title: Intracoronary Delivery of Human Mesenchymal/Stromal Stem Cells: Insights from Coronary Microcirculation Invasive Assessment in a Swine Model.
abstract: BACKGROUND
  Mesenchymal stem/stromal cells have unique properties favorable to their use in clinical practice and have been studied for cardiac repair. However, these cells are larger than coronary microvessels and there is controversy about the risk of embolization and microinfarctions, which could jeopardize the safety and efficacy of intracoronary route for their delivery. The index of microcirculatory resistance (IMR) is an invasive method for quantitatively assessing the coronary microcirculation status.
  
  
  OBJECTIVE
  To examine heart microcirculation after intracoronary injection of mesenchymal stem/stromal cells with the index of microcirculatory resistance.
  
  
  METHODS
  Healthy swine were randomized to receive by intracoronary route either 30x106 MSC or the same solution with no cells (1% human albumin/PBS) (placebo). Blinded operators took coronary pressure and flow measurements, prior to intracoronary infusion and at 5 and 30 minutes post-delivery. Coronary flow reserve (CFR) and the IMR were compared between groups.
  
  
  RESULTS
  CFR and IMR were done with a variance within the 3 transit time measurements of 6% at rest and 11% at maximal hyperemia. After intracoronary infusion there were no significant differences in CFR. The IMR was significantly higher in MSC-injected animals (at 30 minutes, 14.2U vs. 8.8U, p = 0.02) and intragroup analysis showed a significant increase of 112% from baseline to 30 minutes after cell infusion, although no electrocardiographic changes or clinical deterioration were noted.
  
  
  CONCLUSIONS
  Overall, this study provides definitive evidence of microcirculatory disruption upon intracoronary administration of mesenchymal stem/stromal cells, in a large animal model closely resembling human cardiac physiology, function and anatomy.
authors.affiliation: Cardiology Department, Hospital de Santa Marta, Lisboa, Portugal; Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: António
authors.initials: A
authors.lastname: Fiarresga
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Márcia F
authors.initials: MF
authors.lastname: Mata
authors.affiliation: National Institute for Agrarian and Veterinary Research, Oeiras, Portugal.
authors.forename: Sandra
authors.initials: S
authors.lastname: Cavaco-Gonçalves
authors.affiliation: Cardiology Department, Hospital de Santa Marta, Lisboa, Portugal.
authors.forename: Mafalda
authors.initials: M
authors.lastname: Selas
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Irina N
authors.initials: IN
authors.lastname: Simões
authors.affiliation: Cardiology Department, Hospital de Santa Marta, Lisboa, Portugal.
authors.forename: Eunice
authors.initials: E
authors.lastname: Oliveira
authors.affiliation: Faculty of Veterinary Medicine, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Belmira
authors.initials: B
authors.lastname: Carrapiço
authors.affiliation: Nova Medical School, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Cardim
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Joaquim M S
authors.initials: JM
authors.lastname: Cabral
authors.affiliation: Cardiology Department, Hospital de Santa Marta, Lisboa, Portugal.
authors.forename: Rui Cruz
authors.initials: RC
authors.lastname: Ferreira
authors.affiliation: Department of Bioengineering and iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Cláudia L
authors.initials: CL
authors.lastname: da Silva
mesh_terms: D000818:Animals; D003326:Coronary Circulation; D003331:Coronary Vessels / Q000166:cytology* / Q000502:physiology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008833:Microcirculation; D013552:Swine