Cell sheet transplantation for heart tissue repair

Matsuura, Kiyotaka; Haraguchi, Yuji; Okano, Teruo

doi:10.1016/j.jconrel.2013.03.003

Cited by 56 publications

(56 citation statements)

References 39 publications

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“…12 However, after enzymatic dissociation of EBs to a single cell suspension and 4-5 days of culture in DMEM supplemented with 10% FBS, Oct3/4-expressing undifferentiated iPS cells are undetectable. 13 Consistent with these previous findings, the expression of OCT3/4 and NANOG was downregulated in both condition 1 and 2 compared with that in cells just after cardiac differentiation (Fig. 3B).…”

Section: Methionine Is Critical For the Survival And Growth Of Human supporting

confidence: 92%

“…Briefly, at 2 days after starting the culture in the bioreactor system with mTeSR1, EBs were cultured in StemPro34 medium containing 50 mg/mL ascorbic acid (Sigma-Aldrich, St. Louis, MO), 2 mM L-glutamine (Life Technologies), and 400 mM 1-thioglycerol (Sigma-Aldrich). The cells were then treated with 0.5 ng/mL bone morphogenic protein-4 (R&D systems, Minneapolis, MN) (days 2-3), 10 ng/mL bone morphogenic protein-4 (days 3-6), 5 ng/mL bFGF (days 3-6), 3 ng/mL activin A (R&D Systems) (days 3-6), 4 mM IWR-1 (Wako, Osaka, Japan) (days 6-8), 5 ng/mL vascular endothelial growth factor (R&D Systems) (days [8][9][10][11][12][13][14][15][16][17][18], and 10 ng/mL bFGF (days [8][9][10][11][12][13][14][15][16][17][18]. Before seeding the cells, the surfaces of temperature-responsive dishes (UpCell; CellSeed, Tokyo, Japan) were coated with FBS for 2 h. After cardiac differentiation, the cells were dissociated with 0.05% trypsin/EDTA, cell aggregates were removed using a strainer (BD Biosciences, San Jose, CA), and single cells were plated onto the UpCell at 2.1 · 10 5 cells/cm 2 in DMEM supplemented with 10% FBS at 37°C in a humidified atmosphere with 5% CO 2 .…”

Section: Cardiac Differentiation In the Bioreactor And Cardiac Cell Smentioning

confidence: 99%

“…These culture conditions are unconventional for human iPS cells, which decrease the contamination of iPS cells to below microscopically detectable levels. 13 However, because around 1000 million cardiomyocytes are assumed to be lost after myocardial infarction, minimum transplantation of over 100 million cells is thought to be necessary for cardiac regenerative therapy using iPS cell-derived cells. Therefore, further efforts are needed to eliminate the very small amount of remaining iPS cells for such a high number of transplanted cells to prevent tumor formation upon engraftment.…”

Section: Introductionmentioning

confidence: 99%

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Elimination of Remaining Undifferentiated Induced Pluripotent Stem Cells in the Process of Human Cardiac Cell Sheet Fabrication Using a Methionine-Free Culture Condition

Matsuura

Kodama

Sugiyama

et al. 2015

Tissue Engineering Part C: Methods

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Cardiac tissue engineering is a promising method for regenerative medicine. Although we have developed human cardiac cell sheets by integration of cell sheet-based tissue engineering and scalable bioreactor culture, the risk of contamination by induced pluripotent stem (iPS) cells in cardiac cell sheets remains unresolved. In the present study, we established a novel culture method to fabricate human cardiac cell sheets with a decreased risk of iPS cell contamination while maintaining viabilities of iPS cell-derived cells, including cardiomyocytes and fibroblasts, using a methionine-free culture condition. When cultured in the methionine-free condition, human iPS cells did not survive without feeder cells and could not proliferate or form colonies on feeder cells or in coculture with cells for cardiac cell sheet fabrication. When iPS cell-derived cells after the cardiac differentiation were transiently cultured in the methionine-free condition, gene expression of OCT3/4 and NANOG was downregulated significantly compared with that in the standard culture condition. Furthermore, in fabricated cardiac cell sheets, spontaneous and synchronous beating was observed in the whole area while maintaining or upregulating the expression of various cardiac and extracellular matrix genes. These findings suggest that human iPS cells are methionine dependent and a methionine-free culture condition for cardiac cell sheet fabrication might reduce the risk of iPS cell contamination.

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Section: Methionine Is Critical For the Survival And Growth Of Human supporting

confidence: 92%

Section: Cardiac Differentiation In the Bioreactor And Cardiac Cell Smentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Elimination of Remaining Undifferentiated Induced Pluripotent Stem Cells in the Process of Human Cardiac Cell Sheet Fabrication Using a Methionine-Free Culture Condition

Matsuura

Kodama

Sugiyama

et al. 2015

Tissue Engineering Part C: Methods

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“…The constructs used for cardiac tissue repair include the implantation of multicellular cardiospheres [18], various formulations of 2D cellular sheets [19][20][21][22], and various formulations of 3D tissues [5][6][7][8]13]. The composition of the noncellular constituents varies from minimal constituents for cardiosphere clusters to a range of ECM components [23,24] and growth factors [25][26][27] selected for their ability to facilitate CM survival and functional maturation.…”

Section: Various Formulations For Engineered Cardiac Tissuesmentioning

confidence: 99%

Engineered Cardiac Tissues Generated from Immature Cardiac and Stem Cell-Derived Cells: Multiple Approaches and Outcomes

Keller

Yuan

et al. 2016

Etiology and Morphogenesis of Congenital Heart Disease

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The translation of in vitro engineered cardiac tissues (ECTs) from immature cardiac and stem cell-derived cells toward clinical therapies is benefiting from the following major advances: (1) rapid progress in the generation of immature cardiac cells from the cardiac and noncardiac cells of multiple species including normal and disease human cells, (2) incorporation of multiple cell lineages into 3D tissues, (3) multiple scalable 3D formulations including injectable gels and implantable tissues, and (4) insights into the regulation of cardiomyocyte proliferation and functional maturation. These advances are based on insights gained from investigating the regulation of cardiac morphogenesis and adaptation. Our lab continues to explore this approach, including changes in gene expression that occur in response to mechanical loading and tyrosine kinase inhibition, the incorporation of vascular fragments into ECTs, and the fabrication of porous implantable electrical sensors for in vitro conditioning and postimplantation testing. Significant challenges remain including optimizing ECT survival postimplantation and limited evidence of ECT functional coupling to the recipient myocardium. One clear focus of current research is the optimization and expansion of the cellular constituents, including CM, required for clinical-grade ECTs. Another major area of investigation will be large animal preclinical models that more accurately represent human CV failure and that can generate data in support of regulatory approval for phase I human clinical trials. The generation of reproducible human ECTs creates the opportunity to develop in vitro myocardial surrogate tissues for novel drug therapeutics and toxicity assays.

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“…The majority of work to date has focused upon cell-based therapies [19][20][21][22][23][24][25][26][27][28]. Of course, any successful approach for creation of functional tissue will require cells, but one strategic variable is the source of cells; i.e., exogenous delivery of harvested allogeneic or autologous cells to the site of interest vs. recruitment of endogenous cells to the site of interest.…”

Section: Introductionmentioning

confidence: 99%