The above diagram shows the difference between normal bone and osteoporotic bone. We can see that the osteoporotic bone has much bigger holes and in general is much weaker bone. When we talk about Osteoporosis I can wear both of my hats. The hat of an orthopedic surgeon and that of a Regenerative Medicine stem cell doctor. For 35 years I have seen first hand the ravages of osteoporosis. I have operated on thousands of fractures that were caused by osteoporosis. Many of these fractures were quite challenging. The fixation of the fractures required different surgical solutions including plates, rods, and screws and different combinations. These fractures were the precursor of many other serious problems such as blood clots, strokes, pneumonia and other serious medical problems. The next slide shows the incidence of osteoporosis in the USA.
There is not any widely accepted treatment for osteoporosis. In the above diagram we can see some of the methods that are used to treat osteoporosis. Unfortunately, these treatments are at best band aid approaches. Last year a meta-analysis of no fewer than 33 studies was published in the prestigious BMJ (the former British Medical Journal). This study confirms what had been suspected. Namely, that bisphosphonates are totally ineffective at preventing fractures.
Bisphosphonates are a class of osteoporosis drugs such as Boniva (ibandronate), Fosamax (alendronate), Actonel (risedronate) and Reclast (zoledronic acid). Their mode of action is to disrupt normal bone remodeling, which is ultimately detrimental to bone integrity and fracture resistance. They do not increase bone density but slow down bone loss. Teriparatide also called Forteo is the only osteoporosis medicine which has been shown to have the potential to rebuild bone. It has to be given as a daily injection and one of its risks is that it can cause a bone cancer called osteosarcoma. As can be seen none of these medicines are a bargain. Either they do not work or have a significant risk.
The interesting new aspect concerning Osteoporosis is the use of stem cells to treat osteoporosis. The following slides give a good idea of what the stem cells are
doing.
From this slide we get a better idea of the concept of how stem cells can treat osteoporosis. The cell we are talking about is not any stem cells but what we call an Adult Pluripotent Embryonic-Like Stem Cell. Also called a VSEL stem cell. These cells are revolutionary. We are fortunate in that we are one of the few facilities that are utilizing these cells. I describe these cells as an emergency stem cell supply. They are found in everyone but typically they are not activated. One of the common threads on the studies with these cells is that they seem to be activated by cold temperatures. The propriety information here includes the methods to dramatically increase the number of cells released, how to activate them and finally how to keep them going. We are fortunate to be able to utilize this technology. The technique is relatively non-invasive. It requires an
injection or two of some propriety compounds and then a harvesting of some blood. We have utilized these cells for a few years. They work exceptionally well with auto-immune diseases (a type of condition where the body can attack itself) such as Rheumatoid Arthritis and Ankylosing Spondylitis. We also use them for anti-aging as well as for musculoskeletal conditions with good success. When we talk about osteoporosis we think osteoporosis is somewhat like an autoimmune disease. We have seen some of our preliminary results with using these cells for osteoporosis. The results are astounding. The slide below shows one of the patients we have treated. We have had similar results in other patients we have
treated for osteoporosis. As can be seen this patient has received two injections of the pluripotent cells. They were spaced about one year apart. Our recommendations are to perform two of these treatments a year, spaced approximately 6 months apart. We are also placing the patients on some propriety growth factors and supplement mixes.
To make things somewhat easier I have included the patient's most recent bone density report below. I think that this is easier to follow.
This report shows the patient's bone density INCREASED 14% IN LESS THAN 6 MONTHS!! This increase is exceptional. There is currently no treatment for osteoporosis that I am aware of that would even approach this amount of improvement.
