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Reduced mitochondrial respiration and improved coupling in infarcted heart following stem cell therapy
Author(s) -
Hughey Curtis,
Ma Lianli,
James Freyja,
Young Pampee Paul,
Wasserman David,
Rottman Jeff,
Shearer Jane
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.660.2
Subject(s) - respiration , stem cell therapy , stem cell , cellular respiration , medicine , myocardial infarction , mitochondrion , cardiology , mesenchymal stem cell , chemistry , biology , biochemistry , pathology , anatomy , microbiology and biotechnology
Aim To determine the changes in mitochondria following stem cell therapy in the infarcted heart. Methods C57BL/6J mice were randomly divided into three treatment groups, SHAM (n=8), MI (myocardial infarction)(n=9) and MI‐STEM (n=8) receiving direct myocardial injection of mesenchymal stem cells. Echocardiography was performed at baseline, 1 and 3 wk post‐infarct. Mitochondrial respiration (pmol/s*mgww/IUCS) in permeabilized fibers bordering the infarct was determined at 4wk following treatment. State 2 (absence of ADP) respiration, state 3 (ADP‐stimulated) respiration and state 4 respiration were examined. Citrate synthase activity (CS) was determined. Results MI‐STEM state 2 was lower than the MI and SHAM groups (20.98 vs. 29.46 and 32.45). State 3 was lower in the MI and MI‐STEM groups compared to the SHAM (77.01 and 68.46 vs. 97.18). Respiratory Control Ratio (RCR) was higher in the MI‐STEM compared to MI group (3.37 vs. 2.71) and state 4 was lower in the MI‐STEM compared to the SHAM group (67.93 vs. 96.23). Conclusion Cell therapy does not prevent declines in state 3 respiration, however, the higher RCR and lower state 4 respiration suggests stem cell treatment reduces futile respiration and increases respiration efficiency. These findings show cell therapy to improve cardiac function by reducing the energetic mismatch between supply and demand following a MI. Research supported provided by CIHR.