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

Sang-Soo Kim,So-Jung Gwak,Byung-Soo Kim,Yoo-Sun Hong,Sang-Hyun Lim,Moon Hyang Park,Byung Chul Chang,Seung Woo Cho,Kang Won Song,Cha Yong Choi

doi:10.1038/emm.2006.33

Sang-Soo Kim, So-Jung Gwak + Show 8 more

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https://doi.org/10.1038/emm.2006.33

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Journal: Experimental and Molecular Medicine	Publication Date: Jun 1, 2006
Citations: 32	License type: cc-by

Affiliation: Hanyang University

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.

Highlights

Replacement of heart valves with mechanical or biological prostheses is currently a common treatment for end-stage valvular diseases (Lupinetti et al, 1997)
Differentiation and characterization of bone marrow-derived cell (BMC) Cultured canine BMCs were able to differentiate into endothelial cell (EC)-like cells and MF-like cells in vitro
The mRNA markers of ECs, endothelial nitric oxide synthase and kinase-insert domain-containing receptor (KDR), were expressed at a higher extent in the BMCs cultured in the EC-like cell culture condition than freshly isolated bone marrow mononuclear cells (MNCs) and cells cultured in the MF-like cell culture condition

Summary

Introduction

Replacement of heart valves with mechanical or biological prostheses is currently a common treatment for end-stage valvular diseases (Lupinetti et al, 1997). These heart valve prostheses substantially reduce the mortality of patients, but the prostheses have severe limitations. The major disadvantage of GA-fixed tissue valve prostheses is the degeneration of grafts, with subsequent calcification and tissue failure (Sodian et al, 2000) This may result from an inability of host cells to repopulate the valve due to the GA-fixation process (Yacoub et al, 1995)

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