Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors.

Autor: Poch CM; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Foo KS; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden.; Department of Medicine, Karolinska Institutet, Huddinge, Sweden., De Angelis MT; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Institute of Regenerative Medicine in Cardiology, Technical University of Munich, Munich, Germany., Jennbacken K; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Santamaria G; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Institute of Regenerative Medicine in Cardiology, Technical University of Munich, Munich, Germany., Bähr A; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Wang QD; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Reiter F; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Hornaschewitz N; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Zawada D; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Institute of Regenerative Medicine in Cardiology, Technical University of Munich, Munich, Germany., Bozoglu T; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., My I; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Meier A; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Institute of Regenerative Medicine in Cardiology, Technical University of Munich, Munich, Germany., Dorn T; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Institute of Regenerative Medicine in Cardiology, Technical University of Munich, Munich, Germany., Hege S; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Lehtinen ML; Department of Medicine, Karolinska Institutet, Huddinge, Sweden., Tsoi YL; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Hovdal D; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden., Hyllner J; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.; Division of Biotechnology, IFM, Linköping University, Linköping, Sweden., Schwarz S; Center for Applied Tissue Engineering and Regenerative Medicine (CANTER), Munich University of Applied Sciences, Munich, Germany., Sudhop S; Center for Applied Tissue Engineering and Regenerative Medicine (CANTER), Munich University of Applied Sciences, Munich, Germany., Jurisch V; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Sini M; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Fellows MD; Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK., Cummings M; Western Michigan School of Medicine, Kalamazoo, MI, USA., Clarke J; Procella Therapeutics, Stockholm, Sweden., Baptista R; Procella Therapeutics, Stockholm, Sweden., Eroglu E; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Wolf E; Chair for Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany., Klymiuk N; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; DZHK (German Centre of Cardiovascular Research), Munich Heart Alliance, Munich, Germany., Lu K; Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, Munich, Germany., Tomasi R; Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, Munich, Germany., Dendorfer A; DZHK (German Centre of Cardiovascular Research), Munich Heart Alliance, Munich, Germany.; Walter-Brendel-Centre of Experimental Medicine, University Hospital, LMU Munich, Munich, Germany., Gaspari M; Department of Experimental and Clinical Medicine, University of Magna Grecia, Catanzaro, Italy., Parrotta E; Department of Experimental and Clinical Medicine, University of Magna Grecia, Catanzaro, Italy., Cuda G; Department of Experimental and Clinical Medicine, University of Magna Grecia, Catanzaro, Italy., Krane M; DZHK (German Centre of Cardiovascular Research), Munich Heart Alliance, Munich, Germany.; Department of Cardiovascular Surgery, INSURE, German Heart Center Munich, Technical University of Munich, Munich, Germany., Sinnecker D; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; DZHK (German Centre of Cardiovascular Research), Munich Heart Alliance, Munich, Germany., Hoppmann P; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany., Kupatt C; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. Christian.Kupatt@tum.de.; DZHK (German Centre of Cardiovascular Research), Munich Heart Alliance, Munich, Germany. Christian.Kupatt@tum.de., Fritsche-Danielson R; Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden. Regina.Fritsche-Danielson@astrazenca.com., Moretti A; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. amoretti@mytum.de.; Institute of Regenerative Medicine in Cardiology, Technical University of Munich, Munich, Germany. amoretti@mytum.de.; DZHK (German Centre of Cardiovascular Research), Munich Heart Alliance, Munich, Germany. amoretti@mytum.de., Chien KR; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden. kenneth.chien@ki.se.; Department of Medicine, Karolinska Institutet, Huddinge, Sweden. kenneth.chien@ki.se., Laugwitz KL; Medical Department I, Cardiology, Angiology, Pneumology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. KL.Laugwitz@mri.tum.de.; DZHK (German Centre of Cardiovascular Research), Munich Heart Alliance, Munich, Germany. KL.Laugwitz@mri.tum.de.
Jazyk: angličtina
Zdroj: Nature cell biology [Nat Cell Biol] 2022 May; Vol. 24 (5), pp. 659-671. Date of Electronic Publication: 2022 May 12.
DOI: 10.1038/s41556-022-00899-8
Abstrakt: Heart regeneration is an unmet clinical need, hampered by limited renewal of adult cardiomyocytes and fibrotic scarring. Pluripotent stem cell-based strategies are emerging, but unravelling cellular dynamics of host-graft crosstalk remains elusive. Here, by combining lineage tracing and single-cell transcriptomics in injured non-human primate heart biomimics, we uncover the coordinated action modes of human progenitor-mediated muscle repair. Chemoattraction via CXCL12/CXCR4 directs cellular migration to injury sites. Activated fibroblast repulsion targets fibrosis by SLIT2/ROBO1 guidance in organizing cytoskeletal dynamics. Ultimately, differentiation and electromechanical integration lead to functional restoration of damaged heart muscle. In vivo transplantation into acutely and chronically injured porcine hearts illustrated CXCR4-dependent homing, de novo formation of heart muscle, scar-volume reduction and prevention of heart failure progression. Concurrent endothelial differentiation contributed to graft neovascularization. Our study demonstrates that inherent developmental programmes within cardiac progenitors are sequentially activated in disease, enabling the cells to sense and counteract acute and chronic injury.
(© 2022. The Author(s).)
Databáze: MEDLINE
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