Transfer of Bone Marrow Progenitors Prevents Coronary Insufficiency and Systolic Dysfunction in the Mechanical Unloaded Heart in Mice

Koike, Masato; Kojima, Hideto; Fujimiya, Mineko; Matsubayashi, Keiji; Aimi, Yoshinari; Kimura, Hiroshi; Asai, Tohru

doi:10.1016/j.jss.2010.01.042

« Previous Next »Journal of Surgical Research
Volume 171, Issue 1 , Pages 47-57, November 2011

Transfer of Bone Marrow Progenitors Prevents Coronary Insufficiency and Systolic Dysfunction in the Mechanical Unloaded Heart in Mice

Masato Koike, M.D
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
- Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
Hideto Kojima, M.D., Ph.D.
- Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
- To whom correspondence and reprint requests should be addressed at Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Tsukinowacho, Seta, Otsu, Shiga 520-2192, Japan.
Mineko Fujimiya, M.D., Ph.D.
- Department of Anatomy, Shiga University of Medical Science, Otsu, Shiga, Japan
Keiji Matsubayashi, M.D., Ph.D.
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan
Yoshinari Aimi, M.D., Ph.D.
- Department of Anatomy, Shiga University of Medical Science, Otsu, Shiga, Japan
Hiroshi Kimura, Ph.D.
- Department of Molecular Genetics in Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan
Tohru Asai, M.D., Ph.D.
- Department of Surgery, Shiga University of Medical Science, Otsu, Shiga, Japan

Received 15 October 2009 published online 24 February 2010.

Background

Left ventricular-assist device (LVAD) can lead to improvement of cardiac performance in a subset of patients, but chronic mechanical unloading in this fashion may result in left ventricular (LV)-atrophy and impaired functional recovery. Here, we evaluate the efficacy of transferring bone-marrow KSL cells (Lin-/c-kit+/Sca1+), a fraction containing endothelial progenitor cells, for preventing LV-atrophy and malfunction in a mouse model of mechanical unloading of the heart.

Materials and Methods

Recipients of an isogenic heart transplant received intramyocardial isogenic KSL cells or PBS in three different locations of the left ventricle (LV). Coronary blood flow and LV systolic function were evaluated by echocardiography, and morphologic changes were analyzed on d 7 and 56.

Results

PBS-treated mice showed severe systolic dysfunction and large thrombi in LV at both time points. In contrast, KSL cell transfer markedly reduced systolic dysfunction and thrombus size. Furthermore, in comparison with PBS control, KSL recipients had increased coronary blood flow (3-fold, P < 0.01) accompanied by increased LV capillary density and muscle mass.

Conclusions

These results indicate that intramyocardial transfer of bone marrow KSL cells significantly protects against coronary insufficiency and systolic dysfunction in the chronic LV-unloading heart, suggesting that this approach may have clinical potential as a combination therapy with LVAD.

Key Words: LVAD, KSL cell, heterotopic heart transplantation, coronary circulation, echocardiography, CD31, bone marrow stem cells