|
anthracycline cardiotoxicity reversed with cardiac stem cells (in mice)!!
Anthracycline-Induced Cardiomyopathy Reversed in Rats Using Cardiac Stem Cells
In a rat model, researchers have reversed the cardiomyopathy often seen with anthracycline treatment, by using the animals' own cardiac stem cells, according to an online report in Circulation.
Dr. Piero Anversa from Brigham and Women's Hospital, Harvard Medical School, Boston, wondered whether doxorubicin's toxicity was in fact due to its effects on populations of stem cells now known to live in the heart.
"The adult heart in mammals, including humans, is a self-renewing organ regulated by a resident cardiac stem cell compartment and not a post-mitotic organ as claimed for the last 70 years," Dr. Anversa told Reuters Health.
Dr. Anversa and colleagues showed in vitro that the anthracycline doxorubicin promoted oxidative stress and the activation of p53, which together inhibited the growth and survival of cardiac progenitor cells.
Injecting rats with doxorubicin led to a cardiac myopathy in which myocyte death predominated and contributed to the deterioration of ventricular function, the authors report.
Doxorubicin also induced significant changes in global gene expression of cardiac progenitor cells, upregulating 103 genes and downregulating 21.
These effects had a negative impact on cell viability and growth, the researchers say, depleting the cardiac progenitor cell pool available for cardiac homeostasis and repair.
The team also cultured cardiac progenitor cells from rats before administering doxorubicin. When the cultured progenitor cells were injected into the failing myocardia of the anthracycline-treated rats, they reduced replacement fibrosis by 34% at 3 weeks and by 53% at 6 weeks.
The results indicated that cardiac progenitor cell differentiation partially restored the structural integrity of the cardiomyopathic heart, the authors note.
Indeed, in surviving animals, "cardiac function was largely restored by cardiac progenitor cell administration," the researchers said. They also report that myocardial regeneration reduced by more than half the extent of tissue damage associated with doxorubicin.
"The recognition that stem cells reside in the heart offers the possibility to introduce novel therapeutic strategies for the management of cardiac failure of various etiologies," Dr. Anversa said. "Cardiotoxicity may not be viewed any longer as an insurmountable problem for cancer patients."
Dr. Anversa's team now plans to use the technique in larger animals, as a step toward human trials.
"Although extreme caution must be exercised in the translation of these animal studies to human beings, the possibility is raised that myocardial biopsy samples may be obtained before antineoplastic drugs are given to cancer patients," the authors conclude. "Autologous cardiac progenitor cells can be isolated and expanded from these myocardial samples for the treatment of heart failure in individuals who are particularly sensitive to the cardiotoxicity of these chemotherapeutic agents."
Circulation 2010.
|
Linear Mode
