Bioartificial heart - Revision history

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	A '''bioartificial heart''' is an engineered [[heart]] that contains the [[extracellular matrix\|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">{{~~cite journal\|last1=Ott\|first1=Harald C~~\|~~last2=Matthiesen\|first2=Thomas S\|last3=Goh\|first3=Saik-Kia\|last4=Black\|first4=Lauren D\|last5=Kren\|first5=Stefan M\|last6=Netoff\|first6=Theoden I\|last7=Taylor\|first7=Doris~~ A~~\|title=Perfusion-decellularized matrix: using nature's platform~~ to ~~engineer~~ a ~~bioartificial~~ heart\|journal=Nature Medicine\|date=13 January 2008\|volume=14\|issue=2\|pages=213–221\|doi=10.1038/nm1684\|pmid=18193059}}</ref><ref name="Song">{{cite journal\|last1=Song\|first1=Jeremy J.\|last2=Ott\|first2=Harald C.\|title=Organ engineering based on decellularized matrix scaffolds\|journal=Trends in Molecular Medicine\|date=August 2011\|volume=17\|issue=8\|pages=424–432\|doi=10.1016/j.molmed.2011.03.005}}</ref><ref>{{cite news\|last1=Highfield\|first1=Roger\|title=First bioartificial heart may signal end of organ shortage\|url=https://www.telegraph.co.uk/news/science/science-news/3321616/First-bioartificial-heart-may-signal-end-of-organ-shortage.html\|accessdate=February 10, 2016\|work=The Telegraph\|date=January 13, 2008}}</ref> In 2014, human-sized bioartificial pig hearts were constructed.<ref name="Weymann">{{cite journal\|last1=Weymann\|first1=Alexander\|last2=Patil\|first2=Nikhil Prakash\|last3=Sabashnikov\|first3=Anton\|last4=Jungebluth\|first4=Philipp\|last5=Korkmaz\|first5=Sevil\|last6=Li\|first6=Shiliang\|last7=Veres\|first7=Gabor\|last8=Soos\|first8=Pal\|last9=Ishtok\|first9=Roland\|last10=Chaimow\|first10=Nicole\|last11=Pätzold\|first11=Ines\|last12=Czerny\|first12=Natalie\|last13=Schies\|first13=Carsten\|last14=Schmack\|first14=Bastian\|last15=Popov\|first15=Aron-Frederik\|last16=Simon\|first16=André Rüdiger\|last17=Karck\|first17=Matthias\|last18=Szabo\|first18=Gabor\|last19=Benedetto\|first19=Umberto\|title=Bioartificial Heart: A Human-Sized Porcine Model – The Way Ahead\|journal=PLoS ONE\|date=3 November 2014\|volume=9\|issue=11\|pages=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">{{cite journal\|last1=Gálvez-Montón\|first1=Carolina\|last2=Prat-Vidal\|first2=Cristina\|last3=Roura\|first3=Santiago\|last4=Soler-Botija\|first4=Carolina\|last5=Bayes-Genis\|first5=Antoni\|title=Cardiac Tissue Engineering and the Bioartificial Heart\|journal=Revista Española de Cardiología (English Edition)\|date=May 2013\|volume=66\|issue=5\|pages=391–399\|doi=10.1016/j.rec.2012.11.012}}~~</ref>~~		{{Short description\|A bioengineered organ designed to replace a failing human heart}}

	==~~Background~~==		==Bioartificial heart==
	~~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 />~~		A '''bioartificial heart''' is an advanced [[bioengineering]] construct designed to replace a failing [[human heart]]. It combines [[biological]] and [[synthetic]] materials to create a functional organ that can be transplanted into patients with severe [[heart disease]]. The development of bioartificial hearts is a part of the broader field of [[tissue engineering]] and regenerative medicine.

	== ~~Methodology~~ ==		==Development==
	~~{{Main article\|Decellularization}}~~		The creation of a bioartificial heart involves several key steps:
	The ~~preferred method to remove all cellular components from~~ a heart ~~is perfusion decellularization. This technique~~ involves ~~perfusing the heart with [[SDS (chemical)\|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>{{cite journal\|last1=Traphagen\|first1=S\|last2=Yelick\|first2=PC\|title=Reclaiming a natural beauty: whole-organ engineering with natural extracellular materials.\|journal=Regenerative Medicine\|date=September 2009\|volume=4\|issue=5\|pages=747–58\|pmid=19761399\|doi=10.~~2217/rme.09.38\|pmc=3021746}}</ref>~~		===Decellularization===
			The process begins with the decellularization of a donor heart, which involves removing all the [[cells]] from the heart tissue, leaving behind a [[scaffold]] of [[extracellular matrix]]. This scaffold retains the complex architecture of the heart, including its [[valves]], [[chambers]], and [[blood vessels]].

	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>{{cite journal\|last1=Laflamme\|first1=Michael A\|last2=Murry\|first2=Charles E\|title=Regenerating~~ the ~~heart\|journal=Nature Biotechnology\|date=July 2005\|volume=23\|issue=7\|pages=845–856\|doi=10~~.~~1038/nbt1117\|pmid=16003373}}</ref>~~		===Recellularization===
			Once the scaffold is prepared, it is recellularized with [[stem cells]] or [[progenitor cells]] that can differentiate into the various cell types needed to form a functional heart. These cells are often derived from the patient's own [[induced pluripotent stem cells]] (iPSCs) to reduce the risk of [[immune rejection]].

	== ~~Recellularized heart functionality~~ ==		===Bioreactor Cultivation===
	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 />~~		The recellularized scaffold is then placed in a [[bioreactor]], a device that provides the necessary [[nutrients]], [[oxygen]], and [[mechanical stimulation]] to promote cell growth and maturation. The bioreactor mimics the physiological conditions of the human body, allowing the cells to develop into a functional heart tissue.

