Heart Disease Treatment with Stem Cells
Heart failure and heart attack, also known as myocardial infarction, are both associated with high rates of morbidity and mortality, and previously there have existed very few and very limited therapeutic options for either of these conditions. In the past, there has not been any treatment for reversing cardiac scar tissue, nor for regenerating the cardiac tissue that is damaged from a heart attack.
Today, however, such a treatment does exist. Such regeneration is now possible, as a result of recent advances in stem cells therapy.
A growing number of studies have demonstrated that specialized myocardial cells may be regenerated by stem cells. Even certain types of adult stem cells have been shown to differentiate into cardiac cells and repair cardiac tissue.
Perhaps one of the most dramatic examples of this was seen in a 16-year-old boy who received stem cell therapy after accidentally shooting himself in the heart with a nail gun. The treatment successfully saved his life and restored his heart function to normal. As first reported by the Associated Press on March 7th of 2003, the boy suffered a massive heart attack while undergoing open-heart surgery to repair the injuries sustained in the nail gun accident. Suddenly faced with the necessity of a heart transplant, the boy instead became the first human in the U.S. to receive stem cells in an attempt to repair damaged cardiac tissue. Dr. William O'Neill, Chief of Cardiology at the William Beaumont Hospital in Royal Oak, Michigan, led the experimental procedure, which began with a four-day regimen of a drug that stimulated the boy's natural production of his own stem cells. After harvesting the boy's stem cells from his blood, the doctors then used a catheter to transplant the stem cells into the main artery that supplies blood to the heart. Despite the fact that the entire front wall of tissue in his heart was dead, the boy was discharged a week later to recuperate at home. This case represents an unprecedented restoration of cardiac function following severe injury, and a landmark accomplishment in the development of stem cell therapy.
Certainly one of the most remarkable aspects of this incident is the fact that the boy was not treated with embryonic stem cells, but with his own stem cells, harvested from his own blood. In fact, a number of studies have involved the use of stem cells derived from adult blood, which increasingly shows great promise in the treatment of damaged cardiac tissue.
In October of 2003, researchers at the M.D. Anderson Cancer Center in Houston reported results of an animal study in which adult stem cells derived from blood had regenerated damaged heart muscle. The results were published in the journal Circulation. According to Edward T.H. Yeh, M.D., professor and chair of the Department of Cardiology at M.D. Anderson,
"This takes us a big step ahead. Taking stem cells from blood is a lot easier, and a lot less painful, than taking it from bone marrow. For patients, it would be as simple as donating blood. We would then isolate these potent cells and give them back to the patient where the damage has occurred."
Although the study was conducted in mice, the results indicate that stem cells circulating in the blood can regenerate different organ systems as needed. While studies abound which demonstrate the ability of bone marrow-derived stem cells to regenerate cardiac tissue, this was one of the first studies to demonstrate that ordinary adult human blood also possesses that ability. The researchers consisted of cardiologists and oncologists who were interested in treating the heart failure that occurs in approximately 10% of chemotherapy patients, and their supply of stem cells came from a widely available source. During the process of collecting and banking human red blood from donors, a certain amount of "debris" is generally discarded, which consists primarily of the white blood cells after they have been separated from the red blood cells. For this study, the researchers collected their stem cells from this discarded "debris", and from these white blood cells they then isolated those cells that express a protein known as CD34+ which identifies the cells as stem cells. These human cells were then injected into mice after heart attacks had been induced in the animals. The researchers then observed that new cardiomyocytes (heart muscle cells) had developed at the edge of the damaged tissue in the mice, along with several layers of new endothelial (blood vessel) and smooth muscle cells.
Being able to use peripheral blood as a source of stem cells sets a new precedent. As Dr. Yeh has said,
"We've shown that CD34+-associated cells can actually transform into three different cells used by the heart. This study demonstrates that adult blood stem cells may be an alternative to these other sources of cells for myocardial regeneration. And blood is a readily available source of stem cells that does not require significant manipulation."
