• Deutsch
    • English
  • English 
    • Deutsch
    • English
  • Login
Item View 
  •   Home
  • Medizin
  • Molekulare Medizin
  • Item View
  •   Home
  • Medizin
  • Molekulare Medizin
  • Item View
JavaScript is disabled for your browser. Some features of this site may not work without it.

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

by Poh Loong Soong
Doctoral thesis
Date of Examination:2012-10-23
Date of issue:2012-12-12
Advisor:Prof. Dr. Wolfram-Hubertus Zimmermann
Referee:Prof. Dr. Wolfram-Hubertus Zimmermann
Referee:Prof. Dr. Andreas Wodarz
Referee:Prof. Dr. Stefan Luther
crossref-logoPersistent Address: http://dx.doi.org/10.53846/goediss-1659

 

 

Files in this item

Name:soong.pdf
Size:25.2Mb
Format:PDF
ViewOpen

The following license files are associated with this item:


Abstract

Keywords: embryonic stem cells; cardiac tissue engineering; human engineered heart muscle; EHM; humanized BioVAD; pharmacologically inducible IGF-1; paraBioVAD; engraftment; biomimetic; pulsatile

Other Languages

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
Schlagwörter: Stammzellen; humanes Myokard; Engineered Heart Muscle; EHM; humanes biologisches Herzunterstützungsystem (hBioVad); pulsatile Dehnung; IGF-1; paraBioVAD
 

Statistik

Publish here

Browse

All of eDissFaculties & ProgramsIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesTypeThis FacultyIssue DateAuthorAdvisor & RefereeAdvisorRefereeTitlesType

Help & Info

Publishing on eDissPDF GuideTerms of ContractFAQ

Contact Us | Impressum | Cookie Consents | Data Protection Information
eDiss Office - SUB Göttingen (Central Library)
Platz der Göttinger Sieben 1
Mo - Fr 10:00 – 12:00 h


Tel.: +49 (0)551 39-27809 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
ediss_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]
Göttingen State and University Library | Göttingen University
Medicine Library (Doctoral candidates of medicine only)
Robert-Koch-Str. 40
Mon – Fri 8:00 – 24:00 h
Sat - Sun 8:00 – 22:00 h
Holidays 10:00 – 20:00 h
Tel.: +49 551 39-8395 (general inquiries)
Tel.: +49 (0)551 39-28655 (open access/parallel publications)
bbmed_AT_sub.uni-goettingen.de
[Please replace "_AT_" with the "@" sign when using our email adresses.]