Autologous Culture-Modified Mononuclear Cells Could Enhance Vascular Repair
Delivering culture-modified mononuclear cells to the site of injury in arteries that have been injured by balloon (mimicking injuries from percutaneous interventions) could present a new method of vasoprotection, said researchers from the Mayo Clinic in Rochester, Minn, in a report in the September 23, 2003, issue of the journal Circulation (Circulation. 2003;108:1520–1526).
The researchers, led by Rajiv Gulati, MD, of the Mayo Clinic, cultured rabbit peripheral blood mononuclear cells in endothelial growth media to produce highly proliferative cells with a phenotype similar to that of endothelial cells. Rabbits with balloon carotid injuries immediately received autologous culture-modified mononuclear cells or buffered saline solution. Four weeks after the delivery of the culture-modified mononuclear cells, fluorescence-labeled mononuclear cells were detected in all vessel layers in the treated animals. Animals that received the culture-modified mononuclear cells showed more endothelialization than did those who received the saline solution. The treatment with the culture-modified cells also reduced neointimal formation by 55% at 4 weeks compared with the saline-treated animals.
The authors wrote, “The results reported here show that the effect of CMMC [culture-modified mononuclear cell] delivery is an overall reduction in cellular accumulation. This reduction may be mediated in part by accelerated restoration of an endothelial barrier. It is also conceivable that the provision of supplementary sources of NO [nitric oxide] and other secreted factors deeper in the vessel wall may suppress activation and recruitment of additional plaque-forming cells. . . . Overall, the findings reported in this study expand the potential applications of cell therapy to direct modulation of vascular responses to injury. Furthermore, they have implications for gene therapy and tissue engineering approaches to vascular disease.”
Cardiac Stem Cells—A Potential Therapeutic Bonanza
The adult heart may consist mostly of terminally differentiated cells, but researchers from the New York Medical College in Valhalla and the University of Florida at Gainesville report in the September 19, 2003, issue of the journal Cell (Cell. 2003;14:763–776) that Lin_ c-kitPOS cells have the properties of cardiac stem cells.
The cells, they said, self-renew and are clonogenic and multipotent. They give rise to myocytes, smooth muscle cells, and endothelial cells. The authors noted that c-kitPOS cells colonize the embryonic yolk sack, liver, and probably other organs. In a series of elegant animal experiments, the researchers identified the putative stem cells in the animal hearts at a rate of approximately 1 Lin_ c-kitPOS cell for every 10 000 cells. The team, led by Piero Anversa, MD, of New York Medical College, used a series of cell surface makers found on stem cells in other parts of the body that helped identify potential stem cells in the heart. When these cells were grown in lab culture, they developed into myocytes, smooth muscle cells, and endothelial cells. When the putative stem cells were injected into the damaged heart muscles of rats, the heart grew new tissue and functioned better.
“Now that we have identified where the stem cells reside, we are developing strategies to mobilize them to migrate to the damaged cardiac site,” said Dr Anversa in a released statement.
In an accompanying commentary, Leslie A. Leinwand, PhD, of the Department of Molecular, Cellular, and Developmental Biology at the University of Colorado in Boulder, said, “the study provides convincing evidence that there is a stem cell population that resides in the adult heart. The stem cells can be isolated and expanded in culture indefinitely” (Cell. 2003;14:658–659).
Dr Leinwand noted some reservations about the findings, as well. “Multipotent adult progenitor cells, or MAPCs, which have also been shown to have cardiogenic potential, are characterized as being negative for the marker (c-Kit) used to define the cells in the Beltrami et al study. In addition, the fact that the adult stem cells in this study can form endothelium, smooth muscle, and cardiac muscle is confounding, since these three cell types arise from three different cell lineages. Finally, if these cells exist and lie dormant in the heart, why do they not mobilize and divide in response to an injury? The answers to these questions will certainly make for some interesting biology and perhaps future therapies.”
Melatonin—Not for Everyone
Melatonin, a dietary supplement touted for overcoming the turmoil of jet lag and insomnia, may be dangerous for patients with orthostatic intolerance, according to a Penn State College of Medicine researcher in the September 15, 2003, issue of the Journal of Physiology (J Physiol. 2003;551:1043–1048).
