Hematopoietic stem-cell senescence and myocardial repair - Coronary artery disease genotype/phenotype analysis of post-MI myocardial regeneration response induced by CABG/CD133+ bone marrow hematopoietic stem cell treatment in RCT PERFECT Phase 3

Autor: Markus Wolfien, Denise Klatt, Amankeldi A. Salybekov, Masaaki Ii, Miki Komatsu-Horii, Ralf Gaebel, Julia Philippou-Massier, Eric Schrinner, Hiroshi Akimaru, Erika Akimaru, Robert David, Jens Garbade, Jan Gummert, Axel Haverich, Holger Hennig, Hiroto Iwasaki, Alexander Kaminski, Atsuhiko Kawamoto, Christian Klopsch, Johannes T. Kowallick, Stefan Krebs, Julia Nesteruk, Hermann Reichenspurner, Christian Ritter, Christof Stamm, Ayumi Tani-Yokoyama, Helmut Blum, Olaf Wolkenhauer, Axel Schambach, Takayuki Asahara, Gustav Steinhoff
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: EBioMedicine, Vol 57, Iss , Pp 102862- (2020)
Druh dokumentu: article
ISSN: 2352-3964
58128840
DOI: 10.1016/j.ebiom.2020.102862
Popis: Background: Bone marrow stem cell clonal dysfunction by somatic mutation is suspected to affect post-infarction myocardial regeneration after coronary bypass surgery (CABG). Methods: Transcriptome and variant expression analysis was studied in the phase 3 PERFECT trial post myocardial infarction CABG and CD133+ bone marrow derived hematopoetic stem cells showing difference in left ventricular ejection fraction (∆LVEF) myocardial regeneration Responders (n=14; ∆LVEF +16% day 180/0) and Non-responders (n=9; ∆LVEF -1.1% day 180/0). Subsequently, the findings have been validated in an independent patient cohort (n=14) as well as in two preclinical mouse models investigating SH2B3/LNK antisense or knockout deficient conditions. Findings: 1. Clinical: R differed from NR in a total of 161 genes in differential expression (n=23, q
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