TY - JOUR
T1 - Poor Functional Recovery After Transplantation of Diabetic Bone Marrow Stem Cells in Ischemic Myocardium
AU - Govaert, Johannes A.
AU - Swijnenburg, Rutger Jan
AU - Schrepfer, Sonja
AU - Xie, Xiaoyan
AU - van der Bogt, Koen E.A.
AU - Hoyt, Grant
AU - Stein, William
AU - Ransohoff, Katherine J.
AU - Robbins, Robert C.
AU - Wu, Joseph C.
N1 - Funding Information:
This work was supported in part by grants from Burroughs Wellcome Foundation (J.C.W.), HL085899-02 (J.C.W.), the American Heart Association Medical Student Research Award (J.A.G.), the Netherlands Heart Foundation (J.A.G.), American Heart Association (J.C.W.), and grants from the University of Leiden (J.A.G.)
PY - 2009/11
Y1 - 2009/11
N2 - 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+/+Leprdb/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+/+Leprdb/J mice underwent left anterior descending artery ligation and were randomized into 3 groups receiving 2.5 × 106 diabetic BMMCs (n = 8), 2.5 × 106 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+/+Leprdb/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 μl/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.
AB - 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+/+Leprdb/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+/+Leprdb/J mice underwent left anterior descending artery ligation and were randomized into 3 groups receiving 2.5 × 106 diabetic BMMCs (n = 8), 2.5 × 106 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+/+Leprdb/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 μl/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.
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U2 - 10.1016/j.healun.2009.06.018
DO - 10.1016/j.healun.2009.06.018
M3 - Article
C2 - 19782602
AN - SCOPUS:70350072079
SN - 1053-2498
VL - 28
SP - 1158-1165.e1
JO - Journal of Heart and Lung Transplantation
JF - Journal of Heart and Lung Transplantation
IS - 11
ER -