Poor Functional Recovery After Transplantation of Diabetic Bone Marrow Stem Cells in Ischemic Myocardium

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

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1158-1165.e1
JournalJournal of Heart and Lung Transplantation
Volume28
Issue number11
DOIs
StatePublished - Nov 2009
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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