Unlike many things in regenerative medicine we see very specific improvement in results in a test (bone density) that is completely objective. The implications of this treatment are profound. If we are able to turn the tide of osteoporosis it will save our health care system billions of dollars. The amount of money spent on a fractured hip is astounding. More importantly this treatment can dramatically improve the quality of life of the patient. Fractures take a toll on the patient and their families. The problem with osteoporosis is that it is a silent problem. Most of the time you have osteoporosis or its less severe counterpart which is called osteopenia there are initially no symptoms. The symptoms occur when fractures start happening. Other manifestations include some wedging of the vertebral bodies (back bones) which can cause spinal deformities. As far as other manifestations of the VSELs we have seen significant improvements in the treatment of auto-immune diseases. We have had a number of patients go off their medications for these diseases. Some of the side effects for these medications include developing a lymphoma. There also seems to be some manifestations of some anti-aging properties but I will leave this for another blog. We are very high on these cells. I will be attending and lecturing at a meeting in Kuala Lumpur on Dec. 17 and 18. This meeting will present some of the newest information on VSELs by those experts in the world involved with these cells. Some of the topics will include infertility, treatment of various inflammatory diseases including COPD, addiction problems. We are quite excited about these cells and have a published paper coming out about these cells.
We will now be offering an osteoporosis program that will include two of these VSEL treatments a year. Incorporated into these treatments we will utilize a proprietary blend of cytokine growth factors and a supplement program. Both the growth factors and the supplements will also target osteoporosis. Also we will pay for one bone density so that we can track our results.
So the warning should go out to Osteoporosis and Osteopenia. We have targeted them in our gun sites and we are going to assassinate them. More to come Thanks Dr. P
We now know that stem cells can have a very profound effect on the immune system. Understanding the immune system’s role in stem cell biology may help clinicians and scientists better respond to injuries or homeostatic imbalances, as well as develop stem cell therapies to treat diverse ailments. When we are addressing the immune system we are zeroing on a mesenchymal stem cell. These cells are capable of interacting with various types of immune cells, including among others T cells, B cells, natural killer (NK) cells, macrophages, neutrophils, and a host of other cells. These interactions occur through direct cell–cell contact or their specific secretome, which consists of various growth factors and immuno-modulatory factors. Immuno-modulatory factors are those entities which quell the body's immune response in various conditions including osteoarthritis. If the immune response is too strong than repair can not be accomplished. First off, we must clarify something. It is a misnomer to call a mesenchymal stem cells a stem cell. As per the research work of Dr. Arnold Caplan, mesenchymal stem cells really should be considered a medicinal signaling cell. They are like centennials trying to make the stem cell environment more conducive to other cells to accomplish repair. They do this by producing various biochemical compounds effecting the environment. This process is called immuno-modulation. When I lecture I liken mesenchymal stem cells to the body's Navy Seals. They are specialized, get injected into a hostile environment, and probably will not survive. Their job is to secure the area so other stem cells can accomplish repair.
Immune modulation is a concept known to many
Regenerative Medicine stem cell physicians. But when talking about this in more detail they have little knowledge about this. Lets look at things a bit more under the microscope. One major portion of our immune system involves a subset of cells called T cells. B is The above slide is from one of my talks. It shows that our immune system has two major components. The T-1 system which involves cell mediated immunity and the T-2 system which involves Humoral immunity. The (T-1) cell mediated immunity does not involve antibodies but rather actual cells such as types of white blood cells and different growth factors they release. When you have an acute infection various cells will attack the bacteria. On the other hand (T-2) Humoral immunity involves
macromolecules and antibodies found in the body's fluids. This is also called antibody immunity. Humors are the body's fluids. When antibodies are present they attack the bacteria etc.
The real interesting aspects of the cells occurs in the following diagrams. The above diagram shows what mesenchymal cells do in an environment of high levels of inflammatory cytokines. These are typically the "bad guys". They cause pain swelling and inflammation in joints and other portions of the body. In scientific circles they are called IL-1, IL-6, and TNF. What we see by the diagram is that the mesenchymal cells in this environment will cause the release of T-Reg cells and block the formation of T cells. The mesenchymal cells will release a number of good growth factors including IL-10(acts like cortisone without any baggage), Nitric Oxide, and other growth factors. The T cells are many times one of the underlying causes of autoimmune diseases (a process where the body attacks itself). On the other hand the T-reg cells seem to prevent autoimmune diseases from arising. What we can take away from the diagram is that when there is an environment of inflammatory issues the mesenchymal cells stimulate the release of T-reg cells which quell disease issues and at the same time release "good" growth factors which diminish the inflammatory response. When these good growth factors are present they help propagate stem cell survival and
ultimately help correct problems.
