Saturday, July 28, 2012

Medical Megatrends – Stem Cells – Part II of III

Imagine a man with a recent severe heart attack who has the muscle repaired with stem cells or a child with a severe bladder defect repaired with stem cells grown on a biodegradable scaffold. Sounds like science fiction but these are actual clinical studies in progress today.
Stem cell therapies promise to be one of those scientific breakthroughs that will have an enormous impact on health care in the future. Stem cells will bring us closer to the goal of personalized medicine, just as genomics is doing. The course of a disease will change once we have the technology to develop and then insert stem cells into the human body to actually create a tissue. For example, a person with a heart attack will not go on to live the rest of his or her life with damaged heart muscle and resultant heart failure. Instead, stem cells will repopulate the heart muscle and make it whole again. Similarly, a person with Parkinson’s disease will recover full faculties thanks to the ability of stem cells to regenerate the damaged area of the brain. The person with type I diabetes will be free of the disease because of the formation of new pancreatic islet cells. The athlete will play again because new cartilage will be created for the worn knee. This is the promise of “regenerative medicine.” I have written the above as though each will definitely happen, a promise that will be kept. They probably will, but it may be a long time before the science of stem cells is sufficiently developed that these types of incredible results will be commonplace.
            Adult stem cells are being used today for treatment of a few diseases and there are studies ongoing and planned for many additional possibilities. Let’s consider a few of them. Each of our tissues has a population of cells that can divide as needed to keep the organ or tissue functional as cells die or are injured. We see this with our skin as it constantly lays down new cells which make their way to the surface as the dead cells on the surface are rubbed off in the shower. We also see it when we cut ourselves and yet in a few days the wound is completely healed – that was stem cells at work. It appears that essentially every organ has its own pool of such cells. There are cells in the bone marrow that can become stem cells for many different tissues. These cells circulate in the blood and can be called to assist a tissue or organ to rebuild itself after injury or damage. So for example, if a surgeon takes one half of a father’s liver for transplantation into his son, we know that the father’s liver will grow back to normal size within about 6 to 8 weeks. Some of the stem cells will have been those already in the liver but some will have come from the blood stream to assist. Of course, the liver is the exception to the rule that if a portion of an organ is removed by trauma or surgery, it will not grow back. Cut off your finger and stem cells will help it to heal but not to grow back to its original state. 
            Adult stem cells are the ones used for treating leukemia, myeloma and other cancers and for correcting certain childhood immune deficiencies. Most often is the use of allogeneic hematopoietic stem cell transplantation, meaning the use of stem cells obtained from a closely matched individual. An identical twin is ideal but few have such a potential donor. Only 25% of siblings will likely match completely. This leaves the use of the National Marrow Donor Registry to find as close a match as possible from unrelated individuals. The Registry has markedly improved the chances for a close match and thus for successful transplantation outcomes. Many parents are now having umbilical cord blood saved and frozen to have available in the unlikely event that their child requires a transplant many years later. Although these cells are identical they usually are not sufficient in numbers to lead to engraftment and often the white blood cells (neutrophils) recover only very slowly leaving a prolonged period of infection risk. Perhaps a technique will be found to get the umbilical stem cells to multiply in the laboratory so that a larger number would be available.
                        Adult stem cells are being used in studies of myocardial infarction and heart failure. Current guidelines of immediate angioplasty and stent insertion as appropriate help protect the heart from permanent damage after an infarct. Still, about 400,000 new cases of heart failure are developing in the USA each year. Long term survival is limited once overt failure develops. Could the damaged heart muscle be fixed? The concept is to use stem cells to repopulate the muscle fibers and to have those cells divide over and over and differentiate into new muscle fibers or perhaps also the small vessels that carry blood to the muscle cells.  So far there are some exciting animal studies and even some trials in patients that are encouraging enough to warrant further evaluations. For example, one study uses adult mesenchymal stem cells derived from the bone marrow and infused intravenously within 7 days after a heart attack. 42 centers are collaborating in this double blind, randomized trail in conjunction with Osiris Therapeutics. 220 patients will receive either the stem cells or a placebo and then be monitored with various imaging and functional studies.  So, stay tuned.
            Another common albeit less lethal problem is loss of bladder control leading to incontinence. There are studies in progress to determine if stem cells placed into the bladder’s sphincter muscle will help it regain control. The adult stem cells are obtained from a leg muscle biopsy. Stem cells are isolated and allowed to grow in tissue culture. These are then injected into the weakened bladder sphincter muscle. Once again, these are studies just beginning but with intriguing early results.
            Here is another bladder repair concept. When the bladder muscle is weak or largely missing in children it may be possible to literally rebuild the bladder by tissue engineering. A biopsy of the bladder yields cells that can be grown in the laboratory to large numbers. They can then be placed on a biodegradable scaffold and grown further. In time they seem to create a new bladder muscle wall complete with blood vessels. This layer of cells can be implanted in the bladder of children with a defect. Once more I need to note that it is still early days in these studies but they do raise exciting possibilities.
            The message here is that adult stem cells are being used today for life threatening and life impairing diseases with excellent success and are being studied in other diseases with exciting prospects for the future.

