title: Increasing short-term cardiomyocyte progenitor cell (CMPC) survival by necrostatin-1 did not further preserve cardiac function.
abstract: OBJECTIVE
  One of the main limitations for an effective cell therapy for the heart is the poor cell engraftment after implantation, which is partly due to a large percentage of cell death in the hostile myocardium. In the present study, we investigated the utilization of necrostatin-1 (Nec-1) as a possible attenuator of cell death in cardiomyocyte progenitor cells (CMPCs).
  
  
  RESULTS
  In a mouse model of myocardial infarction, survival of CMPCs 3 days after intra-myocardial injection was 39 ± 9% higher in cells pretreated with the Nec-1 compound. However, the increase in cell number was not sustained over 28 days, and did not translate into improved cardiac function (ejection fraction %, 20.6 ± 2.1 vs. 21.4 ± 2.5 for vehicle and Nec-1-treated CMPC, respectively). Nonetheless, Nec-1 rescued CMPCs remained functionally competent.
  
  
  CONCLUSIONS
  A pharmacological pretreatment approach to solely enhance cell survival on the short term does not seem to be effective strategy to improve cardiac cell therapy with CMPCs.
authors.affiliation: Division Heart and Lungs, Department of Cardiology, Experimental Cardiology Laboratory, University Medical Center Utrecht, Heidelberglaan 100, room G02.523, Utrecht 3584 CX, The Netherlands.
authors.forename: Dries
authors.initials: D
authors.lastname: Feyen
authors.forename: Roberto
authors.initials: R
authors.lastname: Gaetani
authors.forename: Jia
authors.initials: J
authors.lastname: Liu
authors.forename: Willy
authors.initials: W
authors.lastname: Noort
authors.forename: Anton
authors.initials: A
authors.lastname: Martens
authors.forename: Krista
authors.initials: K
authors.lastname: den Ouden
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013318:Stroke Volume; D013997:Time Factors; D014161:Transduction, Genetic; D014162:Transfection; D016277:Ventricular Function, Left
chemical_list: D007093:Imidazoles; D007211:Indoles; C507699:necrostatin-1; D049452:Green Fluorescent Proteins
keywords: BLI; Cardiac cell therapy; Cardiac progenitor cells; Cell survival; Necrostatin