Development of a novel technology to engineer heart muscle for contractile and paracrine support in heart failure

Soong, Poh Loong

dc.contributor.advisor	Zimmermann, Wolfram-Hubertus Prof. Dr.	de
dc.contributor.author	Soong, Poh Loong	de
dc.date.accessioned	2013-01-14T15:35:33Z	de
dc.date.available	2013-08-31T22:50:04Z
dc.date.issued	2012-12-12	de
dc.identifier.uri	http://hdl.handle.net/11858/00-1735-0000-000D-F03B-7	de
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-1659
dc.description.abstract	The human heart has poor endogenous regeneration. If myocytes are lost due to injury, the myocardium is unable to restore its myocyte content and instead undergoes compensatory hypertrophy and remodeling. Cardiac tissue engineering aims to recreate and provide functional myocardium that replaces the injured myocardium. In this study, human engineered heart muscle (EHM) from cardiomyogenically differentiated human embryonic stem cells was generated. EHMs consisted of elongated, anisotropically organized cardiomyocyte bundles and responded “physiologically” to increasing calcium concentrations. To generate large myocardium capable of encompassing the ventricles, a novel process to systematically upscale the dimensions of engineered myocardium to a humanized Biological Ventricular Assisted Device (hBioVAD) was introduced. The hBioVADs formed a “pouch-like” myocardium at rabbit heart dimensions and were beating spontaneously. Further enhancement by biomimetic pulsatile loading generated “more mature” myocardium. Additional paracrine functionality was integrated by generating insulin-like growth factor-1 (IGF-1) secreting fibroblasts for tissue engineering applications. IGF-1 release induced higher levels of Akt phosphorylation and hypertrophy in cardiomyocytes resulting in increased force generation of EHM. Finally, feasibility of “paraBioVAD” (IGF-1 cell line and cardiomyocytes) implantation was demonstrated in a healthy rat model. Histological observations demonstrated engraftment on the heart and the presence of vascular structures. In conclusion, a humanized “paraBioVAD” technology for mechanic and paracrine heart support was developed. Future studies will assess its therapeutic utility in heart failure
dc.format.mimetype	application/pdf	de
dc.language.iso	eng	de
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/	de
dc.title	Development of a novel technology to engineer heart muscle for contractile and paracrine support in heart failure	de
dc.type	doctoralThesis	de
dc.contributor.referee	Zimmermann, Wolfram-Hubertus Prof. Dr.	de
dc.date.examination	2012-10-23	de
dc.subject.dnb	610 Medizin, Gesundheit	de
dc.subject.gok	MED 351 Pharmakologie	de
dc.contributor.coReferee	Wodarz, Andreas Prof. Dr.	de
dc.contributor.thirdReferee	Luther, Stefan Prof. Dr.	de
dc.subject.topic	Medicine	de
dc.subject.ger	Stammzellen	de
dc.subject.ger	humanes Myokard	de
dc.subject.ger	Engineered Heart Muscle	de
dc.subject.ger	EHM	de
dc.subject.ger	humanes biologisches Herzunterstützungsystem (hBioVad)	de
dc.subject.ger	pulsatile Dehnung	de
dc.subject.ger	IGF-1	de
dc.subject.ger	paraBioVAD	de
dc.subject.eng	embryonic stem cells	de
dc.subject.eng	cardiac tissue engineering	de
dc.subject.eng	human engineered heart muscle	de
dc.subject.eng	EHM	de
dc.subject.eng	humanized BioVAD	de
dc.subject.eng	pharmacologically inducible IGF-1	de
dc.subject.eng	paraBioVAD	de
dc.subject.eng	engraftment	de
dc.subject.eng	biomimetic	de
dc.subject.eng	pulsatile	de
dc.subject.bk	44.38 Pharmakologie	de
dc.identifier.urn	urn:nbn:de:gbv:7-webdoc-3838-4	de
dc.identifier.purl	webdoc-3838	de
dc.affiliation.institute	Medizinische Fakultät	de
dc.description.embargoed	2013-08-31	de
dc.description.embargoed	2013-08-31	de
dc.identifier.ppn	773528881

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