolic activity, and viability were investigated and cell-seeded leaflets were histologically analyzed. On detoxified GA-fixed prostheses, BMC seeding resulted in uninhibited cell proliferation after seven days. In contrast, on untreated GA-fixed prostheses, cell attachment was poor and no viable cells were observed. Positive staining for smooth muscle a-actin, CD31, and proliferating cell nuclear antigen was observed on the luminal side of the detoxified valve leaflets, indicating differentiation and proliferation of the seeded BMCs. These results demonstrate that the treatment of GA-fixed valves with citric acid established a surface more suitable for cellular attachment and proliferation. Engineering heart valves by seeding detoxified GA-fixed biological valve prostheses with BMCs may increase biocompatibility and durability of the prostheses. This method could be utilized as a new approach for the restoration of heart valve structure and function in the treatment of end-stage heart valve disease.
MeSH Terms
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Tissue Fixation
Tissue Engineering/*methods
Swine
Proliferating Cell Nuclear Antigen/analysis
Muscle, Smooth/chemistry
Microscopy, Electron, Scanning
Immunohistochemistry
Heart Valves/cytology/*physiology
Heart Valve Prosthesis
Glutaral/*chemistry
Endothelial Cells/cytology/physiology
Dogs
Cell Survival/physiology
Cell Proliferation
Cell Differentiation/physiology
Cell Culture Techniques/*methods
Cell Adhesion/physiology
Bone Marrow Cells/chemistry/*physiology/ultrastructure
Antigens, CD31/analysis
Animals
Actins/analysis
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