Cardiac preservation using ex vivo organ perfusion: new therapies for the treatment of heart failure by harnessing the power of growth factors using BMP mimetics like THR-184.

IF 2.8 3区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS
Frontiers in Cardiovascular Medicine Pub Date : 2025-03-18 eCollection Date: 2025-01-01 DOI:10.3389/fcvm.2025.1535778
William D Carlson, Dattatreyamurty Bosukonda, Peter C Keck, Philippe Bey, Shannon N Tessier, Frederic R Carlson
{"title":"Cardiac preservation using <i>ex vivo</i> organ perfusion: new therapies for the treatment of heart failure by harnessing the power of growth factors using BMP mimetics like THR-184.","authors":"William D Carlson, Dattatreyamurty Bosukonda, Peter C Keck, Philippe Bey, Shannon N Tessier, Frederic R Carlson","doi":"10.3389/fcvm.2025.1535778","DOIUrl":null,"url":null,"abstract":"<p><p>As heart transplantation continues to be the gold standard therapy for end-stage heart failure, the imbalance between the supply of hearts, and the demand for them, continues to get worse. In the US alone, with less than 4,000 hearts suitable for transplant and over 100,000 potential recipients, this therapy is only available to a very few. The use of hearts Donated after Circulatory Death (DCD) and Donation after Brain Death (DBD) using <i>ex vivo</i> machine perfusion (EVMP) is a promising approach that has already increased the availability of suitable organs for heart transplantation. EVMP offers the promise of enabling the expansion of the overall number of heart transplants and lower rates of early graft dysfunction. These are realized through (1) safe extension of the time between procurement and transplantation and (2) <i>ex vivo</i> assessment of preserved hearts. Notably, <i>ex vivo</i> perfusion has facilitated the donation of DCD hearts and improved the success of transplantation. Nevertheless, DCD hearts suffer from serious preharvest ischemia/reperfusion injury (IRI). Despite these developments, only 40% of hearts offered for transplantation can be utilized. These devices do offer an opportunity to evaluate donor hearts for transplantation, resuscitate organs previously deemed unsuitable for transplantation, and provide a platform for the development of novel therapeutics to limit cardiac injury. Bone Morphogenetic Protein (BMP) signaling is a new target which holds the potential for ameliorating myocardial IRI. Recent studies have demonstrated that BMP signaling has a significant role in blocking the deleterious effects of injury to the heart. We have designed novel small peptide BMP mimetics that act via activin receptor-like kinase (ALK3), a type I BMP receptor. They are capable of (1) inhibiting inflammation and apoptosis, (2) blocking/reversing the epithelial-mesenchymal transition (EMT) and fibrosis, and (3) promoting tissue regeneration. In this review, we explore the promise that novel therapeutics, including these BMP mimetics, offer for the protection of hearts against myocardial injury during <i>ex vivo</i> transportation for cardiac transplantation. This protection represents a significant advance and a promising <i>ex vivo</i> therapeutic approach to expanding the donor pool by increasing the number of transplantable hearts.</p>","PeriodicalId":12414,"journal":{"name":"Frontiers in Cardiovascular Medicine","volume":"12 ","pages":"1535778"},"PeriodicalIF":2.8000,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11960666/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Cardiovascular Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fcvm.2025.1535778","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}
引用次数: 0

Abstract

As heart transplantation continues to be the gold standard therapy for end-stage heart failure, the imbalance between the supply of hearts, and the demand for them, continues to get worse. In the US alone, with less than 4,000 hearts suitable for transplant and over 100,000 potential recipients, this therapy is only available to a very few. The use of hearts Donated after Circulatory Death (DCD) and Donation after Brain Death (DBD) using ex vivo machine perfusion (EVMP) is a promising approach that has already increased the availability of suitable organs for heart transplantation. EVMP offers the promise of enabling the expansion of the overall number of heart transplants and lower rates of early graft dysfunction. These are realized through (1) safe extension of the time between procurement and transplantation and (2) ex vivo assessment of preserved hearts. Notably, ex vivo perfusion has facilitated the donation of DCD hearts and improved the success of transplantation. Nevertheless, DCD hearts suffer from serious preharvest ischemia/reperfusion injury (IRI). Despite these developments, only 40% of hearts offered for transplantation can be utilized. These devices do offer an opportunity to evaluate donor hearts for transplantation, resuscitate organs previously deemed unsuitable for transplantation, and provide a platform for the development of novel therapeutics to limit cardiac injury. Bone Morphogenetic Protein (BMP) signaling is a new target which holds the potential for ameliorating myocardial IRI. Recent studies have demonstrated that BMP signaling has a significant role in blocking the deleterious effects of injury to the heart. We have designed novel small peptide BMP mimetics that act via activin receptor-like kinase (ALK3), a type I BMP receptor. They are capable of (1) inhibiting inflammation and apoptosis, (2) blocking/reversing the epithelial-mesenchymal transition (EMT) and fibrosis, and (3) promoting tissue regeneration. In this review, we explore the promise that novel therapeutics, including these BMP mimetics, offer for the protection of hearts against myocardial injury during ex vivo transportation for cardiac transplantation. This protection represents a significant advance and a promising ex vivo therapeutic approach to expanding the donor pool by increasing the number of transplantable hearts.

求助全文
约1分钟内获得全文 求助全文
来源期刊
Frontiers in Cardiovascular Medicine
Frontiers in Cardiovascular Medicine Medicine-Cardiology and Cardiovascular Medicine
CiteScore
3.80
自引率
11.10%
发文量
3529
审稿时长
14 weeks
期刊介绍: Frontiers? Which frontiers? Where exactly are the frontiers of cardiovascular medicine? And who should be defining these frontiers? At Frontiers in Cardiovascular Medicine we believe it is worth being curious to foresee and explore beyond the current frontiers. In other words, we would like, through the articles published by our community journal Frontiers in Cardiovascular Medicine, to anticipate the future of cardiovascular medicine, and thus better prevent cardiovascular disorders and improve therapeutic options and outcomes of our patients.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信