Many of the experiments that have been conducted in the realm of cardiac regeneration have involved the use of nonhuman mammalian embryonic stem cells. One such study, as reported in the August 2004 issue of the American Journal of Physiology, reported that researchers at the Mayo Clinic successfully used embryonic rodent stem cells to regenerate heart muscle in mice. The researchers had injected embryonic rodent stem cells into the injured heart muscle of rats in whom myocardial infarction had been induced. The transplanted stem cells were then found to differentiate into heart cells that integrated with the surrounding muscle. Improved heart function was seen within 3 weeks, most noticeably within the areas of damaged tissue, and this improved function did not diminish over the 12-week follow-up period. There was no evidence of arrhythmias (abnormal heart rhythms), and the animals exhibited a superior response to stress when compared to those animals who had not been treated with stem cells. According to Andre Terzic, M.D., Ph.D., a specialist in cardiac biology who led the study,
"The heart has a limited capacity for self-repair. However, based on our experimental findings, embryonic stem cells present an opportunity for reparative therapy with stable benefit in myocardial infarction."
It has since been established, however, that the same benefits may be obtained from non-embryonic sources of stem cells, such as from blood-derived stem cells.
In an attempt to discern precisely what it is that happens at the cellular level during a heart attack, researchers at the Utrecht University in the Netherlands studied the particular membrane changes that occur during a heart attack in order to trace the process by which these changes lead to cellular death. They found that the phospholipids in a healthy cell are asymmetrically distributed across the two layers of the surrounding shell, but during a heart attack, however, this particular type of asymmetrical distribution is partially disrupted. The researchers also found that the number of lipids in the outer layer of the membrane increases as lipids migrate from the inner to the outer layer during a heart attack, while calcium ions usually migrate from the outer to the inner layers of the cell. This imbalance in phospholipid and calcium content is believed to play a major role in the processes that damage heart muscle during a heart attack. If "reperfusion" (the restoration of blood flow after a heart attack) occurs quickly, tissue can be saved, otherwise reactive oxygen causes damage to the fatty acid tails of the lipids, which in turn triggers the cellular death of cardiac muscle tissue and the formation of scar tissue.
As previously mentioned, a number of studies have focused on bone marrow-derived adult stem cells in the regeneration of heart tissue following a heart attack. Generally, it has been observed by multiple independent investigators that circulating endothelial progenitor cells (CPCs) derived from bone marrow are capable of differentiating into cardiomyocytes, and may be used as an effective therapy in improving neovascularization and left ventricular (LV) function. Since it is typically compromised after an acute myocardial infarction, left ventricular function is often used as a measure of the extent of heart damage - and, in stem cell therapy, as a measure of improvement in cardiac function.
Indeed, bone marrow is a particularly rich source of stem cells. In numerous animal experiments, researchers have found that bone marrow-derived mesenchymal stem cells (MSCs) migrate to the sites of damaged heart tissue when simply introduced into the blood stream, where they then mature and replace the dead scar tissue with new tissue that appears to be healthy and normal. In pigs, cardiac scar tissue was reduced in this manner by 50% within two months of the stem cell treatment.
In November of 2003, as reported at a conference of the American Heart Association, adult bone marrow-derived stem cells of a previously unidentified lineage were used to regenerate cardiac blood vessels in an animal model. After heart attacks had been induced in rats, the new, human bone marrow-derived multipotent stem cells (hBMSC) were then injected into the damaged regions within the animals' hearts. According to Young Sup Yoon, M.D., Ph.D. of Tufts University School of Medicine,
"This study is exciting because it is the first to show that human bone marrow includes a clonal stem cell population that can differentiate into both vessels and heart muscle. These cells can regenerate the essential tissues of the heart."
These stem cells did not belong to any previously known population of bone marrow-derived stem cells; they were not from hematopoietic cells, nor from mesenchymal cells, nor from stromal cells, yet they were shown to differentiate into all three of the so-called "germ layers." Once transplanted into the animals, the hBMSCs were found to differentiate into cardiac muscle and blood vessel cells. Additionally, the researchers also observed the expression of beneficial angiogenic cytokines, which encourage blood vessel growth, and of "cardiac transcription factors", which are important to the development of the heart in utero.
In November of 2000, Canadian researchers reported at a conference of the American Heart Association that they had successfully created new cardiac muscle from bone marrow-derived stem cells in an animal study. The researchers harvested mature stromal stem cells from the bone marrow of laboratory rats, and then injected those stem cells into the animals' hearts, after the animals had experienced heart attacks. The stromal cells were then found to differentiate into new heart muscle in 20 of the 22 rats that received this stem cell treatment. According to Ray C.J. Chiu, M.D., Ph.D., professor and chairman of the Division of Cardiothoracic Surgery at the McGill University Health Centre in Montreal, who led the study,
"When heart cells die, they are permanently lost. Heart failure is the death of functioning heart muscle. In the classic view of science, bone marrow had only one function: to replace red cells and white cells in the blood. The stromal cells were thought to be there just to support the production of blood cells. Only in the last couple of years did we recognize definitely that these marrow stromal cells are adult stem cells. The goal of our study is to replace those dead [cardiac] cells with new heart muscle cells. Marrow stromal cells are extremely promising. Four weeks after being injected, the [rats'] cells had heart muscle protein."
