Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies |
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Authors: | Gunetti Monica Noghero Alessio Molla Fabiola Staszewsky Lidia Irene de Angelis Noeleen Soldo Annarita Russo Ilaria Errichiello Edoardo Frasson Chiara Rustichelli Deborah Ferrero Ivana Gualandris Anna Berger Massimo Geuna Massimo Scacciatella Paolo Basso Giuseppe Marra Sebastiano Bussolino Federico Latini Roberto Fagioli Franca |
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Institution: | Stem Cell Transplantation and Cellular Therapy Unit, Pediatric Onco-Hematology Division, Regina Margherita Children's Hospital, Turin, Italy. monica.gunetti@unito.it |
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Abstract: | Background aimsBone 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.MethodsThe 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.ResultsGene 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.ConclusionsOur 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. |
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