Ex vivo-expanded bone marrow CD34+ for acute myocardial infarction treatment: In vitro and in vivo studies

Monica Gunetti, Alessio Noghero, Fabiola Molla, Lidia Irene Staszewsky, Noeleen De Angelis, Annarita Soldo, Ilaria Russo, Edoardo Errichiello, Chiara Frasson, Deborah Rustichelli, Ivana Ferrero, Anna Gualandris, Massimo Berger, Massimo Geuna, Paolo Scacciatella, Giuseppe Basso, Sebastiano Marra, Federico Bussolino, Roberto Latini, Franca Fagioli

Research output: Contribution to journalArticlepeer-review

Abstract

Background aims. Bone marrow (BM)-derived cells appear to be a promising therapeutic source for the treatment of acute myocardial infarction (AMI). However, the quantity and quality of the cells to be used, along with the appropriate time of administration, still need to be defined. We thus investigated the use of BM CD34+-derived cells as cells suitable for a cell therapy protocol (CTP) in the treatment of experimental AMI. Methods. The need for a large number of cells was satisfied by the use of a previously established protocol allowing the expansion of human CD34+ cells isolated from neonatal and adult hematopoietic tissues. We evaluated gene expression, endothelial differentiation potential and cytokine release by BM-derived cells during in vitro culture. Basal and expanded CD34+ cells were used as a delivery product in a murine AMI model consisting of a coronary artery ligation (CAL). Cardiac function recovery was evaluated after injecting basal or expanded cells. Results. Gene expression analysis of in vitro-expanded cells revealed that endothelial markers were up-regulated during culture. Moreover, expanded cells generated a CD14+ subpopulation able to differentiate efficiently into VE-cadherin-expressing cells. In vivo, we observed a cardiac function recovery in mice sequentially treated with basal and expanded cells injected 4 h and 7 days after CAL, respectively. Conclusions. Our data suggest that combining basal and expanded BM-derived CD34+ cells in a specific temporal pattern of administration might represent a promising strategy for a successful cell-based therapy.

Original languageEnglish
Pages (from-to)1140-1152
Number of pages13
JournalCytotherapy
Volume13
Issue number9
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Cellular therapy
  • cytotherapy
  • stem cells
  • translational research

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Molecular Medicine

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