Document Detail


Preservation of myocardial structure is enhanced by pim-1 engineering of bone marrow cells.
MedLine Citation:
PMID:  22619278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Pearl Quijada; Haruhiro Toko; Kimberlee M Fischer; Brandi Bailey; Patrick Reilly; Kristin D Hunt; Natalie A Gude; Daniele Avitabile; Mark A Sussman
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-22
Journal Detail:
Title:  Circulation research     Volume:  111     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-22     Completed Date:  2012-08-28     Revised Date:  2013-06-25    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  77-86     Citation Subset:  IM    
Affiliation:
San Diego State University Heart Institute, CA, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis
Bone Marrow Cells / metabolism*,  pathology
Bone Marrow Transplantation*
Cell Proliferation
Cell Survival
Cells, Cultured
Cytokines / metabolism
Disease Models, Animal
Female
Green Fluorescent Proteins / genetics,  metabolism
Heart Failure / metabolism,  physiopathology,  prevention & control
Humans
Hypertrophy, Left Ventricular / metabolism,  physiopathology,  prevention & control
Lentivirus / genetics
Male
Mice
Myocardial Contraction
Myocardial Infarction / metabolism,  physiopathology,  surgery*,  ultrasonography
Myocardium / metabolism*,  pathology
Phenotype
Proto-Oncogene Proteins c-kit / metabolism
Proto-Oncogene Proteins c-pim-1 / genetics,  metabolism*
Recovery of Function
Regeneration*
Signal Transduction
Time Factors
Tissue Engineering* / methods
Transduction, Genetic
Ventricular Function, Left
Ventricular Remodeling
Grant Support
ID/Acronym/Agency:
P01 HL085577/HL/NHLBI NIH HHS; P01HL085577/HL/NHLBI NIH HHS; R01 HL067245/HL/NHLBI NIH HHS; R01 HL105759/HL/NHLBI NIH HHS; R01 HL113656/HL/NHLBI NIH HHS; R01HL067245/HL/NHLBI NIH HHS; R01HL105759/HL/NHLBI NIH HHS; R21 HL102613/HL/NHLBI NIH HHS; R21 HL102714/HL/NHLBI NIH HHS; R21 HL104544/HL/NHLBI NIH HHS; R21 HL104544/HL/NHLBI NIH HHS; R21HL102613/HL/NHLBI NIH HHS; R21HL102714/HL/NHLBI NIH HHS; R37 HL091102/HL/NHLBI NIH HHS; R37HL091102/HL/NHLBI NIH HHS; RC1 HL100891/HL/NHLBI NIH HHS; RC1HL100891/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cytokines; 147336-22-9/Green Fluorescent Proteins; EC 2.7.10.1/Proto-Oncogene Proteins c-kit; EC 2.7.11.1/PIM1 protein, human; EC 2.7.11.1/Proto-Oncogene Proteins c-pim-1
Comments/Corrections

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