Document Detail


Poor functional recovery after transplantation of diabetic bone marrow stem cells in ischemic myocardium.
MedLine Citation:
PMID:  19782602     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Autologous bone marrow mononuclear cell (BMMC) therapy has shown promise for improving cardiac function after myocardial infarction. The efficiency of such therapy for diabetic patients remains unknown.
METHODS: BMMCs were harvested from type 2 diabetic male BKS.Cg-m+/+Lepr(db)/J mice or C57BLKS/J (non-diabetic control) mice and were isolated using Ficoll-based separation. Cell characterization was performed by flow cytometry. Cell viability was determined by apoptosis and proliferation assays. Female BKS.Cg-m+/+Lepr(db)/J mice underwent left anterior descending artery ligation and were randomized into 3 groups receiving 2.5 x 10(6) diabetic BMMCs (n = 8), 2.5 x 10(6) control BMMCs (n = 8), or phosphate-buffered saline (n = 6). At Week 5, cardiac function was assessed with echocardiography and invasive hemodynamic measurements. Post-mortem cell survival was quantified by TaqMan real-time transcription polymerase chain reaction (RT-PCR) for the male Sry gene.
RESULTS: BKS.Cg-m+/+Lepr(db)/J BMMCs showed a significantly lower mononuclear fraction and a significantly lower proliferation rate compared with C57BLKS/J BMMCs. Fractional shorting (40.1% +/- 1.2% vs 30.3% +/- 1.9%; p = 0.001) and cardiac output (4,166 +/- 393 vs 2,246 +/- 462 microl/min; p = 0.016) significantly improved for mice treated with control BMMCs injection compared with those treated with diabetic BMMCs, respectively. This difference could not be attributed to difference in cell engraftment because TaqMan RT-PCR showed no significant difference in cell survival in infarcted hearts between the 2 groups.
CONCLUSIONS: Diabetic BMMCs are significantly impaired in their ability to improve cardiac function after myocardial infarction compared with control BMMCs. These findings could have significant clinical implication regarding autologous BMMC therapy in diabetic patients.
Authors:
Johannes A Govaert; Rutger-Jan Swijnenburg; Sonja Schrepfer; Xiaoyan Xie; Koen E A van der Bogt; Grant Hoyt; William Stein; Katherine J Ransohoff; Robert C Robbins; Joseph C Wu
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-26
Journal Detail:
Title:  The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation     Volume:  28     ISSN:  1557-3117     ISO Abbreviation:  J. Heart Lung Transplant.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-10-26     Completed Date:  2010-01-08     Revised Date:  2014-09-08    
Medline Journal Info:
Nlm Unique ID:  9102703     Medline TA:  J Heart Lung Transplant     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1158-1165.e1     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Bone Marrow Transplantation / methods*
Cardiovascular Diseases / surgery
Cell Survival
Coronary Vessels / surgery
Diabetes Mellitus, Experimental / surgery*
Diabetic Angiopathies / surgery*
Disease Models, Animal
Female
Humans
Male
Mice
Mice, Inbred C57BL
Mice, Inbred Strains
Myocardial Ischemia / surgery*
Reverse Transcriptase Polymerase Chain Reaction
Stem Cell Transplantation / statistics & numerical data*
Transplantation, Autologous / physiology*
Grant Support
ID/Acronym/Agency:
HL085899-02/HL/NHLBI NIH HHS; L30 HL085899/HL/NHLBI NIH HHS; L30 HL085899-02/HL/NHLBI NIH HHS
Comments/Corrections

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