PMID- 22619278
OWN - NLM
STAT- MEDLINE
DCOM- 20120828
LR  - 20220309
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 111
IP  - 1
DP  - 2012 Jun 22
TI  - Preservation of myocardial structure is enhanced by pim-1 engineering of bone 
      marrow cells.
PG  - 77-86
LID - 10.1161/CIRCRESAHA.112.265207 [doi]
AB  - RATIONALE: Bone marrow-derived cells to treat myocardial injury improve cardiac 
      function and support beneficial cardiac remodeling. However, survival of stem 
      cells is limited due to low proliferation of transferred cells. OBJECTIVE: To 
      demonstrate long-term potential of c-kit(+) bone marrow stem cells (BMCs) 
      enhanced with Pim-1 kinase to promote positive cardiac remodeling. METHODS AND 
      RESULTS: Lentiviral modification of c-kit(+) BMCs to express Pim-1 (BMCeP) 
      increases proliferation and expression of prosurvival proteins relative to BMCs 
      expressing green fluorescent protein (BMCe). Intramyocardial delivery of BMCeP at 
      time of infarction supports improvements in anterior wall dimensions and prevents 
      left ventricle dilation compared with hearts treated with vehicle alone. 
      Reduction of the akinetic left ventricular wall was observed in BMCeP-treated 
      hearts at 4 and 12 weeks after infarction. Early recovery of cardiac function in 
      BMCeP-injected hearts facilitated modest improvements in hemodynamic function up 
      to 12 weeks after infarction between cell-treated groups. Persistence of BMCeP is 
      improved relative to BMCe within the infarct together with increased recruitment 
      of endogenous c-kit(+) cells. Delivery of BMC populations promotes cellular 
      hypertrophy in the border and infarcted regions coupled with an upregulation of 
      hypertrophic genes. Thus, BMCeP treatment yields improved structural remodeling 
      of infarcted myocardium compared with control BMCs. CONCLUSIONS: Genetic 
      modification of BMCs with Pim-1 may serve as a therapeutic approach to promote 
      recovery of myocardial structure. Future approaches may take advantage of 
      salutary BMC actions in conjunction with other stem cell types to increase 
      efficacy of cellular therapy and improve myocardial performance in the injured 
      myocardium.
FAU - Quijada, Pearl
AU  - Quijada P
AD  - San Diego State University Heart Institute, CA, USA.
FAU - Toko, Haruhiro
AU  - Toko H
FAU - Fischer, Kimberlee M
AU  - Fischer KM
FAU - Bailey, Brandi
AU  - Bailey B
FAU - Reilly, Patrick
AU  - Reilly P
FAU - Hunt, Kristin D
AU  - Hunt KD
FAU - Gude, Natalie A
AU  - Gude NA
FAU - Avitabile, Daniele
AU  - Avitabile D
FAU - Sussman, Mark A
AU  - Sussman MA
LA  - eng
GR  - RC1 HL100891/HL/NHLBI NIH HHS/United States
GR  - R01 HL105759/HL/NHLBI NIH HHS/United States
GR  - R21HL102613/HL/NHLBI NIH HHS/United States
GR  - R01HL105759/HL/NHLBI NIH HHS/United States
GR  - R21 HL102714/HL/NHLBI NIH HHS/United States
GR  - R21HL102714/HL/NHLBI NIH HHS/United States
GR  - P01HL085577/HL/NHLBI NIH HHS/United States
GR  - R01HL067245/HL/NHLBI NIH HHS/United States
GR  - R37 HL091102/HL/NHLBI NIH HHS/United States
GR  - R37HL091102/HL/NHLBI NIH HHS/United States
GR  - RC1HL100891/HL/NHLBI NIH HHS/United States
GR  - R01 HL067245/HL/NHLBI NIH HHS/United States
GR  - P01 HL085577/HL/NHLBI NIH HHS/United States
GR  - R21 HL104544/HL/NHLBI NIH HHS/United States
GR  - R01 HL113656/HL/NHLBI NIH HHS/United States
GR  - R21 HL102613/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120522
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Cytokines)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.11.1 (PIM1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-pim-1)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Bone Marrow Cells/*metabolism/pathology
MH  - *Bone Marrow Transplantation
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Female
MH  - Green Fluorescent Proteins/genetics/metabolism
MH  - Heart Failure/metabolism/physiopathology/prevention & control
MH  - Humans
MH  - Hypertrophy, Left Ventricular/metabolism/physiopathology/prevention & control
MH  - Lentivirus/genetics
MH  - Male
MH  - Mice
MH  - Myocardial Contraction
MH  - Myocardial Infarction/diagnostic imaging/metabolism/physiopathology/*surgery
MH  - Myocardium/*metabolism/pathology
MH  - Phenotype
MH  - Proto-Oncogene Proteins c-kit/metabolism
MH  - Proto-Oncogene Proteins c-pim-1/genetics/*metabolism
MH  - Recovery of Function
MH  - *Regeneration
MH  - Signal Transduction
MH  - Time Factors
MH  - *Tissue Engineering/methods
MH  - Transduction, Genetic
MH  - Ultrasonography
MH  - Ventricular Function, Left
MH  - Ventricular Remodeling
PMC - PMC3398618
MID - NIHMS386351
EDAT- 2012/05/24 06:00
MHDA- 2012/08/29 06:00
PMCR- 2013/06/22
CRDT- 2012/05/24 06:00
PHST- 2012/05/24 06:00 [entrez]
PHST- 2012/05/24 06:00 [pubmed]
PHST- 2012/08/29 06:00 [medline]
PHST- 2013/06/22 00:00 [pmc-release]
AID - CIRCRESAHA.112.265207 [pii]
AID - 10.1161/CIRCRESAHA.112.265207 [doi]
PST - ppublish
SO  - Circ Res. 2012 Jun 22;111(1):77-86. doi: 10.1161/CIRCRESAHA.112.265207. Epub 2012 
      May 22.