Generation of a large-scale vascular bed for the in vitro creation of three-dimensional cardiac tissue
| Autor: | Hidekazu Sekine, Minoru Ono, Akitoshi Inui, Kazunori Sano, Eiji Kobayashi, Katsuhisa Matsuura, Tatsuya Shimizu, Izumi Dobashi, Azumi Yoshida |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty HUVECs human umbilical vein endothelial cells Angiogenesis Biomedical Engineering HE hematoxylin/eosin DMEM Dulbecco's Modified Eagle Medium Regenerative medicine Vascular bed Biomaterials 03 medical and health sciences 0302 clinical medicine bFGF basic fibroblast growth factor Tissue engineering medicine.artery Medicine Superior mesenteric artery lcsh:QH573-671 Superior mesenteric vein hiPSC human induced pluripotent stem cells PERV porcine endogenous retrovirus GFP green fluorescent protein lcsh:R5-920 hiPSCs lcsh:Cytology business.industry 3D three-dimensional medicine.disease NHDFs normal human dermal fibroblasts VEGF vascular endothelial growth factor Small intestine ECM extracellular matrix Transplantation 030104 developmental biology medicine.anatomical_structure Cardiac cell sheet Heart failure Original Article Perfusion culture lcsh:Medicine (General) business 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Regenerative Therapy Regenerative Therapy, Vol 11, Iss, Pp 316-323 (2019) |
| ISSN: | 2352-3204 |
| Popis: | Introduction: The definitive treatment for severe heart failure is transplantation. However, only a small number of heart transplants are performed each year due to donor shortages. Therefore, novel treatment approaches based on artificial organs or regenerative therapy are being developed as alternatives. We have developed a technology known as cell sheet-based tissue engineering that enables the fabrication of functional three-dimensional (3D) tissue. Here, we report a new technique for engineering human cardiac tissue with perfusable blood vessels. Our method involved the layering of cardiac cell sheets derived from human induced pluripotent stem cells (hiPSCs) on a vascular bed derived from porcine small intestinal tissue. Methods: For the vascular bed, a segment of porcine small intestine was harvested together with a branch of the superior mesenteric artery and a branch of the superior mesenteric vein. The small intestinal tissue was incised longitudinally, and the mucosa was resected. Human cardiomyocytes derived from hiPSCs were co-cultured with endothelial cells and fibroblasts on a temperature-responsive dish and harvested as a cardiac cell sheet. A triple-layer of cardiac cell sheets was placed onto the vascular bed, and the resulting construct was subjected to perfusion culture in a bioreactor system. Results: The cardiac tissue on the vascular bed pulsated spontaneously and synchronously after one day of perfusion culture. Electrophysiological recordings revealed regular action potentials and a beating rate of 105 ± 13/min (n = 8). Furthermore, immunostaining experiments detected partial connection of the blood vessels between the vascular bed and cardiac cell sheets. Conclusions: We succeeded in engineering spontaneously beating 3D cardiac tissue in vitro using human cardiac cell sheets and a vascular bed derived from porcine small intestine. Further development of this method might allow the fabrication of functional cardiac tissue that could be used in the treatment of severe heart failure. Keywords: Cardiac cell sheet, Vascular bed, Perfusion culture, hiPSCs, Angiogenesis |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|