Autologous Bone Marrow Cells Improve Chronic Heart Failure

Stem cell research has been in the news a great deal over the past two years.  Most of the controversy regarding this field is related to the use of fetal stem cells, which must necessarily be harvested from human embryos.  However, researchers in several countries have recently discovered that our bodies continue to produce so-called pluripotent stem cells well into adulthood.  These cells, under the proper conditions, are able to differentiate into almost any type of cell that the body might require.  Theoretically, such stem cells can form the differentiated cells that make up muscle, nerves, blood vessels, kidneys, pancreases, and virtually any other tissue or organ of the body.  The issue of fetal stem cells is not altogether moot, however.  Research has shown that fetal stem cells possess a much greater potential to form differentiated cells when compared with stem cells taken from adults.  Moreover, as we age, our bodies produce fewer and fewer stem cells, making it difficult to harvest large numbers of these progenitor cells from adult individuals.

In the current issue of the journal Circulation is a fascinating study that looked at the use of autologous (taken from one’s own body) bone marrow stem cells to treat chronic heart failure induced by coronary artery disease.  The study evaluated 21 patients with end-stage ischemic heart disease.  The first 14 people in the study underwent injections of their own bone marrow stem cells into the lining of their hearts, while 7 additional patients served as controls, and received injection of saltwater, only.  When compared with the control patients two months after the injections, there was a significant reduction in the size of heart muscle lacking adequate blood supply, and an improvement in the heart’s ability to pump blood, in the patients that had received their own stem cells.  At 4 months, the patients who had received their own stem cells experienced, on average, a 31% increase in the ability of the heart’s main chamber, the left ventricle, to pump blood to the body.  Electromechanical studies of the patients’ hearts revealed significant improvement in the ability of the injected portions of their hearts to pump blood 4 months after injection.

This study reveals a possible role for autologous stem cell injections into ailing heart muscle as a means of safely improving heart function.  The patients included in this study had end-stage heart disease that was not amenable to surgical or non-surgical correction and, thus, represented an enormous therapeutic challenge.  The advantages of using a patient’s own bone marrow stem cells include the alleviation of any concerns about the ethics of fetal tissue culturing, or about the potential for rejection of transplanted tissue from another person.  The next logical step in this type of research is to assess larger numbers of patients after injection of their autologous stem cells, and to determine if the improvements in cardiac function noted in this study actually translate into clinically significant improvements in the health of injected patients.  Longer term follow-up is also necessary to determine how durable these favorable changes in cardiac function are following stem cell injections.  This is, however, a fascinating and provocative study, and opens the door to potentially practical uses for autologous stem cell autotransplantion.

Reversal of Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that occurs primarily in women of child-bearing age.  The disease arises due to the development of antibodies against a patient’s own DNA.  The most common manifestations of SLE include a “butterfly” rash of the cheeks and nose, kidney failure, arthritis, blood clots; as well as inflammation of the heart, brain and lungs, and anemia.  The usual treatments for active SLE include steroids and other immunosuppressive medications.  Unfortunately, these drugs are associated with serious and sometimes life-threatening complications.  More recently, some researchers have tried using monoclonal antibodies that block a type of immune cell referred to as CD4+ helper T-cells.  The autoimmune response that occurs in SLE patients is largely due to the hyperactivation of these CD4+ helper T-cells.  These are the same cells that are depleted by the HIV virus, resulting in severe immune system failure.  Treating SLE patients with antibodies that knock-out these same CD4+ cells has, not surprisingly, resulted in severe immunodeficiency syndromes not unlike AIDS.

In the current issue of the Journal of Clinical Investigation, researchers used an antibody against a protein called CD137, which stimulates CD4+ cell immune function.  This study used mice with a form of SLE that closely mimics the SLE that is seen in humans.  The CD137 antibody blocks the function of the CD137 stimulatory protein, thus decreasing the ability of CD4+ helper T-cells to cause autoimmune injury to the vital organs of mice with SLE.  After three injections of the CD137 antibody, the signs and symptoms of SLE were reversed in the SLE-afflicted mice, and their lifespan was increased to an average of 2 years (as compared to the 10 month lifespan observed in the untreated mice with SLE).  At the same time, the CD137 blocking antibody did not cause the same sort of severe immunodeficiency that antibodies directed against CD4+ helper T-cells have been known to cause.  The authors concluded that blocking the CD137 protein renders CD4+ helper T-cells unable to attack the body’s own DNA, but does not prevent the these lymphocyte cells from performing their normal immunologic functions.  This discovery may hold significant hope for patients with SLE.

