Our publication (review) on “direct cardiogenesis” strategies for heart regeneration is online!

Is it possible to reawaken the intrinsic cardiac regenerative potential after major injuries, for example induced by myocardial infarction? We are happy to share our publication (review) on an emerging, promising and rapidly evolving approach for heart regeneration based on stimulating the proliferation of endogenous cardiac muscle cells.

Abstract:  Despite considerable efforts carried out to develop stem/progenitor cell-based technologies aiming at replacing and restoring the cardiac tissue following severe damages, thus far no strategies based on adult stem cell transplantation have been demonstrated to efficiently generate new cardiac muscle cells. Intriguingly, dedifferentiation, and proliferation of pre-existing cardiomyocytes and not stem cell differentiation represent the preponderant cellular mechanism by which lower vertebrates spontaneously regenerate the injured heart. Mammals can also regenerate their heart up to the early neonatal period, even in this case by activating the proliferation of endogenous cardiomyocytes. However, the mammalian cardiac regenerative potential is dramatically reduced soon after birth, when most cardiomyocytes exit from the cell cycle, undergo further maturation, and continue to grow in size. Although a slow rate of cardiomyocyte turnover has also been documented in adult mammals, both in mice and humans, this is not enough to sustain a robust regenerative process. Nevertheless, these remarkable findings opened the door to a branch of novel regenerative approaches aiming at reactivating the endogenous cardiac regenerative potential by triggering a partial dedifferentiation process and cell cycle re-entry in endogenous cardiomyocytes. Several adaptations from intrauterine to extrauterine life starting at birth and continuing in the immediate neonatal period concur to the loss of the mammalian cardiac regenerative ability. A wide range of systemic and microenvironmental factors or cell-intrinsic molecular players proved to regulate cardiomyocyte proliferation and their manipulation has been explored as a therapeutic strategy to boost cardiac function after injuries. We here review the scientific knowledge gained thus far in this novel and flourishing field of research, elucidating the key biological and molecular mechanisms whose modulation may represent a viable approach for regenerating the human damaged myocardium.

Go to the full article: : Bongiovanni C, Sacchi F, Da Pra S, Pantano E, Miano C, Morelli MB and D’Uva G. Reawakening the intrinsic cardiac regenerative potential: molecular strategies to boost dedifferentiation and proliferation of endogenous cardiomyocytes. Frontiers in Cardiovascular Medicine – Cardiovascular Biologics and Regenerative Medicine, 2021

#research #heart #regeneration #cardiomyocyte #proliferation #myocardialinfarction #duvalab

Our article on heart regeneration is out in Stem Cell Reports!

Happy to have collaborated to this international project on mammalian heart regeneration! Congratulations to Diana Nascimento and her team!

Abstract: So far, opposing outcomes have been reported following neonatal apex resection in mice, questioning the validity of this injury model to investigate regenerative mechanisms. We performed a systematic evaluation, up to 180 days after surgery, of the pathophysiological events activated upon apex resection. In response to cardiac injury, we observed increased cardiomyocyte proliferation in remote and apex regions, neovascularization, and local fibrosis. In adulthood, resected hearts remain consistently shorter and display permanent fibrotic tissue deposition in the center of the resection plane, indicating limited apex regrowth. However, thickening of the left ventricle wall, explained by an upsurge in cardiomyocyte proliferation during the initial response to injury, compensated cardiomyocyte loss and supported normal systolic function. Thus, apex resection triggers both regenerative and reparative mechanisms, endorsing this injury model for studies aimed at promoting cardiomyocyte proliferation and/or downplaying fibrosis.

Go to the full article: Sampaio-Pinto V, Rodrigues S, Laúndos T, Silva E, Nóvoa F, Silva A, Cerqueira R, Resende T, Pianca N, Leite-Moreira A, D’Uva G, Thorsteinsdóttir S, Pinto-do-Ó P, Nascimento DS. Neonatal Apex Resection Triggers Cardiomyocyte Proliferation, Neovascularization and Functional Recovery Despite Local Fibrosis. Stem Cell Report, 2018

Symposium on heart regeneration 2017

We are organizing a “Symposium on heart regeneration: Direct stimulation of cardiogenesis as a novel strategy for treating heart failure”. The meeting will be held at our institution (Scientific and Technological Pole, IRCCS MultiMedica, Italy) on November 16th 2017. Invited speakers include our collaborators and international leaders in heart regeneration, namely Prof. E.Tzahor (Weizmann Institute, Israel), Prof. J.Bakkers (Hubrecht Institute, The Netherlands) and Prof. Gilbert Weidinger (Ulm University, Germany).