Saturday, July 21, 2012

Medical Megatrends – Stems Cells – Part I of III

             New cells to replace those destroyed in diabetes type 1, cells to help heal a heart attack, cells to cure leukemia – this is the promise of stem cells. Some of this is happening now; more will be available in a few years.
Stem cells will usher in the era of regenerative medicine, allowing the creation of cells, tissues and organs to treat or cure diseases and injuries. This will be a fundamental alteration in our approach to medical care and a transformational medical megatrend. And it will be very “personalized medicine” to provide the specific individual with custom tailored new cells and tissues for organ repair or replacement.
Extensive use of stem cells as therapy is still in its infancy. Call it infancy  because  there is so much basic science still to be understood, that it will be quite some years before we will see stem cells being used on any sort of regular basis to treat diabetes, Parkinson’s disease, or heart failure after a heart attack. But time flies, many investigators are hard at work and the science may advance quickly.
There are exceptions; stem cells are being actively used for a few situations and have been for many years. Among them are “bone marrow” or stem cell transplantation for diseases like leukemia, some cancers being treated with very high doses of chemotherapy or some individuals, especially children, with immune disorders.
            Since stem cells have the potential to be of ever increasing importance to medical care, albeit not for a few years, it is important to understand just what a stem cell is, generally how the various types of stem cells differ from each other and how they are either found in the body or produced in the laboratory. The key characteristics of stem cells are that 1) they can replicate themselves and 2) they can become mature cells that make up the tissue and organs of the body.
Embryonic stem cells are found in the earliest divisions of the fertilized ovum and can become any of the body’s approximately 200 types of cells (liver, lung, brain) and they have the capacity when placed in tissue culture in the laboratory to divide and to replicate themselves indefinitely. We call them pluripotent in that they can become any of the various types of cells in the body. Think of them as the most fundamental cellular building block that can create the tissues and organs of our body.
            Adult stem cells, as the name implies, can be found in the bodies of adults (or newborns and children for that matter.) They also can self replicate but when placed in tissue culture it has not been possible to have them replicate indefinitely as embryonic stem cells do. Adult stem cells generally only can differentiate into one type of the body’s cells or tissue, i.e., are unipotent. For example muscle stem cells only become muscle cells but not liver cells. But some adult stem cells, such as those from the bone marrow, can become multiple but not all types of cells. Stem cells obtained from the umbilical cord of a newborn baby are more like adult stem cells in that they can develop into some but apparently not all cells types. In effect, they are further along in the chain of differentiation.
There are also other types of stem cells that as of now are being produced in the laboratory and which have many of the attributes of embryonic stem cells – nuclear transfer, induced pluripotent, and protein-induced pluripotent stem cells, among others. To create the nuclear transfer stem cell, an unfertilized egg is obtained from a woman’s ovary. The egg has its nucleus extracted by a micropipette and then has the nucleus of an adult cell inserted in its place. This nucleus might be obtained from a skin cell taken from the arm of a patient with a particular problem such as diabetes. The newly created cell is placed in culture and with the appropriate signals begins to act like an embryonic stem cell in that it will divide and replicate itself and with the appropriate signals the daughter cells can become various body cell types. The hope is that these cells, genetically identical to the patient who had the skin biopsy, could be grown up into a vast number of – in this example – pancreatic islet cells and used to treat this individual patient’s diabetes. 
The induced pluripotent stem cell (or iPSC) also has many of the embryonic stem cells’ characteristics. It is produced by taking a person’s cells such as from the skin of the arm and then stimulating them by inserting a few key genes, using a retrovirus. These genes reprogram the cell to revert to what is similar to an embryonic stem cell. The concern of course is that it is induced using a virus. More recent experiments have found that certain proteins can reprogram the cell just as can the virally-inserted genes. These stem cells are known as protein-induced pluripotent stem cells (piPSC). Both are being evaluated to determine if they can be as effective as embryonic stem cells. With each of these three techniques, a clear hoped for advantage is that a person can donate his or her own cells for transformation into stem cells and from there into whatever cell is of interest, such as pancreatic islet cells that secrete insulin. Such cells transplanted back into the person would be recognized as “self” and not trigger rejection with a graft vs. host response by the body. This concept with each technique is therefore all about “personalized medicine.” 

