4.7 Article

Cardiac Mesenchymal Stem Cell-like Cells Derived from a Young Patient with Bicuspid Aortic Valve Disease Have a Prematurely Aged Phenotype

Journal

BIOMEDICINES
Volume 10, Issue 12, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines10123143

Keywords

cardiac mesenchymal stem cell-like cells; bicuspid aortic valve disease; coronary artery disease; mesenchymal stem cells; ageing; senescence

Funding

  1. Wellcome Trust
  2. University of Liverpool [097826/z/11/z]

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This study compared cardiac stem cell-like cells from patients with bicuspid aortic valve disease and coronary artery disease. The results showed that stem cell-like cells from bicuspid aortic valve disease displayed a prematurely aged phenotype, with lower cell doubling rate, metabolic activity, shorter telomere lengths, and higher expression of p16.
There is significant interest in the role of stem cells in cardiac regeneration, and yet little is known about how cardiac disease progression affects native cardiac stem cells in the human heart. In this brief report, cardiac mesenchymal stem cell-like cells (CMSCLC) from the right atria of a 21-year-old female patient with a bicuspid aortic valve and aortic stenosis (referred to as biscuspid aortic valve disease BAVD-CMSCLC), were compared with those of a 78-year-old female patient undergoing coronary artery bypass surgery (referred to as coronary artery disease CAD-CMSCLC). Cells were analyzed for expression of MSC markers, ability to form CFU-Fs, metabolic activity, cell cycle kinetics, expression of NANOG and p16, and telomere length. The cardiac-derived cells expressed MSC markers and were able to form CFU-Fs, with higher rate of formation in CAD-CMSCLCs. BAVD-CMSCLCs did not display normal MSC morphology, had a much lower cell doubling rate, and were less metabolically active than CAD-CMSCLCs. Cell cycle analysis revealed a population of BAVD-CMSCLC in G2/M phase, whereas the bulk of CAD-CMSCLC were in the G0/G1 phase. BAVD-CMSCLC had lower expression of NANOG and shorter telomere lengths, but higher expression of p16 compared with the CAD-CMSCLC. In conclusion, BAVD-CMSCLC have a prematurely aged phenotype compared with CAD-CMSCLC, despite originating from a younger patient.

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