More News on Physical Inactivity & Cancer Risks

I have recently discussed research linking low levels of physical activity with an increased risk of developing certain cancers.  In the current issue of the journal Cancer are two new research reports relating to this same topic.  The first study looked at the correlation between physical inactivity, diet, obesity and the risk of rectal cancer in Canada.  The study evaluated 1,447 patients with rectal cancer and 3,106 control patients without a history of rectal cancer between 1994 and 1997.  The authors of the study considered total recreational physical activity, caloric intake and obesity as potential risk factors for rectal cancer.  They determined that patients reporting the highest levels of exercise experienced a 19% reduction in the risk of rectal cancer when compared with patients reporting the lowest amount of regular physical activity.  The group of patients reporting the highest levels of caloric intake experienced a 50% increase in the risk of developing rectal cancer when compared to people reporting more restricted caloric intakes.  Unlike other studies, however, dietary fat content did not appear to be a significant risk factor for rectal cancer in this study.  Obesity, as defined by a body mass index (BMI) greater than 30, conferred a 40% increase in the risk of rectal cancer in women and a 78% increased risk for men when compared to people with normal BMIs.  The greatest cumulative risk for developing rectal cancer was observed in men and women with simultaneous high caloric intakes, high BMI, and low levels of recreational physical activity.  These findings suggest that these three factors additively increase the risk of developing rectal cancer.  More importantly, all three of these risk factors can be essentially eliminated by almost all of us.

The second related study in the journal Cancer looked at the risk of developing ovarian cancer as a function of physical activity levels.  This study was performed in China, from 1999 to 2000, and looked at 254 patients with a history of ovarian cancer, as well as 652 control patients without a history of ovarian cancer.  A detailed questionnaire was completed by each study participant.  In general, women who engaged in high levels of physical activity throughout the week experienced a 46% reduction in the risk of developing ovarian cancer.  Among premenopausal women, prolonged durations of strenuous sports activity reduced the risk of developing ovarian cancer by a whopping 87%.  Frequent sweat-inducing activity throughout the week reduced the ovarian cancer risk in premenopausal women by 55%.  Among postmenopausal women, prolonged durations of even moderate physical activity resulted in a 64% reduction in the risk of developing cancer of the ovaries.

The accuracy of these types of case-control studies depends heavily upon the quality of the questionnaires used by study volunteers, and by the ability of the researchers conducting such studies to adjust for other factors that might skew the resulting data.  However, both of these studies are consistent with previous studies that associate sedentary lifestyles, and excessive food intake and body weight, with an increased risk of multiple illnesses, including cardiovascular disease, high blood pressure, diabetes, stroke and cancer.  As I have already stated, all of these risk factors are modifiable for the vast majority of people in our society.  In our rush-rush fast-food society, it may be difficult to increase one’s duration and frequency of exercise, to cut back on calories, and to lose weight.  But the costs of ignoring these excesses can be very high indeed.

Internet & E-mail Use for Health Care Purposes

Quite naturally, I was intrigued by the results of a survey that was published in the current issue of the Journal of the American Medical Association (JAMA).  Like most physicians, I have experienced the increasingly common phenomenon of patients coming into my office with a stack of papers that they have culled from the Internet.  As a cancer surgeon, I have found that I need to remain very sharp about current developments and controversies in cancer medicine.  This is not only the case so that I can provide the best possible care to my patients, but also because many of my patients are exhaustively mining the Internet for every available update about their illnesses.  Like other denizens of our current Information Age, I have had to modify my behavior to conform to current realities.  However, I know many physicians who still shudder when patients come into their offices with piles of print-outs from the Web.  A few of my colleagues admit to frankly resenting this perceived challenge to their authority and expertise as well.

The survey published in JAMA polled 4,764 adults who were self-reported Internet users.  Approximately 40% of the survey participants with Internet access reported using the Web to seek advice or information regarding health care issues in 2001.  A smaller number, 6%, used the Internet to send E-mail inquiries directly to a physician.  Among the 40% who used the Internet to research health care issues, about one-third reported that the information they had gleaned from the Net affected a decision regarding their health or health care issues.  However, 94% of the people who used the Internet for health or health care research stated that their Internet usage had no impact on the number of visits they made to physicians.  Less than 5% of the Internet users reported that they obtained or paid for prescription medications via the Internet.

The survey’s authors concluded that many people do use the Internet for health-related concerns, although the actual numbers are probably much lower than previous estimates.  The impact of Internet usage for health and health care concerns also appears to have very little impact on the actual utilization of health care resources, which is also contrary to the perception of some experts on the subject.

I find this study’s conclusions rather interesting, as my own experience has been quite different.  There is clearly some selection bias in my case, in that new patients who come to see me are often seeking second or third opinions for complex disease processes, and are presenting at a tertiary cancer treatment center with an international reputation.  In any case, many of the patients that I see, both old and new, closely follow new treatment developments reported via the Internet.  They are not shy about putting me on the spot, nor do they blandly accept my opinions without running at least some of them through their Internet chat groups.  It’s a new age that we live in, and all of us, physicians included, must adapt or be left behind.

Dr. Robert A. Wascher