Our editorial article on cardiac regeneration is out in Cell Cycle!

Heart injuries such as those induced by acute ischemia can lead to heart failure, the most common cardiac ailment and a serious health problem worldwide. This occurs mainly due to the inability of the mammalian heart to regenerate after injury. Developing strategies to boost cardiac regeneration processes in humans is therefore clinically imperative.

Go to the full article: D’Uva G and Tzahor E. The key roles of ERBB2 in cardiac regeneration. Cell Cycle, 2015

Our article on heart regeneration is out in Nature Cell Biology!

The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 ( NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages. Induction of a constitutively active ERBB2 (ca ERBB2) in neonatal, juvenile and adult CMs resulted in cardiomegaly, characterized by extensive CM hypertrophy, dedifferentiation and proliferation, differentially mediated by ERK, AKT and GSK3β/ β-catenin signalling pathways. Transient induction of ca ERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.

Go to the full article: Gabriele D’Uva, Alla Aharonov, Mattia Lauriola, David Kain, Yfat Yahalom-Ronen, Silvia Carvalho, Karen Weisinger, Elad Bassat, Dana Rajchman, Oren Yifa, Marina Lysenko, Tal Konfino, Julius Hegesh, Ori Brenner, Michal Neeman, Yosef Yarden, Jonathan Leor, Rachel Sarig, Richard P Harvey and Eldad Tzahor. ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nature Cell Biology, 2015

Scientific recognitions

MEDIA COVERAGE

06.04.2015 – The Guardian: Heart muscle cells regrown in medical research breakthrough


06.04.2015 – The Sydney Morning Herald: Australian researchers help find way to regrow heart muscle


07.04.2015 – RT: Scientists discover revolutionary method to regrow heart muscles


07.04.2015 – AM: Helping the heart repair itself after a cardiac arrest: researchers say they’ve worked out how


07.04.2015 – Financial Express: The Turbo-charging hormone can repair ‘broken’ heart


07.04.2015 – El Comercio: Logran regenerar músculos del corazón al estimular una hormona


07.04.2015 – SKY NEWS: Breakthrough Sees Heart Muscle Cells Regrown


07.04.2015 – SBS: Scientific breakthrough could give new hope to heart-attack patients


07.04.2015 – The Jewish Press: Israeli-Australian Researchers Discover How to Regrow Heart Muscle


07.04.2015 – Business Magazin: STUDIU: Cercetătorii au reuşit să stimuleze regenerarea celulelor muşchiului cardiac


07.04.2015 – iarul de Iasi: Cercetătorii au reuşit să stimuleze regenerarea celulelor muşchiului cardiac


07.04.2015 – ZeeNews: Scientists regenerate cardiac muscles through hormone stimulation


07.04.2015 – Medical Xpress: Research effort leads to mammalian heart tissue regeneration


07.04.2015 – Kurier: Durchbruch: Forscher lassen Herzmuskelzellen wachsen


08.04.2015 – SBS World NEWS: Researchers Trigger Heart Regeneration After Heart Attack (TV news)


08.04.2015 – The Times of Israel: Medical leap as Israeli researchers regrow heart cells


08.04.2015 – smarTherapy: Consiguen regenerar los músculos del corazón mediante estimulación hormonal


08.04.2015 – Scimondo: Aktivierung eines Hormon-Signalweges hilft Mäuseherzen nach einem Herzinfarkt auf die Sprünge


08.04.2015 – Beyond the Dish: Dead Heart Muscle Regrown in Rodents


08.04.2015 – Phys.org: Research finds turbo-charging hormone can regrow the heart


