Name: automated contraction analysis of human engineered heart tissue for cardiac drug safety screening
Uploaded: 2017-04-15T13:00:00
Description: Watch this Scientific Journal Video about Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening at JoVE.com

Forfatterne er takknemlige for Alessandra Moretti og Dennis Schade for deres type bidrag materiale. Vi erkjenner den store støtte fra iPS og EHT arbeidsgruppe ved Institutt for eksperimentell farmakologi og toksikologi ved UKE. Arbeidet med forfatterne er støttet med tilskudd fra DZHK (tysk Center for Cardiovascular Research) og den tyske departementet for utdanning og forskning (BMBF), den tyske Research Foundation (DFG Es 88 / 12-1 HA 3423 / 5-1 ), British National Centre for Replacement Refinement &amp; Reduksjon av dyr i forskning (NC3Rs CRACK-IT innvilge 35911-259146), British Heart Foundation RM / 13/30157, European Research Council (Advanced Grant IndivuHeart), den tyske Heart Foundation og Freie und Hansestadt Hamburg.

MERK: Følgende trinn beskriver en cellekultur protokoll. Vennligst utføre under sterile forhold og bruke forvarmet medier. 1. Cardiac Differensiering av hiPSC <ol><li> Dyrke hiPSC <ol><li> Coat 6-brønners plater (1 ml / brønn) eller T75-kolber (7 ml / kolbe) med redusert vekstfaktor basalmembran matriks (f.eks geltrex, 1: 200; se tabell material) fortynnet i Dulbeccos modifiserte Eagles medium (DMEM) for 30 minutter ved 37 ° C. Forbered FTDA medium <sup class...

<ol>
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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Small+molecule+absorption+by+PDMS+in+the+context+of+drug+response+bioassays.">Small molecule absorption by PDMS in the context of drug response bioassays.</a> Biochem Biophysl Res Commun. , (2016).</li><li>Godier-Furn&#233;mont, A. F. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Physiologic+force-frequency+response+in+engineered+heart+muscle+by+electromechanical+stimulation.">Physiologic force-frequency response in engineered heart muscle by electromechanical stimulation.</a> Biomaterials. 60, 82-91 (2015).</li><li>Eng, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Autonomous+beating+rate+adaptation+in+human+stem+cell-derived+cardiomyocytes.">Autonomous beating rate adaptation in human stem cell-derived cardiomyocytes.</a> Nat Commun. 7, 10312 (2016).</li><li>Huebsch, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Miniaturized+iPS-Cell-Derived+Cardiac+Muscles+for+Physiologically+Relevant+Drug+Response+Analyses.">Miniaturized iPS-Cell-Derived Cardiac Muscles for Physiologically Relevant Drug Response Analyses.</a> Sci Rep. 6 (24726), 1-12 (2016).</li><li>Masumoto, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+myocardial+regenerative+potential+of+three-dimensional+engineered+cardiac+tissues+composed+of+multiple+human+iPS+cell-derived+cardiovascular+cell+lineages.">The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages.</a> Sci Rep. 6 (29933), 1-10 (2016).</li><li>Ravenscroft, S. M., Pointon, A., Williams, A. W., Cross, M. J., Sidaway, J. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+Non-myocyte+Cells+Show+Enhanced+Pharmacological+Function+Suggestive+of+Contractile+Maturity+in+Stem+Cell+Derived+Cardiomyocyte+Microtissues.">Cardiac Non-myocyte Cells Show Enhanced Pharmacological Function Suggestive of Contractile Maturity in Stem Cell Derived Cardiomyocyte Microtissues.</a> Toxicol Sci. 152 (1), 99-112 (2016).</li><li>Zhang, J. H., Chung, T. D. Y., Oldenbutg, K. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Simple+Statistical+Parameter+for+Use+in+Evaluation+and+Validation+of+High+Throughput+Screening+Assays.">A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening Assays.</a> J Biomol Screen. 4 (2), 67-73 (1999).</li><li>Vandenburgh, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Durg-screening+platform+based+on+the+contractility+of+tissue-engineered+muscle.">Durg-screening platform based on the contractility of tissue-engineered muscle.</a> Muscle Nerve. 37 (4), 438-447 (2008).</li></ol>

Konstruert hjertet vev tilbyr en verdifull mulighet til verktøykasse av kardiovaskulær forskning. EHTs i 24-brønners-formatet har vist seg verdifull for sykdom modellering 8, 14, narkotika sikkerhet screening 7, 8, 10, 11, 15, eller basisk Cardiovascular Research 16,</s...