This study holds great promise for human therapy. Because this particular type of stem cell would be harvested from the patient, there would be no possibility of immune rejection, and no need for expensive immuno-suppressing medication.
In February of 2005, as reported in the Journal of Clinical Investigation, researchers at Tufts University reported the use of a "subset" of stem cells derived from human bone marrow in the regeneration of cardiac tissue following a myocardial infarction in rodents. Dr. Douglas Losordo and colleagues reported being able to differentiate these human bone marrow-derived stem cells into a variety of different cell types, which were then transplanted into a rat model of myocardial infarction. The human cells stimulated the release of growth factors and anti-apoptotic (programmed cell death) agents which in turn increased the proliferative potential of the cardiomyocytes in the animals. The net result was not only a regeneration of cardiac tissue but also the formation of new blood vessels that are necessary in cardiac repair.
As reported in the June 1st, 2001 issue of the Journal of Clinical Investigation, researchers at the Baylor College of Medicine in Texas also successfully demonstrated the ability of bone marrow-derived stem cells to regenerate tissue damaged from cardiac infarction. Led by Drs. Margaret Goodell and Karen Hirschi of the Center for Cell and Gene Therapy and the Department of Pediatrics at Baylor, the research team extracted stem cells from the bone marrow of one mouse, and, after purifying the cells through a sorting technique that Dr. Goodell had developed, the researchers then "tagged" the cells with a blue marker and transplanted them into the bone marrow of other mice suffering from heart attacks which had been induced by temporary coronary blockages. After 2 weeks, the marked stem cells were found in both the blood vessels and the cardiac muscle of the mice who had had heart attacks, but not in healthy mice who had not had heart attacks, and who had also been injected with the stem cells. According to Dr. Goodell,
"The body's natural response to injury is to repair itself. By letting the cells move into the blood stream, we've shown that the transformation of the bone marrow stem cells into blood vessels and heart tissue is part of a naturally occurring process."
Open heart surgery is necessary when stem cells are injected directly into the heart. The use of the blood stream as the means of delivery for stem cells to damaged heart tissue is highly preferable, since it avoids the possibility of infections and other complications from surgery. As Dr. Goodell explained,
"Ultimately, we want to develop targeted therapy, taking the patient's own stem cells to repair damaged tissue while preventing rejection. But first, we need to understand the mechanism - how stem cells turn into heart or vessel cells - and improve on that to make it more efficient. We want to direct that development."
While numerous animal studies have demonstrated the successful treatment of damaged cardiac tissue with stem cells, an increasing number of studies conducted on humans are also showing promising results. Some of these studies are listed herein.
Mesenchymal stem cells (MSCs), which are merely one type of stem cell derivable from adult bone marrow, were already known to mature into cartilage, fat, bone, tendons and muscle, prior to the discovery that they may also differentiate into cardiac cells. Researchers at Johns Hopkins University have thus conducted the first clinical trials in the U.S. in which adult MSCs were used to repair cardiac muscle damaged by a heart attack. While previous animal studies have demonstrated that MSCs are capable of maturing and replacing cardiac scar tissue that develops after a heart attack, this is considered to be the first such clinical trial involving humans.
In January of 2005, the American Heart Association published the results of a study in which researchers at the Texas Heart Institute at St. Luke's Episcopal Hospital in Houston successfully treated chronic cardiac ischemia (constriction or obstruction of the blood supply) with bone marrow-derived stem cells. The mesenchymal stem cells (MSCs) had already been successfully used as a treatment for acute ischemic heart disease, but this was the first study to demonstrate the effectiveness of the cells as a treatment for chronic ischemia. This new study found that MSCs differentiate into smooth muscle and endothelial cells, thereby promoting neovascularization and the improvement of myocardial perfusion and contractility. In the past, end-stage ischemic heart disease has typically been fatal and untreatable, but studies such as this indicate that a reversal of damaged tissue, even in this extreme condition, is now possible.
