Engineering of functional cardiac tubes by stepwise transplantation of cardiac cell sheets onto intestinal mesentery

Masuda, Noriyasu; Sekine, Hidekazu; Niinami, Hiroshi; Shimizu, Tatsuya

doi:10.1007/s00380-019-01550-7

Cited by 4 publications

(3 citation statements)

References 22 publications

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“…The rod-shaped EHTs reportedly exhibit maturation and polarity of cells. Previously, scientists have created tubular EHTs by rolling sheet-type EHTs over a tube, resulting in engraftment and pulsation of the tube ( 14 , 15 ). In the present study, we fabricated T-EHTs using a bio-3D printer with a needle array.…”

Section: Discussionmentioning

confidence: 99%

Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo

Kawai

Tohyama

Arai

et al. 2022

Front. Cardiovasc. Med.

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Engineered heart tissues (EHTs) that are fabricated using human induced pluripotent stem cells (hiPSCs) have been considered as potential cardiac tissue substitutes in case of heart failure. In the present study, we have created hiPSC-derived cardiac organoids (hiPSC-COs) comprised of hiPSC-derived cardiomyocytes, human umbilical vein endothelial cells, and human fibroblasts. To produce a beating conduit for patients suffering from congenital heart diseases, we constructed scaffold-free tubular EHTs (T-EHTs) using hiPSC-COs and bio-3D printing with needle arrays. The bio-3D printed T-EHTs were cut open and transplanted around the abdominal aorta as well as the inferior vena cava (IVC) of NOG mice. The transplanted T-EHTs were covered with the omentum, and the abdomen was closed after completion of the procedure. Additionally, to compare the functionality of hiPSC-COs with that of T-EHTs, we transplanted the former around the aorta and IVC as well as injecting them into the subcutaneous tissue on the back of the mice. After 1 m of the transplantation procedures, we observed the beating of the T-EHTs in the mice. In histological analysis, the T-EHTs showed clear striation of the myocardium and vascularization compared to hiPSC-COs transplanted around the aorta or in subcutaneous tissue. Based on these results, bio-3D-printed T-EHTs exhibited a better maturation in vivo as compared to the hiPSC-COs. Therefore, these beating T-EHTs may form conduits for congenital heart disease patients, and T-EHT transplantation can form a treatment option in such cases.

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Section: Discussionmentioning

confidence: 99%

Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo

Kawai

Tohyama

Arai

et al. 2022

Front. Cardiovasc. Med.

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“…In other experiments (double-step group), one heart tube was implanted into the mesentery, and a second heart tube was inserted into the original tube one day later after a sufficient number of new blood vessels had been created in the first transplanted tube. Spontaneous pulsations were observed in the cardiac tubes from the first week after transplantation, and the mean internal pressure at four weeks after transplantation was 1.8 ± 1.0 mmHg in the single-step group and 2.5 ± 0.3 mmHg in the double-step group, suggesting that increasing the number of cell sheet layers improved the functionality of the cardiac tube [34]. These findings demonstrate that it is feasible to use the mesentery as a vascular bed for the creation of functional cardiac tubes.…”

Section: Cell Sheet-based Vascularization Approachesmentioning

confidence: 95%

Capillary Networks for Bio-Artificial Three-Dimensional Tissues Fabricated Using Cell Sheet Based Tissue Engineering

Sekine

Okano

2020

IJMS

Self Cite

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One of the most important challenges facing researchers in the field of regenerative medicine is to develop methods to introduce vascular networks into bioengineered tissues. Although cell scaffolds that slowly release angiogenic factors can promote post-transplantation angiogenesis, they cannot be used to construct thick tissues because of the time required for sufficient vascular network formation. Recently, the co-culture of graft tissue with vascular cells before transplantation has attracted attention as a way of promoting capillary angiogenesis. Although the co-cultured vascular cells can directly contribute to blood vessel formation within the tissue, a key objective that needs to be met is the construction of a continuous circulatory structure. Previously described strategies to reconstruct blood vessels include the culture of endothelial cells in a scaffold that contains microchannels or within the original vascular framework after decellularization of an entire organ. The technique, as developed by authors, involves the progressive stacking of three-layered cell sheets onto a vascular bed to induce the formation of a capillary network within the cell sheets. This approach enables the construction of thick, functional tissue of high cell density that can be transplanted by anastomosing its artery and vein (provided by the vascular bed) with host blood vessels.

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“…This cell sheet can be transferred to the tissue or organ surface in the body, or to another culture dish. They can also be obtained as a 3-dimensional structure by attaching the cell sheets on top of each other [7][8][9][10][11]. This method allows the target tissue to be designed in 3D.…”

Section: Introductionmentioning

confidence: 99%

Production of alginate macrocapsule device for long-term normoglycaemia in the treatment of type 1 diabetes mellitus with pancreatic cell sheet engineering

Duman,

Yazir,

Halbutoğullari

et al. 2024

Biomed. Mater.

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Type-1 diabetes mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again. In this study, we aimed to design the most suitable cell-sheet treatment method and macrocapsule device for cell-sheets that could provide long-term normoglycemia in rats. In this study, we developed a macrodevice system designed for insulin delivery to an extrahepatic transplant site using alginate hydrogels of varying concentrations. Firstly, mesenchymal stem cells (MSCs) and beta cells were co-cultured in a temperature-responsive culture dish to obtain a cell-sheet and then macroencapsulated in 2% alginate. The mechanical properties and pore-sizes of the macrocapsule device from alginate were characterized. The viability and activity of cell-sheets in the macrocapsule were evaluated in-vitro and in-vivo. Fasting blood glucose levels, body weight, and serum insulin and C-peptide levels were evaluated after transplantation in diabetic rats. The results showed that the blood glucose level was 225 mg/dl on the 10th day and 168 mg/dl on the 15th day, and remained at the normoglycemic level for 210 days after transplantation. An alginate macrocapsule device has been developed in this study to protect the cell-sheet from immune attack after subcutaneous transplantation and allow the graft to function for a long time as an alternative to pancreatic islet transplantation to patients with T1DM in the future. The results of our study provide the basis for future animal and human studies in which this method can be used to provide long-term cellular therapy in T1DM patients.

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Engineering of functional cardiac tubes by stepwise transplantation of cardiac cell sheets onto intestinal mesentery

Cited by 4 publications

References 22 publications

Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo

Scaffold-Free Tubular Engineered Heart Tissue From Human Induced Pluripotent Stem Cells Using Bio-3D Printing Technology in vivo

Capillary Networks for Bio-Artificial Three-Dimensional Tissues Fabricated Using Cell Sheet Based Tissue Engineering

Production of alginate macrocapsule device for long-term normoglycaemia in the treatment of type 1 diabetes mellitus with pancreatic cell sheet engineering

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