title: Human cardiac progenitor cells engineered with Pim-I kinase enhance myocardial repair.
abstract: OBJECTIVE
  The goal of this study was to demonstrate the enhancement of human cardiac progenitor cell (hCPC) reparative and regenerative potential by genetic modification for the treatment of myocardial infarction.
  
  
  BACKGROUND
  Regenerative potential of stem cells to repair acute infarction is limited. Improved hCPC survival, proliferation, and differentiation into functional myocardium will increase efficacy and advance translational implementation of cardiac regeneration.
  
  
  METHODS
  hCPCs isolated from the myocardium of heart failure patients undergoing left ventricular assist device implantation were engineered to express green fluorescent protein (hCPCe) or Pim-1-GFP (hCPCeP). Functional tests of hCPC regenerative potential were performed with immunocompromised mice by using intramyocardial adoptive transfer injection after infarction. Myocardial structure and function were monitored by echocardiographic and hemodynamic assessment for 20 weeks after delivery. hCPCe and hCPCeP expressing luciferase were observed by using bioluminescence imaging to noninvasively track persistence.
  
  
  RESULTS
  hCPCeP exhibited augmentation of reparative potential relative to hCPCe control cells, as shown by significantly increased proliferation coupled with amelioration of infarction injury and increased hemodynamic performance at 20 weeks post-transplantation. Concurrent with enhanced cardiac structure and function, hCPCeP demonstrated increased cellular engraftment and differentiation with improved vasculature and reduced infarct size. Enhanced persistence of hCPCeP versus hCPCe was revealed by bioluminescence imaging at up to 8 weeks post-delivery.
  
  
  CONCLUSIONS
  Genetic engineering of hCPCs with Pim-1 enhanced repair of damaged myocardium. Ex vivo gene delivery to modify stem cells has emerged as a viable option addressing current limitations in the field. This study demonstrates that efficacy of hCPCs from the failing myocardium can be safely and significantly enhanced through expression of Pim-1 kinase, setting the stage for use of engineered cells in pre-clinical settings.
authors: SDSU Heart Research Institute, San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, USA.
authors: Sadia
authors: S
authors: Mohsin
authors: Mohsin
authors: M
authors: Khan
authors: Haruhiro
authors: H
authors: Toko
authors: Brandi
authors: B
authors: Bailey
authors: Christopher T
authors: CT
authors: Cottage
authors: Kathleen
authors: K
authors: Wallach
authors: Divya
authors: D
authors: Nag
authors: Andrew
authors: A
authors: Lee
authors: Sailay
authors: S
authors: Siddiqi
authors: Feng
authors: F
authors: Lan
authors: Kimberlee M
authors: KM
authors: Fischer
authors: Natalie
authors: N
authors: Gude
authors: Pearl
authors: P
authors: Quijada
authors: Daniele
authors: D
authors: Avitabile
authors: Silvia
authors: S
authors: Truffa
authors: Brett
authors: B
authors: Collins
authors: Walter
authors: W
authors: Dembitsky
authors: Joseph C
authors: JC
authors: Wu
authors: Mark A
authors: MA
authors: Sussman
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004452:Echocardiography; D015870:Gene Expression; D005818:Genetic Engineering; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006439:Hemodynamics; D006801:Humans; D008163:Luminescent Measurements; D051379:Mice; D009203:Myocardial Infarction / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000201:enzymology / Q000637:transplantation*; D009389:Neovascularization, Pathologic; D051573:Proto-Oncogene Proteins c-pim-1 / Q000235:genetics / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000201:enzymology
chemical_list: D049452:Green Fluorescent Proteins; D051573:Proto-Oncogene Proteins c-pim-1