Hjerte bivirkninger som legemiddelindusert lang QT-syndrom har ført til markeds uttak i løpet av de siste årene. Statistikk viser at ca 45% av alle uttak skyldes uønskede effekter på det kardiovaskulære systemet 1. Dette stoffet svikt etter den dyre utviklingsprosess og godkjenning er det verst tenkelige scenario for farmasøytiske selskaper. Forskning og utvikling avdelinger fokuserer derfor på påvisning av slike uønskede kardiovaskulære effekter tidlig. Av økonomiske og etiske hensyn, innsats for å redusere dyreforsøk og erstatte dem med nye in vitro screening-analyser er pågående. Et sett av etablerte analyser er inkludert i USA Food and Drug Administration (FDA) og European Medicines Agency (EMA) retningslinjer for preklinisk vurdering av Proarytmisk virkninger av rusmidler 2. Teknologien for omprogrammering av somatiske celler, etterfulgt av differensiering avhumane induserte pluripotente stamceller (hiPSC) styrket dette forskningsområde 3. Det tilbyr nå muligheten til å screene nye legemiddelkandidater om menneske cardiomyocytes in vitro og unngår problemer med inter-artsforskjeller. Siste hjerte differensiering protokoller 4, 5 gir ubegrenset tilførsel av cardiomyocytes uten etisk bekymring. Imidlertid måling av kontraktile kraft, den viktigste og best karakteriserte in vivo parameter av kardiomyocytter, er ikke godt etablert. Dette er relatert til den relative umodenhet 6 av menneskeskapte pluripotent stamcelle-avledet kardiomyocytter (hiPSC-CM) som sammenlignet med den voksne cardiomyocyte. En mulig forbedring er å konstruere tre-dimensjonale hjertevev fra enkeltceller 7 (utviklet hjertevevet, EHT). Den EHT-protokollen er basert på innstøping enkelt murine eller humane kardiomyocytter 8 </sup&gt;, 9, 10 i fibrin hydrogel mellom to fleksible polydimetylsiloksan (PDMS) innlegg 11 i 24-brønners format. Innen få dager cardiomyocytes begynner å trekke seg sammen spontant som enkeltceller og begynne å danne mobilnettverk. Etter 7-10 dager ble makroskopiske sammentrekninger av hele vev er synlige. Under denne prosessen den ekstracellulære matriks er ombygd, noe som fører til en minskning av diameter og lengde. Forkortelsen av EHT resulterer i bøying av PDMS legge til og med under hvile, underkaste kardiomyocytter i fremkallings EHT til kontinuerlig belastning. EHTs fortsette å utføre auxotonic muskelsammentrekninger over flere uker. Humane EHTs viser respons på fysiologisk og farmakologisk stimulering indikerer at de er egnet for legemiddelscreening og sykdom modellering 7. I dette manuskriptet presenterer vi en robust og enkel protokoll for generasjon avpå fra human EHT, og den automatiserte kontraktilitet analyse av konsentrasjonsavhengige forandringer i den sammentrekning mønster i nærvær av hERG kanal inhibitorer.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>EHT analysis intrument</td>
			<td>EHT Technologies GmbH</td>
			<td>A0001</td>
			<td>Software is included</td>
		</tr>
		<tr>
			<td>EHT PDMS rack</td>
			<td>EHT Technologies GmbH</td>
			<td>C0001</td>
			<td></td>
		</tr>
		<tr>
			<td>EHT PTFE spacer</td>
			<td>EHT Technologies GmbH</td>
			<td>C0002</td>
			<td></td>
		</tr>
		<tr>
			<td>EHT electrode</td>
			<td>EHT Technologies GmbH</td>
			<td>P0001</td>
			<td></td>
		</tr>
		<tr>
			<td>EHT pacing adapter/cable</td>
			<td>EHT Technologies GmbH</td>
			<td>P0002</td>
			<td></td>
		</tr>
		<tr>
			<td>24-well-plate</td>
			<td>Nunc</td>
			<td>144530</td>
			<td></td>
		</tr>
		<tr>
			<td>6 well-cell culture plate</td>
			<td>Nunc</td>
			<td>140675</td>
			<td></td>
		</tr>
		<tr>
			<td>15 ml falcon tube, graduated&#160;</td>
			<td>Sarstedt</td>
			<td>62,554,502</td>
			<td></td>
		</tr>
		<tr>
			<td>Cell scraper</td>
			<td>Sarstedt</td>
			<td>831,830</td>
			<td></td>
		</tr>
		<tr>
			<td>Spinner flask</td>
			<td>Integra</td>
			<td>182 101</td>
			<td></td>
		</tr>
		<tr>
			<td>Stirrer Variomag/ Cimarec Biosystem Direct&#160;</td>
			<td>Thermo scientific</td>
			<td>70101</td>
			<td>Adjust rotor speed to 40 rpm</td>
		</tr>
		<tr>
			<td>T175 cell culture flask&#160;</td>
			<td>Sarstedt&#160;</td>
			<td>831,812,002</td>
			<td></td>
		</tr>
		<tr>
			<td>V-shaped sedimentation rack&#160;</td>
			<td>Custom made at UKE Hamburg</td>
			<td>na</td>
			<td></td>
		</tr>
		<tr>
			<td>10&#215; DMEM</td>
			<td>Gibco</td>
			<td>52100</td>
			<td></td>
		</tr>
		<tr>
			<td>1-Thioglycerol&#160;</td>
			<td>Sigma Aldrich</td>
			<td>M6145</td>
			<td></td>
		</tr>
		<tr>
			<td>2-Phospho-L-ascorbic acid trisodium salt</td>
			<td>Sigma Aldrich</td>
			<td>49752</td>
			<td></td>
		</tr>
		<tr>
			<td>Activin-A&#160;</td>
			<td>R&#38;D systems</td>
			<td>338-AC</td>
			<td></td>
		</tr>
		<tr>
			<td>Agarose&#160;</td>
			<td>Invitrogen</td>
			<td>15510-019</td>
			<td></td>
		</tr>
		<tr>
			<td>Aprotinin</td>
			<td>Sigma Aldrich</td>
			<td>A1153</td>
			<td></td>
		</tr>
		<tr>
			<td>Aqua ad injectabilia</td>
			<td>Baxter GmbH</td>
			<td>1428</td>
			<td></td>
		</tr>
		<tr>
			<td>B27 PLUS insulin&#160;</td>
			<td>Gibco</td>
			<td>17504-044</td>
			<td></td>
		</tr>
		<tr>
			<td>BMP-4</td>
			<td>R&#38;D systems</td>
			<td>314-BP</td>
			<td></td>
		</tr>
		<tr>
			<td>Collagenase II&#160;</td>
			<td>Worthington</td>
			<td>LS004176</td>
			<td></td>
		</tr>
		<tr>
			<td>DMEM</td>
			<td>Biochrom</td>
			<td>F0415</td>
			<td></td>
		</tr>
		<tr>
			<td>DMSO&#160;</td>
			<td>Sigma Aldrich</td>
			<td>D4540</td>
			<td></td>
		</tr>
		<tr>
			<td>DNase II, type V (from bovine spleen)</td>
			<td>Sigma&#160;</td>
			<td>D8764</td>
			<td></td>
		</tr>
		<tr>
			<td>Dorsomorphin&#160;</td>
			<td>abcam</td>
			<td>ab120843</td>
			<td></td>
		</tr>
		<tr>
			<td>EDTA&#160;</td>
			<td>Roth</td>
			<td>8043.2</td>
			<td></td>
		</tr>
		<tr>
			<td>Fetal calf serum</td>