Next time I will delve more deeply into adult stem cells followed the next time by embryonic stem cells. But in the meanwhile think of stem cell science as one more of those truly transformative medical megatrends that will revolutionize the practice of medicine in the years to come and in the process improve the healthcare of you and your family.

Wednesday, July 4, 2012

Antibiotic Resistant Bacteria Are A Major Threat – Preventing Transmission is Critical

Imagine a person that develops an acute problem that requires hospitalization and even a time in the ICU. Serious but something that modern medical care can deal with and cure. Until …the patient now develops an unexpected serious infection and despite excellent and appropriate medical care, dies. Unfortunately this scenario is all too common in today’s hospitals. 

More than 100,000 Americans die each year from hospital acquired infections; that is the infection developed only after admission to the hospital.  Many more develop and yet the patient survives.  The cost to the healthcare system is immense – $6 to 7 billion per year!  Many are caused by bacteria that are resistant to our most important antibiotics.  So prevention is critical.   

The antibiotic resistant bacteria are not new news but we often don’t appreciate how serious the problem really can be.  The use of new antibiotics, especially very broad spectrum antibiotics, creates the setting for a resistant bacteria to multiply and a healthcare setting like a hospital or a long term care facility (LTCF) creates the chance for patient to patient transmission.

Some bacteria like “staph” (Staphylococcus aureus) have become resistant to the most effective agents, especially penicillin derivatives such as methicillin and hence the term we are familiar with called methicillin resistant Staphylococcus aureus or MRSA.  At least one drug, vancomycin, is usually still effective although it must be administered intravenously.   

Another problem is what’s known as “carbapenem-resistant Klebsiella pneumoniae” (CRKP).  These bacteria have become rather frequent causes of serious hospital acquired infections.  Carbapenems are very powerful antibiotics developed to treat gram negative bacteria like this one.  But resistance has developed and when it occurs the resistance is usually to essentially all antibiotics, not just the carbapenems. 

Without a means of therapy, the key is to prevent transmission and hence infection.  Hand washing and the use of antibacterial lotions are critical.  Approaches to reduce contact are important as well.  Extensive disinfection of rooms and equipment is a must.  And avoiding antibiotics unless truly necessary is essential.  There are other critical steps related to each of the common sites of infections – IV line infections, pneumonias, urinary tract infections, post-operative wound infections, etc. Adherence to check lists of evidence-based prevention protocols are key.  

