title: Ex vivo-expanded bone marrow CD34(+) for acute myocardial infarction treatment: in vitro and in vivo studies.
abstract: OBJECTIVE
  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.
authors.affiliation: Stem Cell Transplantation and Cellular Therapy Unit, Pediatric Onco-Hematology Division, Regina Margherita Children's Hospital, Turin, Italy. monica.gunetti@unito.it
authors.forename: Monica
authors.initials: M
authors.lastname: Gunetti
authors.forename: Alessio
authors.initials: A
authors.lastname: Noghero
authors.forename: Fabiola
authors.initials: F
authors.lastname: Molla
authors.forename: Lidia Irene
authors.initials: LI
authors.lastname: Staszewsky
authors.forename: Noeleen
authors.initials: N
authors.lastname: de Angelis
authors.forename: Annarita
authors.initials: A
authors.lastname: Soldo
authors.forename: Ilaria
authors.initials: I
authors.lastname: Russo
authors.forename: Edoardo
authors.initials: E
authors.lastname: Errichiello
authors.forename: Chiara
authors.initials: C
authors.lastname: Frasson
authors.forename: Deborah
authors.initials: D
authors.lastname: Rustichelli
authors.forename: Ivana
authors.initials: I
authors.lastname: Ferrero
authors.forename: Anna
authors.initials: A
authors.lastname: Gualandris
authors.forename: Massimo
authors.initials: M
authors.lastname: Berger
authors.forename: Massimo
authors.initials: M
authors.lastname: Geuna
authors.forename: Paolo
authors.initials: P
authors.lastname: Scacciatella
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Marra
authors.forename: Federico
authors.initials: F
authors.lastname: Bussolino
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.forename: Franca
authors.initials: F
authors.lastname: Fagioli
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000096:biosynthesis; D001853:Bone Marrow / Q000473:pathology; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D003331:Coronary Vessels / Q000601:surgery*; D004195:Disease Models, Animal; D004727:Endothelium / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D008026:Ligation; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D020127:Recovery of Function; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D015820:Cadherins; D000099152:Cadherin 5