Worldwide, about 23 million people have heart attacks each year. Half of them die within five years. In the United States alone, heart failure costs $40 billion a year.
Mending a Broken Heart with Stem Cells
Worldwide, about 23 million people have heart attacks each year. Half of them die within five years. In the United States alone, heart failure costs $40 billion a year.
While we’ve made a lot of progress in preventing heart attacks over the past 50 years, there has been no way to undo the damage a heart attack leaves behind in survivors. Fortunately that’s all changing.
The field of adult stem cell research and therapy is exploding right now, and its advances promise to change the way medicine is practiced and to improve the lives of millions ? not just heart patients but people with a wide range of diseases.
Stem cells are the precursors of all the tissues in the body. In theory, a stem cell could grow and change to become anything from nerve tissue to heart muscle to skin or bone or blood. In fact, all our tissues start out as stem cells. Although this has been known in theory for a long time, until fairly recently no one was sure if it could be useful in replacing or repairing damaged tissues in living bodies.
First let’s review the relevant history:
Scientists in the early 1900s noticed that a simple cell in bone marrow would transform itself into a more complex one, producing blood cells. They called these stem cells. In fact, a bone marrow transplant ? used to treat leukemia, among other diseases ? is simply a transplant of stem cells.
Physicians have long suspected that stem cells might have curative properties. A century ago they were giving leukemia patients bone marrow by mouth. Although it had no effect, their thinking eventually led them to inject bone marrow into the bloodstream of mice, which did have therapeutic effects. The first successful human treatments that might be termed “stem cell therapy” were bone marrow transplants conducted in France in the late 1950s.
By 1958, a French researcher discovered human histocompatibility antigens, known as HLA antigens. Those are the proteins on the outside of a cell that are responsible for the immune response that causes rejection, and their discovery led to great strides in stem cell research. For one thing, scientists came to understand that for bone marrow transplants or any other stem cell therapy to work, the HLA antigens had to be compatible. This led to continuing improvements through the sixties, and by 1973, the first unrelated bone marrow donors were being used successfully in transplants. This set the stage for all the stem cell research to come.
By the late 1990s, researchers were able to grow stem cells in the lab and had begun to see unexpected results in experiments with mice. When they injected bone marrow stem cells, for example, they saw them turn into nerve tissue or liver cells. They found that stem cells found in the brain could turn into other tissues as well. Stem cell research began to accelerate as researchers raced to publish a long list of firsts.
It was only in 2000, that scientists at New York Medical College first demonstrated that bone marrow stem cells could regenerate heart muscle in mice. The mice, which had severely damaged hearts, grew new muscle tissue and blood vessels. Their lives returned to normal.
Suddenly, the race was on. Within months, German doctors at Dusseldorf, Frankfurt, and Hanover had begun clinical trials on human heart patients. Other human trials followed in rapid succession in China, Korea, Brazil, and only in the past year or so, in the U.S. They’re taking place now at Saint Elizabeth’s Medical Center in Boston, at the Texas Heart Institute, and at Columbia University in New York. Another trial will soon begin at Johns Hopkins.
Needless to say, there is great excitement in the pharmaceutical and biomedical industries as the pace of developments accelerates. With billions at stake, those companies able to take advantage of this paradigm shift in therapeutics ? not only for heart disease but for other diseases as well ? will reap huge rewards. And many firms already have a place at the table, according to an article in the November 15, 2004 issue of Fortune.1
In the Boston trials, for example, patients must first receive treatment to stimulate bone marrow growth with a drug called Neupogen, made by Amgen. Baxter, Cordis, and Boston Scientific are all pitching in to help sponsor the trials and stay close to the action.
Smaller firms are developing niche products. Miltenyi Biotech in Germany makes devices to isolate stem cells. Gamida-Cell in Jerusalem specializes in promoting growth of stem cells outside the body for eventual implantation in the heart. Anormed in Vancouver is developing a drug to compete with Neupogen, which causes stem cells to move from the bone marrow to the bloodstream, where they’re easier to harvest.
Two competing firms, Osiris Therapeutics in Baltimore and Angioblast Systems in New York, are racing to dominate the field of mesenchymal stem cells, an especially versatile type of cell that promises to be used for dozens of diseases.
And San Diego-based MacroPore Biosurgery is commercializing a heart repair process using stem cells derived from the patient’s own fat tissue, which regenerate hearts even faster than bone marrow cells, according to an article in the September 26, 2004 issue of the Deseret Morning News.2
Bioheart, Inc. has developed stem cells from adult muscle tissue and a technology for delivering them to ailing hearts. Its first- and second-stage clinical trials were reported in January to the meeting of the American Heart Association, according to the journal Heart Disease Weekly3 in its January 23, 2005 issue.
In fact, new sources of stem cells are being discovered all the time. As reported in the January 2004 issue of the journal Developmental Dynamics,4 they were recently found in hair follicles at the Medical College of Wisconsin. These cells, which can be taken from the patient’s own skin, have been turned into nerve cells, cartilage, bone, muscle, skin pigment, and other tissues in mice.
Meanwhile, scientists at Johns Hopkins School of Medicine are using stem cells to create biological pacemakers that could replace the mechanical ones, according to the December 20, 2004 issue of the journal Circulation.5 In another test, researchers there restored control of limbs in paralyzed rats by injecting stem cells into their spinal fluid.
Stories of amazing recoveries are emanating from the clinical trials. People who couldn’t walk across the room before are hiking in the Rockies. People’s lives and happiness are restored. More than 400 people have now received adult stem cells for heart disease, according to the January 1, 2005 issue of the Harvard Heart Letter,6 and pressure is mounting on the FDA from patients, doctors, and biomedical companies to start approving these therapies for the general public.
