Platelet-Derived Growth Factor Receptor-Alpha Expressing Cardiac Progenitor Cells Can Be Derived from Previously

Thi Y L Le1,2, Hilda A Pickett3, Cristobal G Dos Remedios4

  • 11 Center for Heart Research, Westmead Institute for Medical Research, The University of Sydney , Westmead, Australia .

Insights

Previously cryopreserved human heart tissue can yield cardiac progenitor cells (CPCs) for heart failure therapies. This study successfully isolated multipotent CPCs from banked heart samples, supporting tissue banking for future treatments.

Area of Science:

  • Regenerative Medicine
  • Cardiovascular Biology
  • Cell Biology

Background:

  • Cardiac progenitor cells (CPCs) are crucial for heart repair and are typically derived from donor biopsies.
  • Access to CPCs for clinical trials is often limited by sample availability and timely procurement.
  • Utilizing previously cryopreserved human heart tissue offers a potential solution for consistent CPC sourcing.

Purpose of the Study:

  • To investigate the feasibility of isolating and expanding cardiac progenitor cells (CPCs) from cryopreserved human heart tissue.
  • To characterize the phenotype, pluripotency, and multipotent differentiation capacity of CPCs derived from banked samples.
  • To assess the impact of donor age on CPC characteristics, including proliferative and self-renewing potential.

Main Methods:

  • Isolation of CPCs from cryopreserved human heart samples.
  • Flow cytometry and immunofluorescence for cell surface marker analysis (PDGFRα, CD90, CD31, DDR2, Vimentin, CD45).
  • Quantitative PCR for pluripotency gene expression (SOX2, NANOG, MYC, KLF4).
  • Colony-forming assays, in vitro differentiation assays (smooth muscle, endothelial, cardiomyocyte-like cells), and single-cell assays.
  • Telomere length and telomerase activity assessment.

Main Results:

  • CPCs were successfully isolated from cryopreserved human heart samples, expressing key fibroblast, mesenchymal, and pluripotency markers while lacking hematopoietic markers.
  • Cells derived from younger hearts exhibited superior proliferative and self-renewing capacity compared to those from aged hearts, correlating with telomere length.
  • Enriched PDGFRα+/CD90+/CD31- CPCs demonstrated clonogenicity and multipotent differentiation potential into smooth muscle, endothelial, and cardiomyocyte-like lineages.
  • Prolonged self-renewing capacity (>2 months) and sustained pluripotency gene expression were observed in single-cell assays.

Conclusions:

  • Multipotent cardiac progenitor cells (CPCs) can be effectively isolated and expanded from previously cryopreserved human heart tissue.
  • Cardiac tissue banking provides a viable strategy for ensuring accessible, high-quality CPCs for future cell-based regenerative therapies for heart failure.
  • Donor age influences CPC function, highlighting the importance of sample selection for optimal therapeutic outcomes.

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