Bioartificial heart

A bioartificial heart is an engineered heart that contains the extracellular structure of a decellularized heart and cellular components from a different source. Such hearts are of particular interest for therapy as well as research into heart disease. The first bioartificial hearts were created in 2008 using cadaveric rat hearts.<ref name="Ott">,

 Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart, 
 Nature Medicine, 
 
 Vol. 14(Issue: 2),
 pp. 213–221,
 DOI: 10.1038/nm1684,
 PMID: 18193059,</ref><ref name="Song">, 
 Organ engineering based on decellularized matrix scaffolds, 
 Trends in Molecular Medicine, 
 
 Vol. 17(Issue: 8),
 pp. 424–432,
 DOI: 10.1016/j.molmed.2011.03.005,</ref><ref>

,

 First bioartificial heart may signal end of organ shortage Full text, 
 The Telegraph, 
  
 January 13, 2008,

</ref> In 2014, human-sized bioartificial pig hearts were constructed.<ref name="Weymann">,

 Bioartificial Heart: A Human-Sized Porcine Model – The Way Ahead, 
 PLoS ONE, 
 
 Vol. 9(Issue: 11),
 pp. e111591,
 DOI: 10.1371/journal.pone.0111591,
 PMID: 25365554,
 PMC: 4218780,</ref> Bioartificial hearts have not been developed yet for clinical use, although the recellularization of porcine hearts with human cells opens the door to xenotransplantation.<ref name="Weymann" /><ref name="Galvez">, 
 Cardiac Tissue Engineering and the Bioartificial Heart, 
 Revista Española de Cardiología (English Edition), 
 
 Vol. 66(Issue: 5),
 pp. 391–399,
 DOI: 10.1016/j.rec.2012.11.012,</ref>

Background

Heart failure is one of the leading causes of death. Often, the only viable treatment for end-stage heart failure is organ transplantation.<ref name=Galvez /> Currently organ supply is insufficient to meet the demand, which presents a large limitation in an end-stage treatment plan.<ref name=Song /><ref name=Galvez /> A theoretical alternative to traditional transplantation processes is the engineering of personalized bioartificial hearts. Researchers have had many successful advances in the engineering of cardiovascular tissue and have looked towards using decellularized and recellularized cadaveric hearts in order to create a functional organ.<ref name=Galvez /> Decellularization-recellularization involves using a cadaveric heart, removing the cellular contents while maintaining the protein matrix (decellularization), and subsequently facilitating growth of appropriate cardiovascular tissue inside the remaining matrix (recellularization).<ref name=Galvez />

Methodology

Main article: Decellularization

The preferred method to remove all cellular components from a heart is perfusion decellularization. This technique involves perfusing the heart with SDS, distilled water and Triton X-100.<ref name="Ott" />

The remaining ECM is composed of structural elements such as collagen, laminin, elastin and fibronectin. The ECM scaffold promotes proper cellular proliferation and differentiation, vascular development, as well as providing mechanical support for cellular growth.<ref name=Galvez /> Because minimal DNA material remains after the decellularization process, the engineered organ is biocompatible with the transplant recipient, regardless of species. Unlike traditional transplant options, recellularized hearts are less immunogenic and have a decreased risk of rejection.<ref name=Song /><ref name=Traphagen>,

 Reclaiming a natural beauty: whole-organ engineering with natural extracellular materials., 
 Regenerative Medicine, 
 
 Vol. 4(Issue: 5),
 pp. 747–58,
 DOI: 10.2217/rme.09.38,
 PMID: 19761399,
 PMC: 3021746,</ref>

Once the decellularized heart has been sterilized to remove any pathogens, the recellularization process can occur.<ref name=Song /> These MCPs are then added to the decellularized heart and with additional exogenous growth factors, are stimulated to differentiate into cardiomyocytes, smooth muscle cells and endothelial cells.<ref name=Laflamme>,

 Regenerating the heart, 
 Nature Biotechnology, 
 
 Vol. 23(Issue: 7),
 pp. 845–856,
 DOI: 10.1038/nbt1117,
 PMID: 16003373,</ref>

Recellularized heart functionality

The most promising results come from recellularized rat hearts. After only 8 days of maturation, the heart models were stimulated with an electrical signal to provide pacing. The heart models showed a unified contraction with a force equivalent to ~2% of a normal rat heart or ~25% of that of a 16-week-old human heart.<ref name="Ott" /><ref name=Galvez />

Although far from use in a clinical setting, there have been great advances in the field of bioartificial heart generation.<ref name=Song /><ref name=Galvez /><ref name=Laflamme /> The use of decellularization and recellularization processes, has led to the production of a three dimensional matrix that promotes cellular growth; the repopulation of the matrix containing appropriate cell composition; and the bioengineering of organs demonstrating functionality (limited) and responsiveness to stimuli.<ref name=Song /><ref name=Galvez /> This area shows immense promise and with future research may redefine treatment of end stage heart failure.

References

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