One of the first reports that mesenchymal stem cells (MSCs) are capable of repairing heart muscle came in March of 2003, when an article in Circulation: Journal of the American Heart Association announced that doctors at the Mayo Clinic in Rochester, Minnesota, had accidentally made the discovery. Four female patients with leukemia, who had survived 35 to 600 days after receiving bone marrow transplants from male donors, were examined by autopsy which revealed that some of their heart tissue contained male genetic material. The cardiomyocytes containing the Y chromosome had therefore originated from the male donors. This was the first confirmation that progenitor cells from outside the heart are capable of growing into new heart muscle. According to Noel Caplice, M.D., who led the study,
"Until recently, the heart has been seen as an organ that cannot be healed. Heart attack damage to the myocardium, or heart muscle, was considered irreversible. This study points the way to a process that could lead to heart repair."
In January of 2006, researchers in Belgium announced in the journal The Lancet a major breakthrough which they had made in the treatment of patients with acute myocardial infarction. By treating each patient with his or her own bone marrow-derived stem cells, the doctors found that they could reduce the size of each patient's infarction. In the standard double-blind, placebo-controlled study, 67 patients who had been stricken with acute myocardial infarction were examined. The study involved a large collaboration among cardiologists, hematologists, and nuclear radiologists from the Flanders Interuniversity Institute of Biotechnology, from the Catholic University of Leuven, the University Hospital in Gasthuisberg and the Stem Cell Institute in Leuven (SCIL). Together, the large team of researchers monitored changes in left ventricle physiology, blood supply and general heart metabolism. They found that improvements in the left ventricle were comparable in both the control group (who had been injected with a placebo) and the group who received the stem cells; but a significant improvement in overall "global" cardiac function was found in the subgroup of patients who had suffered the most serious infarctions. Additionally, in the group who had received the stem cells, the size of the infarct was significantly reduced.
A study conducted by researchers in Germany involved patients who had undergone successful angioplasty and stenting to restore blood flow in the coronary artery. Half of the group was then given bone marrow-derived stem cells while the other half received the best conventional treatment. The patients who received the stem cells showed a 6.7% improvement in left ventricular function as compared to only 0.7% in the other group.
In France, doctors treated a patient suffering from heart disease with stem cells derived from the patient's own skeletal muscle. After implanting the stem cells into the patient's heart, the doctors observed a successful reversal of the patient's condition.
A similar study in Brazil also demonstrated notable improvement in heart function after implantation of the patients' own stem cells following a heart attack.
As reported in the Journal of the American Heart Association in November of 2001, researchers in Japan reported success in regenerating cardiac tissue in patients with otherwise untreatable coronary artery disease. Kimikazu Hamano, M.D. and colleagues at the Yamaguchi University School of Medicine in Ube, Japan, used bone marrow-derived stem cells to improve the flow of blood in damaged coronary arteries. In an ongoing clinical trial, five patients received injections of their own bone marrow-derived stem cells into the affected arteries. According to Dr. Hamano,
"We found this new treatment to be safe, and we believe it could be an alternative treatment for heart patients who cannot be helped by coronary artery bypass surgery or balloon angioplasty."
The five patients had an average age of 66, and all of them suffered severe and debilitating angina (chest pain). Although they were all scheduled for bypass surgery, they were chosen to participate in this study because certain areas of their heart muscles had been identified as untreatable by surgery. As bypass surgery began on each patient, bone marrow was withdrawn from the hip, from which mononuclear cells were then harvested and later injected directly into the heart muscle. Depending on the size of the area of tissue to be treated, patients received between 5 and 22 injections of stem cells into their heart muscles. One month after surgery, each patient was examined by a nuclear medicine test known as cardiac "scintigraphy", which measures coronary perfusion, or the amount of blood flowing to the heart. Each patient was then followed for at least one year. Of the five patients, three showed marked improvements in blood flow to the parts of their hearts treated with the bone marrow-derived stem cells, and their chest pain also disappeared. The other two patients exhibited no change in blood flow when compared to preoperative tests, although no detrimental changes were found either. Chest X-rays, blood tests, electrocardiography and ultrasound studies were used to monitor the progress of each patient. Dr. Hamano and his colleagues are now treating a sixth patient as part of this continuing study. One of the most important findings, in addition to the regenerated tissue that was observed, is the increase in blood flow to the heart muscles that was generated by the stem cells.
