Maass, Martina, Krausgrill, Benjamin, Eschrig, Simon, Kaluschke, Tobias, Urban, Katja, Peinkofer, Gabriel, Plenge, Tobias G., Oeckenpoehler, Simon, Raths, Martin, Ladage, Dennis ORCID: 0000-0002-4512-0917, Halbach, Marcel, Hescheler, Juergen and Mueller-Ehmsen, Jochen (2017). Intramyocardially Transplanted Neonatal Cardiomyocytes (NCMs) Show Structural and Electrophysiological Maturation and Integration and Dose-Dependently Stabilize Function of Infarcted Rat Hearts. Cell Transplant., 26 (1). S. 157 - 171. PUTNAM VALLEY: COGNIZANT COMMUNICATION CORP. ISSN 1555-3892

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Abstract

Cardiac cell replacement therapy is a promising therapy to improve cardiac function in heart failure. Persistence, structural and functional maturation, and integration of transplanted cardiomyocytes into recipients' hearts are crucial for a safe and efficient replacement of lost cells. We studied histology, electrophysiology, and quantity of intramyocardially transplanted rat neonatal cardiomyocytes (NCMs) and performed a detailed functional study with repeated invasive (pressure volume catheter) and noninvasive (echocardiography) analyses of infarcted female rat hearts including pharmacological stress before and 3 weeks after intramyocardial injection of 5 x 10(6) (low NCM) or 25 x 10(6) (high NCM) syngeneic male NCMs or medium as placebo (Ctrl). Quantitative real-time polymerase chain reaction (PCR) for Y-chromosome confirmed a fivefold higher persisting male cell number in high NCM versus low NCM after 3 weeks. Sharp electrode measurements within viable slices of recipient hearts demonstrated that transplanted NCMs integrate into host myocardium and mature to an almost adult phenotype, which might be facilitated through gap junctions between host myocardium and transplanted NCMs as indicated by connexin43 in histology. Ejection fraction of recipient hearts was severely impaired after ligation of left anterior descending (LAD; pressure volume catheter: 39.2 +/- 3.6%, echocardiography: 39.9 +/- 1.4%). Repeated analyses revealed a significant further decline within 3 weeks in Ctrl and a dose-dependent stabilization in cell-treated groups. Consistently, stabilized cardiac function/morphology in cell-treated groups was seen in stroke volume, cardiac output, ventricle length, and wall thickness. Our findings confirm that cardiac cell replacement is a promising therapy for ischemic heart disease since immature cardiomyocytes persist, integrate, and mature after intramyocardial transplantation, and they dose-dependently stabilize cardiac function after myocardial infarction.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Maass, MartinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Krausgrill, BenjaminUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eschrig, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaluschke, TobiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Urban, KatjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peinkofer, GabrielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Plenge, Tobias G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oeckenpoehler, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Raths, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ladage, DennisUNSPECIFIEDorcid.org/0000-0002-4512-0917UNSPECIFIED
Halbach, MarcelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hescheler, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller-Ehmsen, JochenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-247617
DOI: 10.3727/096368916X692870
Journal or Publication Title: Cell Transplant.
Volume: 26
Number: 1
Page Range: S. 157 - 171
Date: 2017
Publisher: COGNIZANT COMMUNICATION CORP
Place of Publication: PUTNAM VALLEY
ISSN: 1555-3892
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CELL-DERIVED CARDIOMYOCYTES; MURINE FETAL CARDIOMYOCYTES; EMBRYONIC STEM-CELLS; BONE-MARROW-CELLS; MYOCARDIAL-INFARCTION; MORPHOLOGICAL MATURATION; CARDIAC REPAIR; ISCHEMIC-HEART; MOUSE HEARTS; IN-VITROMultiple languages
Cell & Tissue Engineering; Medicine, Research & Experimental; TransplantationMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24761

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