cells (CPCs) are implicated in the physiological turnover of myocytes, endothelial cells, smooth muscle cells, and fibroblasts. The recognition that the heart possesses a stem cell compartment that can regenerate myocytes and coronary vessels has raised the unique possibility to reconstitute dead myocardium after infarction; to repopulate the hypertrophic decompensated heart with new, better functioning myocytes and vascular structures; and perhaps to reverse ventricular dilation and wall thinning, restoring the physiological and anatomical characteristics of the normal heart. However, the field of regenerative cardiology is in its infancy and great caution has to be exercised in the implementation of this form of cellular therapy in human beings. Although there is no good animal model that can be employed to obtain this information, experimental evidence has been collected in Dr. Anversa’s laboratory in favor of the efficacy of CPCs for the repair of the damaged heart. Currently, cardiac-derived cells are utilized in clinical trials with encouraging results.
A fundamental discovery that has influenced the treatment of cardiac diseases in the world concerned the identification of a pool of bone marrow progenitor cells (BMPCs) capable of transdifferentiating into cardiomyocytes and coronary vascular cells. These findings have been furiously criticized, but they opened a new field of research in clinical cardiology. The therapeutic potential of BMPCs has been tested in several trials, which have documented that intracoronary and intramyocardial infusion of BMPCs is feasible and improves functional recovery in patients with acute myocardial infarction. Negative results have also been published. The substantial disparity among studies was analyzed by designing meta-analyses that involved subgroups of trials, in which one or more unifying parameters were identified: route of delivery, type of cardiac disease, age and gender of the patients, and presence of co-morbidities. Intracoronary injection of BMCs in patients with acute myocardial infarction was found to be safe and effective, with an average 3.79% increase in ejection fraction.
Dr. Anversa’s research has inspired generations of scientists.
Annarosa Leri
Harvard Medical School/Brigham & Women’s Hospital
See Also: Clinical Trials, U.S.: Heart Disease; Heart: Current Research on Isolation or Production of Therapeutic Cells; Heart: Development and Regeneration Potential; Heart: Existing or Potential Regenerative Medicine Strategies; Heart: Stem and Progenitor Cells in Adults; Heart Disease.
Further Readings
Angelini, Paolo and Roger R. Markwald. “Stem Cell Treatment of the Heart. A Review of Its Current Status on the Brink of Clinical Experimentation.” Texas Heart Institute Journal, v.32/4 (2005).
Anversa, Piero, Mark A. Sussman, and Roberto Bolli. “Molecular Genetic Advances in Cardiovascular Medicine. Focus on the Myocyte.” Circulation, v.109 (2004).
Orlic, Donald, et al. “Bone Marrow Cells Regenerate Infarcted Myocardium.” Nature, v.410 (April 5, 2001).
Arizona
Arizona
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Arizona
Arizona has one of the most conservative legislative bodies in the nation, and this conservative control is reflected in the state’s restrictive stem cell law that prohibits destructive human embryonic stem cell research and bans public funding for embryonic stem cell research. The law is widely attributed to the influence of the Center for Arizona Policy, an evangelical Christian organization that boasts having successfully lobbied for the passage of more than 120 bills, including several related to stem cell issues. Confronted with these restrictive measures, stem cell researchers in the state have continued their work by focusing on adult stem cells or stem cells taken from umbilical cord blood.
The Center for Arizona Policy
Despite the fact that Arizona voters are fairly evenly divided among Republicans (36 percent), Democrats (33 percent), and Independents (30 percent), in 2013 the state had a Republican governor and Republicans controlled both houses of the state legislature. Arizona Republicanism is not moderate. In 2014, Arizona Republicans publicly and formally censured John McCain, their Republican senior U.S. senator, for his liberal voting record, including his support of stem cell research. The voters censuring McCain are the same voters who have turned out in impressive numbers to see that the legislative initiatives of the Center for Arizona Policy (CAP) succeed. CAP is set up as a charity and thus can neither raise money for political candidates nor make endorsements, but so powerful is CAP President Cathi Herrod that she has been described as an unelected legislator, one who has unprecedented access to elected officials. CAP’s primary mission is to see that Arizona’s public policy protects the “sanctity” of human life “from its very beginning to its natural end.”
Although anti-abortion laws—more than 20 of them—have been the focus of CAP’s efforts, Herrod and her supporters have also targeted stem cell legislation. They use every opportunity to lobby, depending particularly on a well-organized church network. In advance of elections, they distribute a voting guide that identifies candidates’ stand on CAP issues, and they send “action alerts” to members during the legislative session, urging them to immediately call a legislator to be sure their senator or representative votes the right way. The result is voters who turn out to vote in large numbers, even in primary elections in which voter turnout is generally lower. Such tactics helped to pass the 2010 act that specifically makes illegal “any research that involves the disaggregation of any human embryo for the purpose of creating human pluripotent stem cells or human pluripotent stem cell lines.” CAP was also influential in seeing a 2006 bill passed that requires doctors to provide pregnant women with a pamphlet made available by the Department of Health Services that describes options related to umbilical cord blood donations and provides specific information on preservation and donation of cord blood.
Research Institutions
Researchers in Arizona avoid issues of legality and thorny ethical dilemmas by focusing on research that uses stem cells taken from umbilical cord blood or adult stem cells taken from fat tissue.
The University of Arizona, established in 1885, is a public research university ranked among the top public universities and colleges in physical sciences research and in research and development expenditures by the National Science Foundation. David Harris, a professor in the university’s Department of Immunobiology, is considered a pioneer in stem cell banking. In 1991, Harris became among the first to bank stem cells when he preserved his first child’s cord blood stem cells. In 1992, Harris founded the Arizona Cord Blood Bank, which later became the Cord Blood Registry, the largest cord blood stem cell bank in the world.
Lalitha Madhavan, MD, PhD, and assistant professor of neurology, concentrates on stem cells and their applications to neurological diseases with a goal of devising brain repair strategies for neurological disorders based on the manipulation of stem cells. Zain Khalpey, director of mechanical circulatory support, health transplant, and translational research at the university’s Sarver Heart Center and practicing cardiothoracic surgeon at the University of Arizona Medical Center, is engaged in research that uses stem cells in ex vivo reconditioning of marginal human hearts and lungs, which will generate functional lung and heart tissue that ultimately can be used for transplantation.
Arizona State University (ASU), a multicampus public research university, is ranked among the best in the nation in terms of research output, innovation, development, expenditures, number of awarded patents, and awarded research grant proposals. Karmella Haynes, an assistant professor in the School of Biological and Health Systems Engineering, one of the Ira A. Fulton Schools of Engineering at ASU, is a synthetic biologist whose research includes development of a synthetic protein that is able to control gene expression and slow the growth of cancer cells. Haynes, an affiliate researcher for the Synthetic Biology Engineering Research Center (SynBERC), which is supported by the National Science Foundation (NSF), was awarded an $81,000 NSF grant in 2013 to support