As published in the June 7th, 2001 issue of the New England Journal of Medicine, scientists at the New York Medical College in Valhalla, New York, performed a "large-scale replication of heart muscle cells" in two regions of the human heart. One of the surprising results of this study is the implication of a naturally occurring cardiac stem cell. Piero Anversa, M.D., professor of medicine and Director of the Cardiovascular Research Institute at the NY Medical College, along with his colleagues, studied the myocytes (heart muscle cells) in thirteen patients who had experienced heart attacks and in ten patients who did not have cardiovascular disease. Myocyte samples were obtained 4 to 12 days after the heart attacks had occurred, from the "border zone" near the site of infarction and also from a site more distant from the damaged tissue. Myocyte replication was then observed using a high-resolution confocal microscope, with which Dr. Anversa and his colleagues were able to measure the expression of "Ki67", a protein found in the nucleus of dividing heart muscle cells, and which is expressed during all phases of a cell's life cycle and is a strong indicator of cell division. The formation of the "mitotic spindle" and "contractile ring" were also observed, both of which are critical structural indicators of cell division.
The mitotic index is also a measure of myocyte division and myocardial repair, and Dr. Anversa with his colleagues found that, in comparison with normal hearts, the number of myoctyes multiplying in diseased hearts as measured by the mitotic index was 70 times higher in the border zone and 24 times higher in the remote myocardium. The next step will be to discover the precise source of the dividing myoctyes. According to Dr. Anversa,
"There are preliminary indications that primitive cells like stem cells exist in the human heart. Are these cells a sub-population of known cells that retain the capacity to divide, or are they multiplying cells that originate from stem cells present in the heart? Stem cells have the ability to develop into the various cardiac cell types and form new healthy functioning myocardium. If we can prove the existence of cardiac stem cells and make these cells migrate to the region of tissue damage, we could conceivably improve the repair of damaged heart muscle and reduce heart failure."
The study was sponsored by a grant from the National Heart, Lung and Blood Institute (NHLBI), a division of the National Institutes of Health (NIH), and conducted in collaboration with scientists at the National Institute on Aging (NIA). According to Claude Lenfant, M.D., Director of the NHLBI,
"It has long been assumed that when the heart is damaged, such as after a heart attack, heart muscle cells do not regenerate and the damage is permanent. This assumption has been challenged in recent years by evidence that heart muscle cells may in fact regenerate. Now, this latest research provides the most dramatic and clear-cut demonstration to date of heart cell regeneration after cardiac injury. With this landmark study, we have a new understanding of the heart that opens up the possibility of repairing heart muscle damage after a heart attack."
David Finkelstein, Ph.D., Director of Basic Cardiovascular Research at the NIA, adds,
"This finding, if confirmed, may begin to clarify how hearts respond to the normal insults of aging through previously undetected repair mechanisms."
Dr. Anversa and a colleague at the National Institutes of Health had already reported in the April 4th, 2001 issue of Nature that adult stem cells which were isolated from mouse bone and injected into a damaged mouse heart transformed themselves into functioning heart muscle by developing into myocytes and coronary vessels. This new discovery, that the heart may actually contain its own "previously undetected repair mechanisms", offers the greatest hope yet in cardiac treatment. Although such a cardiac stem cell has not yet been precisely identified, scientists have found naturally occurring stem cells in other parts of the body, including a neural stem cell in the brain. Dr. Anversa therefore hypothesizes the existence of a naturally occurring cardiac stem cell, which could be stimulated and enhanced in conjunction with supplemental stem cell therapy.
Despite the revascularization that may successfully occur with treatment for heart disease, post AMI (acute myocardial infarction) deterioration still occurs and may lead to heart failure in some patients. The formation of scar tissue is associated with a decreased LVEF (left ventricular ejection fraction) which results in a pathological sequence of deterioration, such that the inhibited LVEF triggers dilation of the chambers of the heart, especially of the left chambers, ultimately leading to heart failure. Previous non-randomized studies had demonstrated that stem cells are capable of preserving heart function after such damage has occurred, and the first randomized, double-blinded, placebo controlled clinical trial was conducted on intracoronary autologous bone-marrow cell transfer after myocardial infarction, as reported by Wollert et al. in the journal Lancet in 2004. The corresponding video describes the conditions under which patients were admitted to the study and treated. (Please see the short video clip on heart disease in the "Videos" section of this website). Intervention included treatment with CD34+ stem cells derived from autologous bone marrow cells which were infused into the arterial area of infarction via the central lumen of a balloon catheter, which was transiently inflated inside the stent to interrupt antegrade blood flow, and infused during 4 to 5 coronary occlusions, each lasting between 2.5 to 4 minutes. Between occlusions, the coronary artery was reperfused for 3 minutes. The video indicates the medical characteristics of the patients, such that at 6-month intervals statistically significant increases in parameters such as LVEF were seen in the group that received the autologous bone marrow stem cells. Safety concerns were adequately addressed by a number of parameters. The autologous bone marrow stem cell therapy was found to induce statistically significant increases in global wall motion and in LVEF in the study, prompting other scientists to recommend combined modalities in future studies.