08.04.2015 – Newsmax: Hormone Found to Regenerate Heart Muscle


09.04.2015 – Medical Daily: Heart Attack Patients May Regrow Cardiac Cells By 2020 Thanks To Breakthrough Discovery


09.04.2015 – The Australian: Bashing corporate Australia has reunited the faceless man with his Green frenemies


10.04.2015 – SILICONWADI: Ricercatori israeliani fanno ricrescere le cellule del cuore


10.04.2015 – Italiasalute.it: Nuova tecnica per curare il cuore infartuato


10.04.2015 – Tiscali: Cuore infartuato, scoperto il meccanismo che avvia la formazione di nuove cellule


10.04.2015 – Ansa: Scoperta la chiave per riparare il cuore infartuato


10.04.2015 – MeteoWeb.eu: Salute: scoperta la chiave per riparare il cuore infartuato


10.04.2015 – Bionn: 拯救心脏 拒绝梗死! – 大健康产业专区- 生物谷


11.04.2015 – Giornale di Sicilia: Cuore colpito da infarto, scoperta la chiave per ripararlo


12.04.2015 – Il Quotidiano di Puglia: Con questo gene riparerò il cuore


12.04.2015 – NurseTimes: Scoperta la chiave per riparare il tessuto cardiaco infartuato


13.04.2015 – Il Sole 24 Ore: Cuore, identificato gene capace di “ripararlo”


13.04.2015 – HealthCanal: Heart Cells Regenerated in Mice


13.04.2015 – IBA: הלב את מחדשים


13.04.2015 – Radio Jai: Científicos de Israel regeneran células del corazón de ratones


13.04.2015 – EnlaceJudío: Científicos israelíes regeneran células cardíacas


13.04.2015 – israel21c: Weizmann Institute scientists regenerate heart cells in mice


13.04.2015 – IsraCast: Medical Breakthrough – Israeli Scientists Find Way to Regrow Heart Muscle Cells


13.04.2015 – Science Daily: Heart cells regenerated in mice


13.04.2015 – Popular Science: Scoperta la chiave per riparare il cuore infartuato


13.04.2015 – Science Codex: Heart cells regenerated in mice in NGR1 study


13.04.2015 – Science 2.0: Heart Cells Regenerated By Going Backward To Make Progress


13.04.2015 – ScienceBlogs – The Weizmann Wave: Guest post: Dr. Gabriele D’Uva: How to Grow New Heart Cells


13.04.2015 – Il Resto del Carlino: Nuove cellule grazie alla ricerca. Così si ripara il cuore infartuato


14.04.2015 – The Jerusalem Post: Weizmann Institute researchers regenerate heart cells in mice


14.04.2015 – Farmacia.it: Lotta all’infarto: il cuore potrà essere riparato


14.04.2015 – ANI News: Regeneration of heart cells possible in mice


14.04.2015 – Business Standard: Regeneration of heart cells possible in mice


14.04.2015 – New Kerala: Regeneration of heart cells possible in mice


14.04.2015 – Corriere del mezzogiorno: Studio il cuore, sogno l’Italia


14.04.2015 – Israel Hayom: Israeli scientists make revolutionary discovery, regenerate heart cells


14.04.2015 – Genetic Engeneering & Biotechnology News: Old Heart Cells Divide Like New


14.04.2015 – Daily News & Analysis: Scientists regenerate heart cells in mice


14.04.2015 – Cardiovascular Disease News: Study Advances Understanding of Heart Cells’ Regeneration


14.04.2015 – Comité Central Israelita Uruguay: Científicos israelíes regeneran células cardíacas


14.04.2015 – Prahova: Cercetatorii au reusit sa stimuleze regenerarea celulelor muschiului cardiac


14.04.2015 – Iran Daily: Heart cells regenerated in mice


14.04.2015 – Horizon 2020 projects: ERC-funded research sees mouse heart cells renewed


14.04.2015 – Israeli Ministry of Foreign Affairs: Heart cells regenerated in mice


14.04.2015 – MedIndia: Regeneration of Heart Cells Possible in Mice With the Help of Specialized Protein, ERBB2


14.04.2015 – DAILYROUNDS: Successful heart muscle regeneration in mice may soon be seen in humans