			<td>Gibco</td>
			<td>10437028</td>
			<td></td>
		</tr>
		<tr>
			<td>FGF2</td>
			<td>Miltenyi Biotec</td>
			<td>130-104-921</td>
			<td></td>
		</tr>
		<tr>
			<td>Fibrinogen (bovine)</td>
			<td>Sigma Aldrich</td>
			<td>F8630</td>
			<td></td>
		</tr>
		<tr>
			<td>Geltrex&#160;</td>
			<td>Gibco</td>
			<td>A1413302</td>
			<td>For coating: 1:200 dilution</td>
		</tr>
		<tr>
			<td>HBSS w/o Ca2+/Mg2+&#160;</td>
			<td>Gibco</td>
			<td>14175-053</td>
			<td></td>
		</tr>
		<tr>
			<td>HEPES&#160;</td>
			<td>Roth</td>
			<td>9105.4</td>
			<td></td>
		</tr>
		<tr>
			<td>Horse serum</td>
			<td>Life technologies</td>
			<td>26050088</td>
			<td></td>
		</tr>
		<tr>
			<td>Human serum albumin&#160;</td>
			<td>Biological Industries</td>
			<td>05-720-1B</td>
			<td></td>
		</tr>
		<tr>
			<td>Insulin, human</td>
			<td>Sigma Aldrich</td>
			<td>I9278</td>
			<td></td>
		</tr>
		<tr>
			<td>L-Glutamin</td>
			<td>Gibco</td>
			<td>25030-024</td>
			<td></td>
		</tr>
		<tr>
			<td>Lipidmix&#160;</td>
			<td>Sigma Aldrich</td>
			<td>L5146</td>
			<td></td>
		</tr>
		<tr>
			<td>Matrigel</td>
			<td>BD Biosciences</td>
			<td>354234</td>
			<td>For EHT reconsitutionmix.</td>
		</tr>
		<tr>
			<td>N-Benzyl-p-Toluenesulfonamide</td>
			<td>TCI</td>
			<td>B3082-25G</td>
			<td></td>
		</tr>
		<tr>
			<td>PBS w/o MgCl2/CaCl2</td>
			<td>Biochrom</td>
			<td>14190</td>
			<td></td>
		</tr>
		<tr>
			<td>Penicillin/Streptomycin</td>
			<td>Gibco</td>
			<td>15140</td>
			<td></td>
		</tr>
		<tr>
			<td>Pluronic F-127&#160;</td>
			<td>Sigma Aldrich</td>
			<td>P2443</td>
			<td></td>
		</tr>
		<tr>
			<td>Polyvinyl alcohol&#160;</td>
			<td>Sigma Aldrich</td>
			<td>P8136</td>
			<td></td>
		</tr>
		<tr>
			<td>RPMI 1640&#160;</td>
			<td>Gibco</td>
			<td>21875</td>
			<td></td>
		</tr>
		<tr>
			<td>Sodium selenite</td>
			<td>Sigma Aldrich</td>
			<td>S5261</td>
			<td></td>
		</tr>
		<tr>
			<td>TGF&#223;1</td>
			<td>Peprotech</td>
			<td>100-21</td>
			<td></td>
		</tr>
		<tr>
			<td>Thrombin</td>
			<td>Sigma Aldrich</td>
			<td>T7513</td>
			<td></td>
		</tr>
		<tr>
			<td>Transferrin&#160;</td>
			<td>Sigma Aldrich</td>
			<td>T8158</td>
			<td></td>
		</tr>
		<tr>
			<td>Y-27632</td>
			<td>Biorbyt</td>
			<td>orb6014</td>
			<td></td>
		</tr>
		<tr>
			<td>hiPSC</td>
			<td>Custom made at UKE hamburg</td>
			<td>na</td>
			<td></td>
		</tr>
		<tr>
			<td>iCell cardiomyocytes kit</td>
			<td>Cellular Dynamics International</td>
			<td>CMC-100-010-001</td>
			<td></td>
		</tr>
		<tr>
			<td>Pluricyte cardiomyocyte kit</td>
			<td>Pluriomics</td>
			<td>PCK-1.5</td>
			<td></td>
		</tr>
		<tr>
			<td>Cor.4U - HiPSC cardiomyocytes kit</td>
			<td>Axiogenesis AG</td>
			<td>Ax-C-HC02-FR3</td>
			<td></td>
		</tr>
		<tr>
			<td>Cellartis cardiomyocytes</td>
			<td>Takara Bio USA, Inc.</td>
			<td>Y10075</td>
			<td></td>
		</tr>
	</tbody>
</table>

automated contraction analysis of human engineered heart tissue for cardiac drug safety screening

Hjertevev teknikk beskrives teknikker for å danne tredimensjonale kraftgenerer utviklet vev. For gjennomføring av disse prosedyrene i grunnforskning og prekliniske narkotika utvikling, er det viktig å utvikle protokoller for automatisert produksjon og analyse under standardiserte betingelser. Her presenterer vi en teknikk for å generere Engineered hjertevevet (EHT) fra kardiomyocytter fra forskjellige arter (rotte, mus, menneske). Teknikken er basert på montering av en fibrin-gel inneholdende dissosierte kardiomyocytter mellom elastisk polydimetylsiloksan (PDMS) poster i en 24-brønners format. Tredimensjonal, kraftgenererende EHTs utgjør i løpet av to uker etter støping. Denne prosedyren tillater generering av flere hundre EHTs per uke og er teknisk begrenset av tilgjengeligheten av cardiomyocytes (0,4-1,0 x 10 6 / EHT). Evaluering av auxotonic muskelsammentrekninger blir utført i en modifisert inkubasjon kammer med en mechanical sperre for 24-brønners plater og et kamera plassert på toppen av dette kammer. En programvare styrer et kamera beveget på en XYZ aksesystem til hver EHT. EHT trekningene detekteres ved hjelp av en automatisk gjenkjennelse figur algoritme, og kraft blir beregnet basert på forkortning av høyspenningen og den elastiske tilbøyelighet og geometri av PDMS innlegg. Denne fremgangsmåten gjør det mulig for automatisk analyse av et høyt antall EHT under standardiserte og sterile betingelser. Den pålitelige påvisning av narkotika effekter på cardiomyocyte sammentrekning er avgjørende for hjertelegemiddelutvikling og sikkerhetsfarmakologi. Vi viser, med det eksempel på den hERG kanal inhibitor E-4031, som det menneskelige EHT-systemet reproduserer legemiddel svarene på sammentrekningskinetikken til det menneskelige hjerte, noe som indikerer at det skal være et viktig verktøy for hjerte medikament sikkerhet screening.