	~~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.		==Challenges==
			The development of bioartificial hearts faces several challenges:

	~~== References ==~~		* '''Vascularization''': Ensuring adequate blood supply to the growing tissue is critical. Researchers are working on techniques to promote the formation of [[blood vessels]] within the scaffold.
	~~{{reflist\|30em}}~~		* '''Functional Integration''': The bioartificial heart must integrate seamlessly with the patient's [[circulatory system]] and function in synchrony with the body's [[electrical signals]].
			* '''Longevity and Durability''': The engineered heart must withstand the mechanical stresses of continuous [[pumping]] over a long period.

			==Potential Benefits==
			Bioartificial hearts offer several potential benefits over traditional [[heart transplants]]:

			* '''Reduced Rejection''': Using the patient's own cells minimizes the risk of [[immune rejection]].
			* '''Increased Availability''': Bioartificial hearts could alleviate the shortage of donor hearts.
			* '''Personalization''': The ability to tailor the heart to the patient's specific needs and [[genetic makeup]].

			==Current Research==
			Research in the field of bioartificial hearts is ongoing, with several promising developments:

			* '''3D Bioprinting''': Advances in [[3D printing]] technology are enabling the precise construction of heart tissues with complex structures.
			* '''Gene Editing''': Techniques like [[CRISPR]] are being explored to enhance the functionality and compatibility of the cells used in bioartificial hearts.
			* '''Clinical Trials''': Some bioartificial heart prototypes are entering early-stage [[clinical trials]] to assess their safety and efficacy in humans.

			==Related pages==
			* [[Heart transplant]]
			* [[Tissue engineering]]
			* [[Regenerative medicine]]
			* [[Stem cell therapy]]

			[[Category:Bioengineering]]
	[[Category:Cardiology]]		[[Category:Cardiology]]
	[[Category:Tissue engineering]]		[[Category:Tissue engineering]]
	~~{{dictionary-stub1}}~~

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A '''bioartificial heart''' is an engineered [[heart]] that contains the [[extracellular matrix|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">{{cite journal|last1=Ott|first1=Harald C|last2=Matthiesen|first2=Thomas S|last3=Goh|first3=Saik-Kia|last4=Black|first4=Lauren D|last5=Kren|first5=Stefan M|last6=Netoff|first6=Theoden I|last7=Taylor|first7=Doris A|title=Perfusion-decellularized matrix: using nature's platform to engineer a bioartificial heart|journal=Nature Medicine|date=13 January 2008|volume=14|issue=2|pages=213–221|doi=10.1038/nm1684|pmid=18193059}}</ref><ref name="Song">{{cite journal|last1=Song|first1=Jeremy J.|last2=Ott|first2=Harald C.|title=Organ engineering based on decellularized matrix scaffolds|journal=Trends in Molecular Medicine|date=August 2011|volume=17|issue=8|pages=424–432|doi=10.1016/j.molmed.2011.03.005}}</ref><ref>{{cite news|last1=Highfield|first1=Roger|title=First bioartificial heart may signal end of organ shortage|url=https://www.telegraph.co.uk/news/science/science-news/3321616/First-bioartificial-heart-may-signal-end-of-organ-shortage.html|accessdate=February 10, 2016|work=The Telegraph|date=January 13, 2008}}</ref> In 2014, human-sized bioartificial pig hearts were constructed.<ref name="Weymann">{{cite journal|last1=Weymann|first1=Alexander|last2=Patil|first2=Nikhil Prakash|last3=Sabashnikov|first3=Anton|last4=Jungebluth|first4=Philipp|last5=Korkmaz|first5=Sevil|last6=Li|first6=Shiliang|last7=Veres|first7=Gabor|last8=Soos|first8=Pal|last9=Ishtok|first9=Roland|last10=Chaimow|first10=Nicole|last11=Pätzold|first11=Ines|last12=Czerny|first12=Natalie|last13=Schies|first13=Carsten|last14=Schmack|first14=Bastian|last15=Popov|first15=Aron-Frederik|last16=Simon|first16=André Rüdiger|last17=Karck|first17=Matthias|last18=Szabo|first18=Gabor|last19=Benedetto|first19=Umberto|title=Bioartificial Heart: A Human-Sized Porcine Model – The Way Ahead|journal=PLoS ONE|date=3 November 2014|volume=9|issue=11|pages=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">{{cite journal|last1=Gálvez-Montón|first1=Carolina|last2=Prat-Vidal|first2=Cristina|last3=Roura|first3=Santiago|last4=Soler-Botija|first4=Carolina|last5=Bayes-Genis|first5=Antoni|title=Cardiac Tissue Engineering and the Bioartificial Heart|journal=Revista Española de Cardiología (English Edition)|date=May 2013|volume=66|issue=5|pages=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 (chemical)|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>{{cite journal|last1=Traphagen|first1=S|last2=Yelick|first2=PC|title=Reclaiming a natural beauty: whole-organ engineering with natural extracellular materials.|journal=Regenerative Medicine|date=September 2009|volume=4|issue=5|pages=747–58|pmid=19761399|doi=10.2217/rme.09.38|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>{{cite journal|last1=Laflamme|first1=Michael A|last2=Murry|first2=Charles E|title=Regenerating the heart|journal=Nature Biotechnology|date=July 2005|volume=23|issue=7|pages=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 ==
{{reflist|30em}}

[[Category:Cardiology]]
[[Category:Tissue engineering]]
{{dictionary-stub1}}