This may be the first widespread use of stem call therapy. Meanwhile, waiting in the wings are similar treatments for diabetes, Parkinson’s disease, spinal cord injuries, Alzheimer’s, Lou Gehrig’s Disease, and a host of others.
In a truly striking breakthrough, researchers at Johns Hopkins recently found that the heart itself has its own reservoir of stem cells, ready to be harvested and turned back into healthy muscle and new blood vessels.7 In experiments with mice, these cells have proved better at repairing the heart than bone marrow cells, according to the presentations at last November’s meeting of the American Heart Association. Human trials for this therapy should be underway in about a year.
What are the implications for all these astounding research developments? Based on the convergence and acceleration of these trends, we offer the following six forecasts for your consideration:
First, the world-wide competitive frenzy to dominate these new fields ? in both research and medical applications ?will only intensify between now and 2015. Research scientists will be competing to advance their careers and reputations. Physicians will be competing to become the Michael Debakeys or Christian Barnards of this therapeutic field. And both will be partnering with pharmaceutical and biomedical firms, which will be competing to control the accepted standard of care in stem cell treatment for cardiac and other diseases.
Second, in this atmosphere of fast-paced, winner-take-all competition, there will be a number of big shakeouts as the therapies become commercially mainstream between 2010 and 2015. A few pharmaceutical and biotech giants will gobble up the most promising smaller companies to take advantage of their breakthroughs. Academic institutions will try to lure the best scientists to their labs. And even specialized physicians may find themselves joining forces with each other to stake out the new territory. Stem cell clinics are likely to become big business. Similarly, those whose careers are linked to older therapies will be forced to adapt or be marginalized.
Third, the debate over embryonic stem cells is likely to become moot. With all the different types of adult stem cells and new sources of them being discovered almost every month, it simply won’t be necessary to develop most of the therapies researchers might imagine. That “tempest in a teapot” is expected to quietly fade from the editorial pages within two to five years.
Fourth, a new debate will arise about which of the myriad types of adult stem cells is the best one to use. This may divide institutions, doctors, and even companies into competing camps, with one touting bone marrow while another tries to sell the patient his own hair follicles. Following what is bound to be a cascade of FDA approvals, we will not be surprised to see companies advertising their take on stem cell therapy the same way prescription drugs are sold directly to consumers on television and in magazine ads.
Fifth, over the next 20 years, heart patients will lead far more active, normal, and productive lives than they do today. Heart transplants may well become a relic of medical history. The widespread commercial success of stem cell therapies for the heart will pave the way for their use in treating diseases like Parkinson’s and Alzheimer’s. For that reason, those diagnoses will no longer be seen as death sentences and those who suffer from them will enjoy a much better quality of life. Similarly, cases of spinal cord injury that now result in life-long paralysis will be treatable, with total function restored in many cases that previously would have been hopeless. And countless other diseases will also be rendered relics of the past.
Sixth, the economic and quality of life benefits will accrue, not just to the health care providers and the patients, but to society in general. One of the biggest costs to Medicare is taking care of older people with heart problems. Furthermore, many older people are no longer economically productive, not because they don’t want to work, but because they are disabled by heart problems. Though difficult to quantify at this point, the reduced cost burden on the system, coupled with a substantial increase in production and consumption by healthier and happier seniors, can be expected to substantially energize the economy during the otherwise weak decade beginning in 2010.
References List : 1. Fortune, November 29, 2004, “Stem Cells to Fix the Heart,” by David Stipp. ⓒ Copyright 2004 by Time Warner, Inc. All rights reserved.2. Deseret Morning News, September 26, 2004, “Adult Stem Cells Aid in Heart Repair,” by Michael Fumento. ⓒ Copyright 2004 by Deseret News Publishing Co. All rights reserved.3. Heart Disease Weekly, January 23, 2005, “Heart Failure: Trial Data on Stem Cell Treatment of Heart Failure Presented.” ⓒ Copyright 2005 by Newsrx. All rights reserved.4. Developmental Dynamics, October 2004, Vol. 231, Issue 2, “Pluripotent Neural Crest Stem Cells in the Adult Hair Follicle,” by M. Sieber-Blum, M. Grim, Y.F. Hu, and V. Szeder. ⓒ Copyright 2004 by John Wiley & Sons, Inc. All rights reserved.5. Circulation, January 4, 2005, “Functional Integration of Electrically Active Cardiac Derivatives from Genetically Engineered Human Embryonic Stem Cells with Quiescent Recipient Ventricular Cardiomyocytes,” by Tian Xue, Ph.D., Hee Cheol Cho, Ph.D., Fadi G. Akar, Ph.D., Suk-Ying Tsang, Ph.D., Steven P. Jones, Ph.D., Eduardo Marban M.D., Ph.D., Gordon F. Tomaselli, M.D., and Ronald A. Li, Ph.D. ⓒ Copyright 2005 by the American Heart Association, Inc. All rights reserved.6. Harvard Heart Letter, January 2005, “Damaged Heart? Grow Around It!” ⓒ Copyright 2005 by President and Fellows of Harvard College. All rights reserved.7. Circulation, December 21, 2004, “Both Cell Fusion and Transdifferentiation Account for the Transformation of Human Peripheral Blood CD34-Positive Cells into Cardiomyocytes in Vivo,” by Sui Zhang, M.D., Ph.D., Dachun Wang, M.D., Zeev Estrov, M.D., Sean Raj, James T. Willerson, M.D. Edward T.H. Yeh, M.D. ⓒ Copyright 2004 by the American Heart Association, Inc. All rights reserved.
