Cardiopulmonary support and physiology
Cell transplantation preserves cardiac function after infarction by infarct stabilization: Augmentation by stem cell factor

Read at the C. Walton Lillehei Resident Competition at the Eighty-fifth Annual Meeting of The American Association for Thoracic Surgery, San Francisco, Calif, April 10-13, 2005.
https://doi.org/10.1016/j.jtcvs.2005.07.012Get rights and content
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Objective

We hypothesized that implantation of adult mesenchymal stem cells after acute myocardial infarction mobilizes bone marrow precursor cells by activating the stem cell factor pathway, and that overdriving this pathway would enhance the beneficial effects of cell transplantation.

Methods

After coronary ligation, medium, mesenchymal stem cells, or stem cell factor–overproducing mesenchymal stem cells were injected into the anterior left ventricle. Cells from β-galactosidase transgenic mice enabled tracking of injected cells. The global and local impact of the cells was evaluated by measuring cytokine levels, endothelial progenitor cells, and myocardial angiogenesis, and by addressing cardiomyogenesis with confocal microscopy. The impact on cardiac function was evaluated by pressure-volume loops. Ventricular morphometrics were measured after in situ perfusion-fixation of the hearts at physiologic pressures.

Results

Implantation of mesenchymal stem cells increased myocardial stem cell factor levels 2.0-fold, endothelial progenitor cell mobilization 2.7-fold, and myocardial angiogenesis 2.3-fold (P < .05), but did not induce mitogenesis in host cardiomyocytes or give rise to β-galactosidase–expressing cardiomyocytes. Cell-transplanted groups had improved indices of cardiac function, including preload recruitable stroke work and end-systolic elastance (P < .001). Cell transplantation resulted in 2.0-fold smaller ventricular volumes (P = .001) and 2.0-fold reduced infarct scar area (P = .056), but had no effect on the volume of spared myocardium. Stem cell factor overproduction imparted greater functional benefit without inducing detectable histologic cardiomyocyte regeneration.

Conclusion

Mesenchymal stem cell implantation after myocardial infarction facilitates functional cardiac regeneration without myocyte regeneration through augmentation of endogenous infarct repair, which is enhanced by stem cell factor.

Abbreviations and Acronyms

CD
cluster of differentiation
EPC
endothelial progenitor cell
LV
left ventricle
MI
myocardial infarction
MSC
mesenchymal stem cell
PECAM
platelet endothelial cell adhesion molecule
SCF
stem cell factor

CTSNet classification

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This work was supported by operating grants from the Canadian Institute of Health Research (CIHR MOP14795) to R.K.L. and S.F., Heart and Stroke Foundation (HSF T5287) to R.D.W. and S.F., and the Physician Services Incorporated Foundation (R04-23) to S.F. and T.M.Y. S.F. is a CIHR and joint CIHR/HSF TACTICS Research Fellow and a Medical Scientist Training Fellow of the McLaughlin Centre for Molecular Medicine.