The hands of providers are a major route of transmission. Hand washing and antibacterial lotions work but only if used. Hospitals need to enforce the rules and put sanctions that have meaningful teeth in place (such as exclusion fromr the OR or not able to admit patients for a week for the observed second offense -- both of which are economic sanctions that get the providers’ attention.) Isolation procedures with gloves, mask, gown and booties are needed in some situations to prevent transmission from room to room, patient to patient.  

Even extensive attempts at disinfecting the patients rooms (or ICU cubicle, OR or procedure room) may not be adequate, leaving viable organisms behind. Newer approaches such as room misting with binary ionization of low strength hydrogen peroxide (StereaMist) when used according to protocol can effectively destroy all bacteria, fungi and viruses plus spores such as C difficle. The process is fast (less than ten minutes per room), the material kills on contact, converts to oxygen and water, and the room is immediately ready for the next patient. SteraMist is relatively new so this is not an endorsement but it may be worth considering for further due diligence. (Disclosure – I have gotten to know the company, Tomi Environmental Solutions, through some consulting) 

Many hospitals now have antibiotic “stewardship” programs designed to assure that broad spectrum antibiotics are used only when absolutely indicated, are discontinued as soon as possible, and are converted to narrower spectrum agents once the causative bacteria is defined. These programs are effective at reducing the use of these agents, thereby reducing the opportunity for resistant organisms to spread and infect patients and have the side benefit of reducing costs quite substantially. 

One major issue, often not appreciated, is that patients arrive at the hospital already colonized with resistant bacteria.  Residents of long term care facilities (LYCF) are often colonized in part because the individuals may have picked up the bacteria during a recent hospitalization.  And spread from person to person in the LTCF setting is relatively commonplace – what with multiple occupancy rooms and common dining and activity areas.  Some LTCF residents often have multiple medical conditions and so they are more susceptible than others to having an infection develop, sending them back to the hospital.  A sort of vicious cycle is compounded by various underlying chronic illnesses that render the resident more susceptible to infection. 

Hospital acquired infections cause many deaths and much suffering in addition to substantially adding to the costs of care. The rise of antibiotic resistant bacteria has now reached critical importance.  With few or no antibiotics available now nor on the horizon to treat infected patients, preventing transmission is absolutely essential.  This is a lot easier said than done but it can be done and there is no excuse for not doing so. 

Post Script: My new book, The Future of Healthcare Delivery – Why It Must Change and How It Will Affect You, has a chapter that discusses this issue in more detail.  See for more information. 

Praise for Dr Schimpff

The craft of science writing requires skills that are arguably the most underestimated and misunderstood in the media world. Dumbing down all too often gets mistaken for clarity. Showmanship frequently masks a poor presentation of scientific issues. Factoids are paraded in lieu of ideas. Answers are marketed at the expense of searching questions. By contrast, Steve Schimpff provides a fine combination of enlightenment and reading satisfaction. As a medical scientist he brings his readers encyclopedic knowledge of his subject. As a teacher and as a medical ambassador to other disciplines he's learned how to explain medical breakthroughs without unnecessary jargon. As an advisor to policymakers he's acquired the knack of cutting directly to the practical effects, showing how advances in medical science affect the big lifestyle and economic questions that concern us all. But Schimpff's greatest strength as a writer is that he's a physician through and through, caring above all for the person. His engaging conversational style, insights and fascinating treasury of cutting-edge information leave both lay readers and medical professionals turning his pages. In his hands the impact of new medical technologies and discoveries becomes an engrossing story about what lies ahead for us in the 21st century: as healthy people, as patients of all ages, as children, as parents, as taxpayers, as both consumers and providers of health services. There can be few greater stories than the adventure of what awaits our minds, bodies, budgets, lifespans and societies as new technologies change our world. Schimpff tells it with passion, vision, sweep, intelligence and an urgency that none of us can ignore.

-- N.J. Slabbert, science writer, co-author of Innovation, The Key to Prosperity: Technology & America's Role in the 21st Century Global Economy (with Aris Melissaratos, director of technology enterprise at the John Hopkins University).