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Tissue engineering of heart valves by recellularization of glutaraldehyde-fixed porcine valves using bone marrow-derived cells.

Authors
Kim, SS; Lim, SH; Cho, SW; Gwak, SJ; Hong, YS; Chang, BC; Park, MH; Song, KW; Choi, CY; Kim, BS
Citation
Experimental & molecular medicine, 38(3):273-283, 2006
Journal Title
Experimental & molecular medicine
ISSN
1226-36132092-6413
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
Actins/analysisAnimalsAntigens, CD31/analysisBone Marrow Cells/chemistryBone Marrow Cells/physiology*Bone Marrow Cells/ultrastructureCell Adhesion/physiologyCell Culture Techniques/methods*Cell Differentiation/physiologyCell ProliferationCell Survival/physiologyDogsEndothelial Cells/cytologyEndothelial Cells/physiologyGlutaral/chemistry*Heart Valve ProsthesisHeart Valves/cytologyHeart Valves/physiology*ImmunohistochemistryMicroscopy, Electron, ScanningMuscle, Smooth/chemistryProliferating Cell Nuclear Antigen/analysisSwineTissue Engineering/methods*Tissue Fixation
DOI
10.1038/emm.2006.33
PMID
16819286
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Journal Papers > School of Medicine / Graduate School of Medicine > Thoracic & Cardiovascular Surgery
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