Antigenic, functional and molecular characterization of human cardiac pericytes from newborn and grown-up congenital heart disease patients

  • Aleksandra Judina

Student thesis: Master's ThesisMaster of Science by Research (MScR)

Abstract

Background: Pericytes represent a heterogeneous and abundant population of cells that can contribute to tissue regeneration in vivo and can be expanded in vitro to be used for regenerative medicine applications. However, ageing can blunt the regenerative potential of cells. We have previously derived cardiac pericytes (CPs) from myocardial leftovers of new-born patients operated for correction of congenital heart disease (CHD). A high number of patients reach the adult life and still needs therapeutic intervention.Aims: To investigate if adult heart contains a population of CPs and if so, whether ageing affects CPs phenotype and functional properties in vitro.Methods: We isolated and expanded to passage 5 cells from newborn (nCPs, N=3, age<30 days) and adult (aCPs, N=3, age 14 to 54 years) patients. Antigenic profile, growth rate, secretome, angiogenic activity and vascular plasticity were investigated and compared.Results: After in vitro expansion, both aCPs and nCPs were positive for CD34, NG2, PDGFRβ but negative for CD146 and endothelial and vascular smooth muscle cell (VSMC) markers. Cells also express similar levels of stemness markers, were endowed with the same average growth rate and secreted similar amounts of pro-angiogenic factors: VEGF, Ang-1, and Ang-2. Only aCPs cells significantly increased the formation of tubular networks by cardiac endothelial cells (ECs), while for nCPs neither secretome nor cells showed this capacity when co-cultured with the ECs. Hence further investigation with increased sample number is required for angiogenic capacity assessment. Finally, all CPs were able to express VSMC markers upon exposure to differentiation media.Conclusion: Our results show for the first time that within adult human heart there is a population of CPs previously only reported for newborn hearts. These aCPs present similar phenotypic and functional properties to nCPs.
Date of Award25 Sept 2018
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorMassimo Caputo (Supervisor) & Paolo R Madeddu (Supervisor)

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