14.04.2015 – Jns: Israeli Scientists Regenerate Heart Cells in Revolutionary Discovery


15.04.2015 – The Algemeiner: Israeli Scientists Regenerate Heart Cells in Revolutionary Discovery


15.04.2015 – Nature子刊:ERBB2触发哺乳动物心脏再生是通过促进心肌细胞去分化和增殖


15.04.2015 – Sanità Salento: Un cuore rigenerato per gli infartuati (con intervista radiofonica)


15.04.2015 – Medical Insider: Ученые научились восстанавливать сердечную мышцу


16.04.2015 – Diario del web: Scienziati rigenerano le cellule del cuore


17.04.2015 – Innovations Report: Weizmann Institute Scientists Regenerate Heart Cells in Mice


18.04.2015 – Globus Magazine: RIGENERAZIONE CARDIACA: TROVATA LA CHIAVE PER RIPARARE IL CUORE INFARTUATO


19.04.2015 – Ultime Tecno-scientifiche: COSI’ SI RIPARA IL CUORE INFARTUATO


19.04.2015 – Corriere di Bologna: Gabriele, il ricercatore che ha riacceso il cuore e vuol tornare in Italia


20.04.2015 – Giannella channel: È italiano il medico che ha scoperto come riparare un cuore infranto


20.04.2015 – PolskieRadio: Komórki serca potrafią się zregenerować po zawale


21.04.2015 – multibriefs: Researchers regenerate heart cells in mice


23.04.2015 – UNIBO MAGAZINES: Ecco il gene chiave per riparare il cuore dopo un infarto


23.04.2015 – UNI news24: ERBB2: scoperto il gene che rigenera il cuore dopo un infarto


23.04.2015 – La Repubblica: Trovato un gene per riparare il cuore dopo un infarto


23.04.2015 – RaiNews: Un gene ripara-cuore


23.04.2015 – Rai3 – TGR Emilia Romagna (TV news – min. 15:34)


23.04.2015 – Bologna2000.it: Identificato un gene chiave capace di riparare il cuore danneggiato da un infarto


23.04.2015 – SassuoloOnline: Identificato un gene chiave capace di riparare il cuore danneggiato da un infarto


23.04.2015 – L’Adige: Scoperto gene per riparare il cuore dopo l’infarto

23.04.2015 – Controcampus.it: Gene chiave salva il cuore dopo un infarto, ricerca Unibo


23.04.2015 – Virgilio Notizie: Scoperto un gene per riparare il cuore dopo un infarto


23.04.2015 – TRC: Post infarto, importante scoperta medica


23.04.2015 – AGI: Ricerca Unibo: identificato gene per riparare cuore dopo infarto


23.04.2015 – BolognaToday: Ricerca Unibo: scoperto gene chiave per riparare il cuore dopo un infarto


27.04.2015 – Viversani: Scoperto un gene per riparare il cuore dopo un infarto


27.04.2015 – ResearchItaly: Identified the gene that can repair the heart after a heart attack


27.04.2015 – Biotechin: A “Hearty” discovery – Turbo-charging hormone can regrow the heart


28.04.2015 – Salzburger Nachrichten: Krebs-Wachstumsrezeptor steuert Regeneration von Herzzellen


29.04.2015 – HealthCanal: HEART ATTACK BREAKTHROUGH


02.05.2015 – LiveUniversity: Scoperto gene chiave capace di riparare il cuore danneggiato da un infarto


06.05.2015 – The Australian Jewish News: A heartening collaboration


06.05.2015 – Iton Gadol: Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments


06.05.2015 – AJN: Avances. Investigadores israelíes regeneran células del corazón para tratar la enfermedad cardiac


06.05.2015 – NoCamels: Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments


06.05.2015 – vetscite.org: Heart cells regenerated in mice


07.05.2015 – Yad be Yad: Investigadores israelíes regeneran células del corazón para tratar enfermedades cardíacas


08.05.2015 – Classic Chaos: Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments


14.05.2015 – VitAssistance: Cuore, identificato gene capace di ripararlo


6.06.2015 – Ruthfully yours: Amazing Israel :Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments