Clinical scale ex vivo expansion of cord blood-derived outgrowth endothelial progenitor cells is associated with high incidence of karyotype aberrations

Mirko Corselli, Alessia Parodi, Massimo Mogni, Nadia Sessarego, Annalisa Kunkl, Franca Dagna-Bricarelli, Adalberto Ibatici, Sarah Pozzi, Andrea Bacigalupo, Francesco Frassoni, Giovanna Piaggio

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: Endothelial progenitor cells (EPCs) are involved in neovessel formation. So far, therapeutic angiogenesis is hampered by the low frequency and limited proliferative potential of these cells isolated from peripheral blood. Recently, it has been shown that cord blood-derived EPCs (CB EPCs) can be ex vivo expanded on a clinical scale. In this study, we evaluated the expansion potential of CB EPCs together with their phenotypic, functional, and chromosomal stability over time. Materials and Methods: Flow cytometry, in vitro tube formation, and proliferation assays were performed to characterize CB EPC-derived cells. Chromosomal stability was evaluated by karyotype analysis. In vitro and in vivo tumorigenicity was evaluated by soft agar assay and injection into nonobese diabetic/severe combined immunodeficient mice, respectively. Results: We showed that CB EPC-derived cells displayed phenotypic and functional features of EPCs, although a process of maturation was observed over time. Although we confirmed that CB EPCs have a greater expansion potential compared to peripheral blood EPCS, we observed a high incidence of cytogenetic alterations (71%) in the expanded endothelial cell population, even at early times of culture. In two cases, spontaneous transformation in vitro was documented, but none of the samples tested showed tumorigenic potential in vivo. Conversely, no karyotype alterations have been observed on peripheral blood EPCs-derived cells. Conclusions: We confirm that CB represents a good source for clinical ex vivo expansion of EPCs. However, because of high frequency of karyotype alterations, these cells cannot be considered free of risk in clinical application.

Original languageEnglish
Pages (from-to)340-349
Number of pages10
JournalExperimental Hematology
Volume36
Issue number3
DOIs
Publication statusPublished - Mar 2008

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Genetics
  • Hematology
  • Oncology
  • Transplantation

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