Chester A. Ray, PhD, an associate professor of medicine at the Hershey, Pa, medical school, gave 12 healthy volunteers either 3 mg melatonin tablet or placebo. After 50 minutes, the volunteers were told to lie down and place both legs in a lower-body negative-pressure chamber that reduces pressure to the legs, which mimics the effect of standing up.
Dr Ray recorded the sympathetic nerve activity to blood vessels of the leg muscle by microneurography. First, measurements were taken with the volunteers at rest. Then, the pressure in the chamber was decreased and the measurements were taken again. The nerve activity when volunteers were under orthostatic stress was lower in volunteers who took melatonin compared with those who received placebo.
“This finding suggests that melatonin has specific physiological effects, namely, decreasing nerve activity, when someone stands, but not necessarily during other types of physical activities,” Dr Ray said.
European Society of Cardiology Awards Gold Medal to Dr Hatle
Liv Kristin Hatle, MD, Professor of Medicine at the Norwegian University of Technology and Science in Trondheim, Norway, received the European Society of Cardiology (ESC) Gold Medal at its recent Congress in Vienna, Austria. Dr Hatle was recognized for her seminal research in the field of ultrasound and echocardiography that began in the 1970s.
Dr Hatle graduated from the University of Oslo, Norway, in 1961 and obtained postgraduate education in cardiology and internal medicine at Trondheim University Hospital in Norway. She began her clinical and research career at the same hospital where she served as consultant cardiologist and Professor of Medicine from 1974 until 1990. In 1996, she served as Professor of Cardiology at the University of Linkoping, Sweden, and from 1999 to 2001 as Visiting Professor at Leuven, Belgium.
She has been a member of the editorial board of the European Heart Journal, as well as reference scientific journals in the fields of ultrasound and echocardiography. She is an honorary member of the American Institute of Ultrasound in Medicine and past chairperson of the Working Group on Echocardiography of the ESC. She has delivered the Laennec Society Lecture at the American Heart Association Scientific Sessions, as well as the Grüntzig Lecture of the ESC. She has also received the American College of Cardiology Presidential Citation. She has published more than 100 scientific papers in peer-reviewed journals, 20 book chapters, and a textbook on cardiac Doppler ultrasound.
Four scientists who delivered Special Lectures at the Annual Congress in Vienna received ESC Silver Medals.
Jos R.T.C. Roelandt, MD, head of the Division of Cardiology at the Thoraxcentre at Erasmus University in Rotterdam, the Netherlands, delivered the Denolin Lecture, titled “Ultrasound: The Stethoscope of the Third Millennium?” Dr Roelandt has served on the editorial boards of several major cardiology journals and authored more than 1000 scientific papers. He is currently editor-in-chief of the European Journal of Echocardiography.
Amadeo Betriu, Professor of Medicine at the University of Barcelona in Spain, delivered the Grüntzig Lecture, titled “Role of Percutaneous Coronary Intervention in the Treatment of Acute Myocardial Infarction.” Dr Betriu’s main interests are interventional cardiology, the pathophysiology of acute coronary syndromes, and reperfusion. He has served as principal investigator of several landmark trials and is the author of more than 100 peer-reviewed journal articles.
Salim Yusuf, MD, Professor of Medicine at McMaster University in Hamilton, Ontario, Canada, delivered the ESC Lecture on Population Sciences, titled “Tackling the Global Burden of Cardiovascular Disease.” Dr Yusuf has established an international program of research in cardiovascular diseases and population science at McMaster. He is the author of more than 450 articles.
Paul M. Vanhoutte, MD, PhD, of the University of Hong Kong, delivered the ESC Lecture on Basic Science, titled “Endothelial Dysfunction and Coronary Disease.” He is an honorary member of several scientific societies in the fields of physiology and pharmacology on both sides of the Atlantic and a member of the editorial board of the most important scientific journals. He is the author of more than 500 original research papers and more than 450 reviews or chapters in books. His major scientific contribution has been in the field of endothelial cells in the control of the underlying vascular smooth muscle in health and disease.