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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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 α-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.

Original languageEnglish
Pages (from-to)273-283
Number of pages11
JournalExperimental and Molecular Medicine
Volume38
Issue number3
DOIs
Publication statusPublished - 2006 Jun 30

Fingerprint

Heart Valves
Glutaral
Tissue Engineering
Tissue engineering
Bone Marrow Cells
Prosthetics
Bone
Swine
Prostheses and Implants
Endothelial cells
Cell Proliferation
Endothelial Cells
Biocompatibility
Citric Acid
Durability
Prosthesis Failure
Heart Valve Diseases
Myofibroblasts
Proliferating Cell Nuclear Antigen
Cell proliferation

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Kim, Sang Soo ; Lim, Sang Hyun ; Cho, Seung-Woo ; Gwak, So Jung ; Hong, Yoo Sun ; Byung, Chul Chang ; Moon, Hyang Park ; Kang, Won Song ; Cha, Yong Choi ; Kim, Byung Soo. / Tissue engineering of heart valves by recellularization of glutaraldehyde-fixed porcine valves using bone marrow-derived cells. In: Experimental and Molecular Medicine. 2006 ; Vol. 38, No. 3. pp. 273-283.
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Tissue engineering of heart valves by recellularization of glutaraldehyde-fixed porcine valves using bone marrow-derived cells. / Kim, Sang Soo; Lim, Sang Hyun; Cho, Seung-Woo; Gwak, So Jung; Hong, Yoo Sun; Byung, Chul Chang; Moon, Hyang Park; Kang, Won Song; Cha, Yong Choi; Kim, Byung Soo.

In: Experimental and Molecular Medicine, Vol. 38, No. 3, 30.06.2006, p. 273-283.

Research output: Contribution to journalArticle

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AU - Kim, Sang Soo

AU - Lim, Sang Hyun

AU - Cho, Seung-Woo

AU - Gwak, So Jung

AU - Hong, Yoo Sun

AU - Byung, Chul Chang

AU - Moon, Hyang Park

AU - Kang, Won Song

AU - Cha, Yong Choi

AU - Kim, Byung Soo

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AB - 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 α-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.

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