Novoheart

: CONTRACTILE MUSCLE

In-house assembled hardware and software dedicated to measuring contractility of hvCTS.

: BIOREACTOR DESIGN

Custom-designed bioreactor enables fabrication and measurement of force and electrophysiology with minimal manipulation.

: HIGH BIOFIDELITY

Sensitive and specific predictor of clinical effects of drugs or pathologies on cardiac contractility.

Novoheart's human ventricular Cardiac Tissue Strip (hvCTS) model is designed to assess cardiac contractility under drug and disease conditions. Benefits include:

- Sensitive and reliable predictor of clinical effects of drugs or pathologies on cardiac contractility

- Custom-designed bioreactor enables tissue fabrication and functional characterization with minimal manipulation

- Measurement of twitch force without complicated instrumentation

- Allows longitudinal studies over days or weeks

hvCTS model is available as two options:

(Cat. No. 3-01) hvCTS bioreactor mold
(Cat. No. 3-02) Drug screening / assessment of cardiac contractility

Cardiac Toxicity Screening: identification of chronotropic and inotropic agents.
Disease Modelling: functional phenotypic characterization for a range of human cardiomyopathies.
Drug Discovery: drug screening and efficacy assessment of chronotropes and inotropes.
Regenerative Studies: studies on contractile maturation, therapeutic mechanisms, and injury repair in human cardiac muscle.

Lee, E. K., Tran, D. D., Keung, W., Chan, P., Wong, G., Chan, C. W., Costa, K. D., Li, R. A. & Khine, M. Machine learning of human pluripotent stem cell-derived engineered cardiac tissue contractility for automated drug classification. Stem Cell Reports. 9, 1560-1572 (2017).

Mayourian J., Cashman T. J., Ceholski D. K., Johnson B. V., Sachs D., Kaji D. A., Sahoo S., Hare J. M., Hajjar R. J., Sobie E. A., Costa K. D. Experimental and Computational Insight Into Human Mesenchymal Stem Cell Paracrine Signaling and Heterocellular Coupling Effects on Cardiac Contractility and Arrhythmogenicity. Circ Res. 121, 411-423 (2017).

Zhang, W., Kong, C. W., Tong, M. H., Chooi, W. H., Huang, N., Li, R. A., Chan, B. P. Maturation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) in 3D collagen matrix: Effects of niche cell supplementation and mechanical stimulation. Acta Biomater. 49, 204-217 (2017).

Stillitano F., Turnbull I. C., Karakikes I., Nonnenmacher M., Backeris P., Hulot J. S., Kranias E. G., Hajjar R. J., Costa K. D. Genomic correction of familial cardiomyopathy in human engineered cardiac tissues. Eur Heart J. 37, 3282-3284 (2016).

Keung, W., Ren, L., Sen Li, Wong, A. O., Chopra, A., Kong, C. W., Tomaselli, G. F., Chen, C. S., Li, R. A. Non-cell autonomous cues for enhanced functionality of human embryonic stem cell-derived cardiomyocytes via maturation of sarcolemmal and mitochrondrial K(ATP) channels. Sci Rep. 6, 34154 (2016).

Cashman, T. J., Josowitz, R., Gelb, B. D., Li, R. A., Dubois, N. C., Costa, K. D., Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy. J Vis Exp. 109, e53447 (2016).

Cashman, T. J., Josowitz, R., Johnson, B. V, Gelb, B. D. & Costa, K. D. Human Engineered Cardiac Tissues Created Using Induced Pluripotent Stem Cells Reveal Functional Characteristics of BRAF-Mediated Hypertrophic Cardiomyopathy. PLoS One 1–17 (2016).

Karakikes, I., Stillitano, F., Nonnenmacher, M., Tzimas, C., Sanoudou, D., Termglinchan, V., Kong, C. W., Rushing, S., Hansen, J., Ceholski, D., Kolokathis, F., Kremastinos, D., Katoulis, A., Ren, L., Cohen, N., Gho, J. M., Tsiapras, D., Vink, A., Wu, J. C., Asselbergs, F. W., Li, R. A., Hulot, J. S., Kranias, E. G., Hajjar, R. J. Correction of human phospholamban R14del mutation associated with cardiomyopathy using targeted nucleases and combination therapy. Nat Commun. 6, 6955 (2015).

Chen, G., Li, S., Karakikes, I., Ren, L., Chow, M. Z., Chopra, A., Keung, W., Yan, B., Chan, C. W. Y., Costa, K. D., Kong, C., Hajjar, R. J., Chen, C. S. & Li, R. A. Phospholamban as a Crucial Determinant of the Inotropic Response of Human Pluripotent Stem Cell – Derived Ventricular Cardiomyocytes and Engineered 3-Dimensional Tissue Constructs. Circ Arrhythm Electrophysiol 8, 193–202 (2015).

Turnbull, I. C., Karakikes, I., Serrao, G. W., Backeris, P., Lee, J. J., Xie, C., Senyei, G., Gordon, R. E., Li, R. A., Akar, F. G., Hajjar, R. J., Hulot, J. & Costa, K. D. Advancing functional engineered cardiac tissues toward a preclinical model of human myocardium. FASEBJ. 28, 644–654 (2014).

Serrao, G. W., Turnbull, I. C., Ancukiewicz, D., Kim, D. E., Kao, E., Cashman, T. J., Hadri, L., Hajjar, R. J. & Costa, K. D. Myocyte-depleted engineered cardiac tissues support therapeutic potential of mesenchymal stem cells. Tissue Eng. Part A 18, 1322–1333 (2012).

Product ID	Product Name	Qty
3-0101	hvCTS mold x 5	1	Request Quote
3-0102	hvCTS mold x 50	1	Request Quote
3-0103	Drug screening / assessment of the cardiac contractility (10 strips) One drug (one concentration), 10 tissue strips will be tested according to our standard protocol using hvCM > 70% purity	1	Request Quote
3-0104	Drug screening / assessment of the cardiac contractility (20 strips) One drug (one concentration), 20 tissue strips will be tested according to our standard protocol using hvCM > 70% purity	1	Request Quote

How many cardiomyocytes are needed for constructing one tissue strip?
Approximately 1 million hvCMs are needed for each tissue strip.

When can the tissue strip be used for the contractility assay?
We recommend allowing tissue strips to develop for 5 to 7 days after creation before the first contractility assay.

How can the bioreactor molds be sterilized?
We recommend sterilization by autoclaving.

Are the bioreactor molds reusable?
Yes. However, we recommend that the molds to be replaced after 5 uses.

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