title: Human umbilical cord tissue-derived mesenchymal stromal cells attenuate remodeling after myocardial infarction by proangiogenic, antiapoptotic, and endogenous cell-activation mechanisms.
abstract: BACKGROUND
  Among the plethora of cells under investigation to restore a functional myocardium, mesenchymal stromal cells (MSCs) have been granted considerable interest. However, whereas the beneficial effects of bone marrow MSCs (BM-MSCs) in the context of the diseased heart are widely reported, data are still scarce on MSCs from the umbilical cord matrix (UCM-MSCs). Herein we report on the effect of UCM-MSC transplantation to the infarcted murine heart, seconded by the dissection of the molecular mechanisms at play.
  
  
  METHODS
  Human umbilical cord tissue-derived MSCs (UCX®), obtained by using a proprietary technology developed by ECBio, were delivered via intramyocardial injection to C57BL/6 females subjected to permanent ligation of the left descending coronary artery. Moreover, medium produced by cultured UCX® preconditioned under normoxia (CM) or hypoxia (CMH) was collected for subsequent in vitro assays.
  
  
  RESULTS
  Evaluation of the effects upon intramyocardial transplantation shows that UCX® preserved cardiac function and attenuated cardiac remodeling subsequent to myocardial infarction (MI). UCX® further led to increased capillary density and decreased apoptosis in the injured tissue. In vitro, UCX®-conditioned medium displayed (a) proangiogenic activity by promoting the formation of capillary-like structures by human umbilical vein endothelial cells (HUVECs), and (b) antiapoptotic activity in HL-1 cardiomyocytes subjected to hypoxia. Moreover, in adult murine cardiac Sca-1+ progenitor cells (CPCs), conditioned medium enhanced mitogenic activity while activating a gene program characteristic of cardiomyogenic differentiation.
  
  
  CONCLUSIONS
  UCX® preserve cardiac function after intramyocardial transplantation in a MI murine model. The cardioprotective effects of UCX® were attributed to paracrine mechanisms that appear to enhance angiogenesis, limit the extent of the apoptosis, augment proliferation, and activate a pool of resident CPCs. Overall, these results suggest that UCX® should be considered an alternative cell source when designing new therapeutic approaches to treat MI.
authors.forename: Diana
authors.initials: D
authors.lastname: Santos Nascimento
authors.forename: Diogo
authors.initials: D
authors.lastname: Mosqueira
authors.forename: Luís Moura
authors.initials: LM
authors.lastname: Sousa
authors.forename: Mariana
authors.initials: M
authors.lastname: Teixeira
authors.forename: Mariana
authors.initials: M
authors.lastname: Filipe
authors.forename: Tatiana Pinho
authors.initials: TP
authors.lastname: Resende
authors.forename: Ana Francisca
authors.initials: AF
authors.lastname: Araújo
authors.forename: Mariana
authors.initials: M
authors.lastname: Valente
authors.forename: Joana
authors.initials: J
authors.lastname: Almeida
authors.forename: José Paulo
authors.initials: JP
authors.lastname: Martins
authors.forename: Jorge Miguel
authors.initials: JM
authors.lastname: Santos
authors.forename: Rita Nogueira
authors.initials: RN
authors.lastname: Bárcia
authors.forename: Pedro
authors.initials: P
authors.lastname: Cruz
authors.forename: Helder
authors.initials: H
authors.lastname: Cruz
authors.forename: Perpétua
authors.initials: P
authors.lastname: Pinto-do-Ó
mesh_terms: D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication; D020257:Ventricular Remodeling