Similarly, the first multi-center, double blind, placebo controlled study of adult stem cells for post myocardial infarction heart failure was conducted by Schlichinger et al. and reported in the New England Journal of Medicine in 2006. After a heart attack, as mentioned, heart failure often still occurs, even with stenting, due to a series of cascading events which is triggered by scar tissue from damaged myocardium and which leads to decreased pumping action as indicated by a decreased left ventricular ejection fraction (LVEF), which in turn causes the heart to over-compensate by expanding the size of its chambers, ultimately culminating in heart failure. This study examined the ability of autologous bone marrow cells (BMC) to ameliorate post-infarct cardiac deterioration in a placebo controlled setting. Although a number of smaller studies had indicated that stem cells are able to inhibit this cascading series of events, no large-scale study examining such a claim had previously been conducted prior to this one, the purpose of which was to determine specifically whether or not autologous BMCs can ameliorate post-infarct cardiac deterioration in a placebo controlled setting. This study was one of the largest ever conducted on heart failure, with 103 participants in the control group and 101 in the group who received treatment. It was double-blinded, placebo controlled, randomized, and multi-centered, having been conducted at 17 hospitals, which included 16 in Germany and one in Switzerland. The corresponding video on heart failure under the "Videos" section of this website details the characteristics of the patients who participated in the study. Patients in both the control and treatment groups exhibited similar cardiac pathologies, and no one was found to have significant comorbidities, such as cancer. The stem cells were administered within 3 to 6 days after the successful reperfusion of the infarct-related artery, such that autologous bone marrow was extracted from the iliac crest of each patient and readministered via angiography to the infarct-related artery. At 4 months after the infusion, the patients who had been treated with the stem cells displayed a significantly increased LVEF when compared to patients in the control group who did not receive the treatment. At one year after infusion the group who received treatment showed a statistically significant reduction in the recurrence of myocardial infarction, and in the need for revascularization, and in death. Global safety was demonstrated by a number of parameters, thereby indicating both the efficacy and the safety of this procedure. Although this study was one of the largest ever conducted in the treatment of heart failure, over one of the longest periods of time, the researchers utilized relatively small amounts of autologous bone marrow, however, and other scientists now believe that such a treatment could be more efficacious if higher amounts of stem cells are used, and if the stem cells are derived from younger populations, such as those derived from umbilical cord blood, which should yield even better results and even stronger data.
Adult stem cells offer the same pluripotency of embryonic stem cells, but without the danger of forming teratomas (tumors), which remains a serious risk from embryonic stem cells. It is neither necessary nor desirable to use embryonic stem cells in the treatment of cardiac damage or other disorders, since a growing number of studies are showing increasing success with adult stem cells. In fact, the only stem cell studies that have ever shown success in the treatment of any human disease have involved adult stem cells, since no study has ever been conducted in which a disease was successfully treated with human embryonic stem cells, although this fact is not generally reported by the media. Ever since researchers first isolated human embryonic stem cells in 1998, there has never been a successful treatment for any human disease in a human being by embryonic stem cells. Embryonic stem cells have in fact proven to be very problematic, whereas stem cells from bone marrow, by contrast, have been safely used by doctors for over 40 years, and umbilical cord blood has been safely and effectively used in the clinical treatment of patients for over 60 years. Human umbilical cord blood in particular is now known to be a rich source of growth factors and cytokines, both of which are necessary for the regeneration of tissue, and stem cells that are derived from human umbilical cord blood have been shown to be more effective at tissue regeneration than are other types of stem cells that lack such additional factors. Ethics and politics aside, adult stem cells are highly preferable to embryonic stem cells purely for scientific reasons.