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.

Genomics – a Revolution in Medicine – Part 2

In the previous post I discussed the field of pharmacogenomics. Today I will focus on


Disease classification
Disease prognostication
Early and rapid diagnosis
Prediction of diseases to develop later in life

Genomics is proving to be very valuable in disease classification, especially with cancer. A pathologist’s evaluation looking at a microscopic slide has been the basis for most cancer classification - separating out breast cancer from lung cancer but then sub classifying each such as small cell and non-small cell lung cancer or the various subcategories of lymphomas. To this was added some years ago histochemical analysis to learn if a breast cancer was high in estrogen or progesterone receptors and then molecular diagnosis to find, for example, if the tumor had a high complement of the receptor Her2neu – each being important markers for the approach to treatment. Now genomics is adding an ability to delve much more deeply and find what the DNA mutations are in the individual tumor and how they are similar or different from others. This in turn is leading to searches for new drugs, as discussed last time.

This same work allows for early prognostication. Consider 100 women with breast cancer that appear by all the usual criteria to be the same type and of the same early stage. We know that most of them will respond well to current therapy of surgery, radiation locally and, in certain circumstances, systemic chemotherapy or hormonal therapy. But a small percentage will have a relapse. The problem is that there has been no way to determine in advance who is at risk of relapse. Genomics has begun to answer this problem. Analyzing the genomics of the tumor at the time of diagnosis, it is possible to separate these women into a good prognosis group and a poor prognosis group. The former rarely relapse and one might even consider if they need the same level of aggressive therapy as they are now getting. And the latter group is at high risk of recurrence; they are obvious candidates for clinical trials of alternate approaches to determine if relapses can be reduced. One such genomic prognostic test has been approved by the FDA and others are in the works for multiple cancers.

Genomics can be used for early diagnosis, especially in the field of infectious diseases. Remember the gentleman who flew to Italy on his honeymoon but who had tuberculosis? It led to an international concern that he might have infected others and that his TB might be of the drug resistant variety. One of the problems was that it takes about six weeks to grow the TB bacteria in the laboratory and then, if present, another six weeks to test for antibiotic susceptibility. But genomic tests can speed that process up to just hours. The TB bacteria (Mycobacterium tuberculosis) has a characteristic genomic profile so, if present in a sample from the patient, it can be detected within hours. And since antibiotic susceptibly is driven by the bacteria’s genes, they can be analyzed at the same time. A huge improvement in time to diagnosis and getting the right drug started from the beginning.
We might want to know if we are predisposed to develop a certain disease later in life. It is possible that genomics can be of real assistance here; indeed this has been a major “promise.” It turns out that most of the common, important diseases such as diabetes and coronary artery disease have not one but vast numbers of genes that have some impact on their development. So we will not find a simple answer for many of these. But as more is learned it is very possible that each of us will be able to learn our relative risk to some important and common illnesses. If you knew, for example, that you were at increased risk of heart disease, it might be a stimulus to you to be more diligent in eating a Mediterranean style diet, exercising more often and looking for ways to control stress- and it would be an added inducement to stop smoking. Similarly, if you were at risk for early onset colon cancer, you might be more careful to eat a diet high in fiber and low in fat and begin having colonoscopies at an earlier age.

These are just some of the advances coming from genomics; expect to see many more because genomics represents a true revolution in medicine and we have only seen the beginning.

Here is a video on medical megatrends

Misconception - Healthcare reform will have an impact on the advances in medical science.

This sounds logical but there are frankly amazing advances in medicine that are around the corner no matter what “reform” occurs. These advances are related to our national commitment to basic science and to engineering and computer science developments and their translation to clinical care. The National Institutes of Health, research organizations such as our medical schools, the pharmaceutical and biotechnology industries and the medical device industry are constantly bringing forth new knowledge and new approaches to care. Among them are advances in genomics, stem cells, transplantation, vaccines, pharmaceuticals, medical devices, imaging modalities, OR technologies and the digital or electronic medical record. [For more of this subject see “The Future of Medicine – Megatrends in Healthcare.”] The reforms being discussed will have little or no impact on the development of these advances; rather they are coming and they will have a major impact on the care we will receive in the near future.

Additional Advances To Expect in Medical Care

In the last post I referred to the advances in biological sciences and some in engineering and computer science. Here are some more that will have a tremendous impact on your care now and into the future.

With the improvements in imaging devices such as MRI and CT scanners, it is now possible to do many procedures much less invasively in the radiology suite rather than in the OR as before. Uterine fibroids can be destroyed by passing a small catheter [about the size of a spaghetti noodle] into the arteries that feed the fibroid. Then small particles are inserted that block off that blood supply and the fibroid basically withers away. It is a rapid procedure with minimal recuperation time, especially compared to surgical removal of the uterus [hysterectomy.] Another example is resolving an aneurysm in the brain using similar catheters without the need for open neurosurgery.
Some tumors of the brain can be successfully treated with the “gamma knife” which is designed to give a huge dose of radiation to the tumor but not the rest of the brain. It is done in one procedure and the patient goes home the same or the next day. Other new radiation therapy procedures utilize very sophisticated equipment that can deliver the correct dose of radiation to the tumor, say in the prostate, but avoid most of the surrounding tissue such as the rectum and bladder. This makes the treatment more effective yet with fewer side effects.

Slowly but surely, all medical information is being digitized. As this happens it will be finally possible to have a total electronic medical record. This will mean your medical data is available anyplace, anytime. And it will mean that if you are sent to a specialist that your CT scan is available on line and you will not have to go to the radiology office to get it before visiting the specialist. This will save you time; the specialist can make an informed opinion immediately and will mean reduced costs. There are some important hurdles to overcome before this will be a reality but I am confident that they will be solved relatively soon.

With these and other advances medical care will be more custom tailored just for you; there will be a greater focus on prevention; it will be possible to repair, restore or replace a damaged organ; your medical data will be instantly available and medical care will be safer. Big advances.