In vitro expansion of human cardiac progenitor cells: Exploring 'omics tools for characterization of cell-based allogeneic products

Patrícia Gomes-Alves, Margarida Serra, C. Brito, C. P. Ricardo, Jorge R. Cunha, M. F. Sousa, M. Teresa Blazquez-Sanchez, António Bernad, M. J T Carrondo, L. Rodriguez-Borlado, P. M. Alves

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Human cardiac stem/progenitor cells (hCPCs) have been shown to be capable to regenerate contractile myocardium. However, because of their relative low abundance in the heart, in vitro expansion of hCPC is mandatory to achieve necessary quantities for allogeneic or autologous cardiac regeneration therapy applications (106-109 cells/patient). Up to now, cell number requirements of ongoing phase I/IIa trials have been fulfilled with production in static monolayer cultures. However, this manufacturing process poses critical limitations when moving to the following clinical phases where hundreds of patients will be enrolled. For this, increased process yield is required, while guaranteeing the quality of the cell-based products. In this work, we developed and validated a robust, scalable, and good manufacturing practice (GMP)-compatible bioprocess for the expansion of high-quality hCPC. We applied platforms extensively used by the biopharmaceutical industry, such as microcarrier technology and stirred systems, and assessed culture conditions' impact on hCPC's quality and potency, as required by regulatory agencies. Complementary analytical assays including gene expression microarrays and mass spectrometry-based approaches were explored to compare transcriptome, proteome, surface markers, and secretion profiles of hCPC cultured in static monolayers and in stirred microcarrier-based systems. Our results show that stirred microcarrier-based culture systems enabled achieving more than 3-fold increase in hCPC expansion, when compared with traditional static monolayers, while retaining cell's phenotype and similar "omics" profiles. These findings demonstrate that this change in the production process does not affect cell's identity and quality, with potential to be translated into a transversal production platform for clinical development of stem-cell therapies.

Original languageEnglish
Pages (from-to)96-110
Number of pages15
JournalTranslational Research
Publication statusPublished - 1 May 2016


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