Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique
Abstract There is great interest in the development of techniques to bioengineer pulsatile myocardial tissue as a next-generation regenerative therapy for severe heart failure. However, creation of thick myocardial grafts for regenerative medicine requires the incorporation of blood vessels. In this...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-03-01
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| Series: | npj Regenerative Medicine |
| Online Access: | https://doi.org/10.1038/s41536-022-00218-7 |
| _version_ | 1818773990737444864 |
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| author | Yuki Endo Jun Homma Hidekazu Sekine Katsuhisa Matsuura Tatsuya Shimizu Hiroshi Niinami |
| author_facet | Yuki Endo Jun Homma Hidekazu Sekine Katsuhisa Matsuura Tatsuya Shimizu Hiroshi Niinami |
| author_sort | Yuki Endo |
| collection | DOAJ |
| description | Abstract There is great interest in the development of techniques to bioengineer pulsatile myocardial tissue as a next-generation regenerative therapy for severe heart failure. However, creation of thick myocardial grafts for regenerative medicine requires the incorporation of blood vessels. In this study, we describe a new method of constructing a vascular network in vivo that allows the construction of thick human myocardial tissue from multi-layered cell sheets. A gelatin sheet pre-loaded with growth factors was transplanted onto the superficial femoral artery and vein of the rat. These structures were encapsulated together within an ethylene vinyl alcohol membrane and incubated in vivo for 3 weeks (with distal superficial femoral artery ligation after 2 weeks to promote blood flow to the vascular bed). Subsequently, six cardiomyocyte sheets were transplanted onto the vascular bed in two stages (three sheets, two times). Incubation of this construct for a further week generated vascularized human myocardial tissue with an independent circulation supplied by an artery and vein suitable for anastomosis to host vessels. Notably, laminating six cell sheets on the vascular bed in two stages rather than one allowed the creation of thicker myocardial tissue while suppressing tissue remodeling and fibrosis. Finally, the pulsatile myocardial tissue was shown to generate auxiliary pressure when wrapped around the common iliac artery of a rat. Further development of this technique might facilitate the generation of circulatory assist devices for patients with heart failure. |
| first_indexed | 2024-12-18T10:34:02Z |
| format | Article |
| id | doaj.art-e3fa9743f481477b8ab2bd992cc094f2 |
| institution | Directory Open Access Journal |
| issn | 2057-3995 |
| language | English |
| last_indexed | 2024-12-18T10:34:02Z |
| publishDate | 2022-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Regenerative Medicine |
| spelling | doaj.art-e3fa9743f481477b8ab2bd992cc094f22022-12-21T21:10:48ZengNature Portfolionpj Regenerative Medicine2057-39952022-03-017111010.1038/s41536-022-00218-7Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization techniqueYuki Endo0Jun Homma1Hidekazu Sekine2Katsuhisa Matsuura3Tatsuya Shimizu4Hiroshi Niinami5Department of Cardiovascular Surgery, Tokyo Women’s Medical UniversityInstitute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, TWInsInstitute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, TWInsInstitute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, TWInsInstitute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, TWInsDepartment of Cardiovascular Surgery, Tokyo Women’s Medical UniversityAbstract There is great interest in the development of techniques to bioengineer pulsatile myocardial tissue as a next-generation regenerative therapy for severe heart failure. However, creation of thick myocardial grafts for regenerative medicine requires the incorporation of blood vessels. In this study, we describe a new method of constructing a vascular network in vivo that allows the construction of thick human myocardial tissue from multi-layered cell sheets. A gelatin sheet pre-loaded with growth factors was transplanted onto the superficial femoral artery and vein of the rat. These structures were encapsulated together within an ethylene vinyl alcohol membrane and incubated in vivo for 3 weeks (with distal superficial femoral artery ligation after 2 weeks to promote blood flow to the vascular bed). Subsequently, six cardiomyocyte sheets were transplanted onto the vascular bed in two stages (three sheets, two times). Incubation of this construct for a further week generated vascularized human myocardial tissue with an independent circulation supplied by an artery and vein suitable for anastomosis to host vessels. Notably, laminating six cell sheets on the vascular bed in two stages rather than one allowed the creation of thicker myocardial tissue while suppressing tissue remodeling and fibrosis. Finally, the pulsatile myocardial tissue was shown to generate auxiliary pressure when wrapped around the common iliac artery of a rat. Further development of this technique might facilitate the generation of circulatory assist devices for patients with heart failure.https://doi.org/10.1038/s41536-022-00218-7 |
| spellingShingle | Yuki Endo Jun Homma Hidekazu Sekine Katsuhisa Matsuura Tatsuya Shimizu Hiroshi Niinami Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique npj Regenerative Medicine |
| title | Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique |
| title_full | Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique |
| title_fullStr | Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique |
| title_full_unstemmed | Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique |
| title_short | Bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell-derived cardiomyocytes using a pre-vascularization technique |
| title_sort | bioartificial pulsatile cuffs fabricated from human induced pluripotent stem cell derived cardiomyocytes using a pre vascularization technique |
| url | https://doi.org/10.1038/s41536-022-00218-7 |
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