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

Lookup NU author(s): Rachel Oldershaw, Professor Gavin RichardsonORCiD, Pip Carling, Dr Andrew OwensORCiD, Dr Annette Meeson

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

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 CADCMSCLCs. 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.


Publication metadata

Author(s): Oldershaw RA, Richardson GD, Carling P, Owens WA, Lundy DJ, Meeson A

Publication type: Article

Publication status: Published

Journal: Biomedicines

Year: 2022

Volume: 10

Issue: 12

Online publication date: 06/12/2022

Acceptance date: 28/11/2022

Date deposited: 06/12/2022

ISSN (electronic): 2227-9059

Publisher: MDPI

URL: https://doi.org/10.3390/biomedicines10123143

DOI: 10.3390/biomedicines10123143

Data Access Statement: Not applicable.


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Funding

Funder referenceFunder name
097826/z/11/z
Wellcome

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