NEW YORK (Reuters Health), Dec 24 - Intramyocardial transfer of cord blood-derived stem cells improves left ventricular function and prevents scar formation in a porcine model of acute MI, German investigators report in the January issue of Heart.
Because no long-term myocardial engraftment of donor stem cells occurs, the authors propose that cardiac structure and function are maintained by "preservation of existing recipient myocardium via paracrine effects."
Senior author Dr. Arjang Ruhparwar, at the University of Heidelberg, and co-investigators chose to use human cord blood-derived unrestricted somatic stem cells because of their relatively low immunogenicity, their high levels of pluripotency and expansion potential, and their ability to release "a multitude of cytokines."
Immediately after ligature of the coronary artery of month-old domestic pigs treated with immunosuppressants, the scientists injected cultured cord-blood stem cells (10 animals) or culture medium (right animals) into the free wall of the left ventricle.
After 48 hours, there was no difference between groups in apoptosis, recruitment of macrophages, or mitosis, and after eight weeks, the authors detected no evidence of donor cell engraftment. Thus, they exclude the theory that "functional recovery is simply based on improved neovascularization or modified tissue remodeling."
Eight weeks post-MI, transesophageal echocardiography showed that the "left ventricular ejection fraction had dramatically improved" in stem cell-treated animals, recovering to 88% of baseline levels, whereas ejection fraction remained severely impaired at 45% of pre-MI levels in control animals.
Left ventricular end diastolic volume significantly increased in the control animals, and there was significant scarring in the infarction areas. By contrast, there was no evidence of scarring or ventricular dilation in the pigs treated with stem cells.
"It appears not unlikely," Dr. Ruhparwar and colleagues write, "that unrestricted somatic stem cells, which have been shown to release a variety of cytokines, can directly support myocardial preservation or regeneration."
They speculate further that the elastic properties of the injected stem cells reduce wall tension and prevent additional myocardial ischemia during diastole, thereby inhibiting left ventricular dilation and preserving left ventricular geometry.
Heart 2009;95:27-35.
Last Updated: 2008-12-24 8:00:46 -0400 (Reuters Health)
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