Cardiac Differensiering og fremstilling av EHT HiPSC ble ekspandert på grunn av redusert vekstfaktor basalmembran matrise, dissosiert med EDTA og embryoidlegemer (EBS) dannet i spinnerflasker over natten. Etter mesodermal induksjon i tre dager, ble hjerte differensiering initiert med Wnt inhibitor. Etter ~ 17 dager med differensiering protokollen, ble slo EBS dissosiert til enkeltceller med kollagenase type II (figur 1)....

Watch this Scientific Journal Video about Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening at JoVE.com

Automated Contraction Analysis of Human Engineered Heart Tissue for Cardiac Drug Safety Screening

Her viser vi generering av human konstruert hjertevev fra induserte pluripotente stamceller (hiPSC) -avledede kardiomyocytter. Vi presenterer en metode for å analysere kontraksjonskraft og eksempelvise endring av sammentrekning mønster av hERG kanal inhibitor E-4031. Denne fremgangsmåten viser høy grad av robusthet og egnethet for hjertelegemiddelscreening.

Automatisert Sammentrekning Analysis of Human Engineered hjertevev for Cardiac Drug Safety Screening

Cardiac tissue engineering describes techniques to constitute three dimensional force-generating engineered tissues. For the implementation of these ...

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Cardiovascular Drugs: Antiarrhythmic and Heart Failure Drugs

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Bioluminescence Imaging for Assessment of Immune Responses Following Implantation of Engineered Heart Tissue (EHT)

Bioluminescence Imaging for Assessment of Immune Responses Following Implantation of Engineered Heart Tissue EHT

Various techniques of cardiac tissue engineering have been pursued in the past decades including scaffolding strategies using either native or ...

Self-reporting Scaffolds for 3-Dimensional Cell Culture

Egenrapportering Stillaser for 3-dimensjonal Cell Culture

Culturing cells in 3D on appropriate scaffolds is thought to better mimic the in vivo microenvironment and increase cell-cell interactions. The resulting ...

Analysis of Tubular Membrane Networks in Cardiac Myocytes from Atria and Ventricles

Analyse av Tubular Membran Networks i hjertemuskelceller fra Atria og ventriklene

In cardiac myocytes a complex network of membrane tubules - the transverse-axial tubule system (TATS) - controls deep intracellular signaling functions. ...

Hollow Fiber Bioreactors for In Vivo-like Mammalian Tissue Culture

Hollow Fiber Bioreactors for In Vivo-like Mammalian Tissue Culture

Hollow Fiber Bioreaktorer for<em&gt; I Vivo</em&gt; -lignende Pattedyr Tissue Culture

Tissue culture has been used for over 100 years to study cells and responses ex vivo. The convention of this technique is the growth of anchorage ...

Construction of Defined Human Engineered Cardiac Tissues to Study Mechanisms of Cardiac Cell Therapy

Bygging av Definert menneske Engineered Hjerte Vev å studere mekanismer Cardiac Cell Therapy

Human cardiac tissue engineering can fundamentally impact therapeutic discovery through the development of new species-specific screening systems that ...

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

A Combined 3D Tissue Engineered In Vitro/In Silico Lung Tumor Model for Predicting Drug Effectiveness in Specific Mutational Backgrounds

En Kombinert 3D Tissue Konstruert<em&gt; In Vitro</em&gt; /<em&gt; I Silico</em&gt; Lung Tumor modell for å forutsi Drug Effective i Spesifikke mutasjons bakgrunner

In the present study, we combined an in vitro 3D lung tumor model with an in silico model to optimize predictions of drug response based on a specific ...

Neonatal Cardiac Scaffolds: Novel Matrices for Regenerative Studies

Neonatal Cardiac Stillas: Nye matriser for Regenerative Studies

The only definitive therapy for end stage heart failure is orthotopic heart transplantation.  Each year, it is estimated that more than 100,000 donor ...

Use of High-Throughput Automated Microbioreactor System for Production of Model IgG1 in CHO Cells

Bruk av høy gjennomstrømming automatisert Microbioreactor System for produksjon av modellen IgG1 i CHO celler

Automated microscale bioreactors (15 mL) can be a useful tool for cell culture engineers. They facilitate the simultaneous execution of a wide variety of ...

Preparation of Mesh-Shaped Engineered Cardiac Tissues Derived from Human iPS Cells for In Vivo Myocardial Repair

Fremstilling av mesh-formet konstruert hjertevev avledet fra menneskelige iPS-celler for In Vivo myokardreparasjon

The current protocol describes methods to generate scalable, mesh-shaped engineered cardiac tissues (ECTs) composed of cardiovascular cells derived from ...

Cardiac Spheroids as in vitro Bioengineered Heart Tissues to Study Human Heart Pathophysiology

Hjertesfæroider som in vitro bioingeniør hjertevev for å studere humant hjerte patofysiologi

Despite several advances in cardiac tissue engineering, one of the major challenges to overcome remains the generation of a fully functional vascular ...