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Stem cell mobilization therapy appears to be ineffective in repairing damage caused by myocardial infarction


Therapy that involved bone marrow stem cells did not improve cardiac function in patients following a myocardial infarction.
There has been increasing evidence that stem cells contribute to regeneration of cardiac tissue and the development of new blood vessels following a heart attack, thus opening up new prospects for stem-cell based therapies. Granulocyte colony-stimulating factor ( G-CSF, a growth-factor protein ) induces mobilization of bone marrow stem cells.

Dietlind Zohlnhöfer, of the Technische Universität, Munich, Germany, and colleagues conducted a randomized, double-blind, placebo-controlled study ( REVIVAL-2 ) to assess the value of G-CSF treatment in a large group of patients following a heart attack.
The 114 patients, diagnosed with ST-segment elevation acute myocardial infarction ( STEMI ), had successful reperfusion to the heart by percutaneous coronary intervention ( PCI ) within 12 hours after onset of symptoms.
Patients were randomly assigned to receive by injection either a daily dose of 10 µg/kg of G-CSF or placebo for 5 days.
The patients were treated between February 2004 and February 2005.

Treatment with G-CSF produced a significant mobilization of bone marrow stem cells. The researchers found that this did not alter infarct size or left ventricular function after a heart attack. " Moreover, in contrast to other studies, no increase in the risk of restenosis or major adverse cardiac events was observed with G-CSF treatment," the authors write.

" The REVIVAL-2 trial had a cohort that was larger than all 3 previous trials taken together and had a relatively long follow-up period based on sensitive assessment methods of left ventricular function and infarct size. In conclusion, use of G-CSF therapy to mobilize bone marrow–derived stem cell does not improve left ventricular recovery in patients with acute myocardial infarction after successful mechanical reperfusion," they write.

In an accompanying editorial, Robert A. Kloner, of the University of Southern California, Los Angeles, discusses the findings of Zohlnhöfer and colleagues.

" Even 3 to 6 hours after acute myocardial infarction, certain therapies still may benefit the heart. However, therapies aimed at recruiting stem cells and regenerating new myocardium remain experimental and have yet to be proven effective in large, long-term multicenter trials in which therapies are administered in a randomized, placebo-controlled, double-blind fashion and the size of the initial myocardial infarction and baseline cardiac function are taken into account.
The study by Zohlnhöfer et al yielded negative results and some investigators may be disappointed with these results or may try to find fault with the study."

" However, this investigation is one of the first, controlled, larger, and more carefully designed studies to assess the effect of an attempt to recruit stem cells to an acute myocardial infarction. Additional large, carefully designed trials are needed to assess the true potential ( or possibly lack of potential ) of stem cell therapy to treat acute myocardial infarction. … Only with such trials will it be possible to differentiate between the hype often generated by smaller, less well-controlled trials and reality."

Source: Journal of American Medical Association, 2006


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