In the second diagram we see the opposite situation. In this case there is an environment of low inflammatory cytokines.
The low inflammatory cytokine level encourages the release of T cells. T cells have far reaching effects including the propagation of autoimmune diseases. In the second diagram we see the effects of having low levels of inflammatory cytokines. The mesenchymal cells secrete lower levels of good anti-inflammatory cytokines. In response to low levels of pro-inflammatory cytokines that exist in various chronic diseases, MSCs still produce considerable amounts of chemokines (they attract cells) and adhesion molecules that recruit T cells in close proximity with them. However, they produce only low levels of the immuno-suppressive factors. Thus, the recruited T cells are unchecked and become activated. More importantly the mesenchymal cells help push T cell proliferation. The T cells help autoimmune diseases to flourish. In general they make an environment that is not conducive to stem cell success in correcting a problem.
This is a very elementary view of stem cell and the immune system but it is a good start for the lay person. What do we take away from all of this? As I have stated many times the environment is so important to the success of stem cell treatments. Ultimately, the environment the cells are in control the fate of the stem cells and the success of a treatment. This is why we try in many different ways to alter the environment to allow success in our treatments. Thanks Dr. P.
In a study published with month in the Journal Stem Cells Translational Medicine, researchers from Duke University were able to show that Stem Cells from Umbilical Cord Blood showed significant improvement in children suffering from Autism. The study was conducted as a Phase I Clinical Trial which evaluated primarily the safety of the Stem Cell treatment. However, treatment outcomes were also evaluated.
The study led by Dr. Joanne Kurtzberg from the Robertson Clinical and Translational Cell Therapy Program at Duke University enrolled 25 children aged 2-6 diagnosed with Autism. The researchers used Stem Cells from each child’s preserved Umbilical Cord Blood and delivered them back to the child intravenously. Only a single treatment was provided. Over the course of 12 months following the Stem Cell treatment, the children were examined with behavioral and functional testing. Significant improvements in behavior were found across a wide range of outcome measures in this study. Most of the improvements occurred in the first 6 months after the treatment, and were maintained after 1 year. The treatment was also found to be safe and feasible.
Due to the encouraging results of the study, researchers are planning for larger studies using Umbilical Cord Blood Stem Cells as a potential treatment of Autism.
A new study from the Perelman School of Medicine and University of Pennsylvania published in the Journal Stem Cell this month revealed that adult stem cells that were collected from human fat have the potential to be used in anti-aging treatments. These Stem Cells are referred to as “Adipose Derived Stem Cells” and include a mix of unique Stem Cells commonly available in human fat tissue.
The research study led by Dr. Ivona Percec from the Perleman School of Medicine at the University of Pennsylvania examined the normal aging process of Fat Stem Cells, referred to as “chronological aging”. The study showed that fat stem cells were able to make more proteins as once thought, which gives them the ability to replicate and maintain their stability. “Our study shows these cells are very robust, even when they are collected from older patients,” said Dr. Percec. Compared to other cells such as skin cells (fibroblasts), fat stem cells were able to multiply at the same rate in older and younger individuals.
This finding may imply that these particular stem cells are able to resist the aging process more than others and may be useful as an anti-aging treatment.
As a next step in this ongoing study, researchers are hoping to find ways to make these cells even less resistant to aging by manipulating the stem cell’s DNA structure. Stay tuned for more.
Adipose Derived Stem Cells
Multiple Sclerosis (MS) affects more than 2.3 million people worldwide. It is a progressive autoimmune disease which targets a patient’s neurological system. To date, drugs designed to slow the progression of this debilitating disease have not lived up to their promise.
As an alternative to medications, a patient’s faulty immune system can be eradicated by chemotherapy and then reset by the same patient’s Blood Stem Cells. This treatment is referred to as “Autologous Hematopoietic Stem Cell Transplantation” (AHSCT). In a study published this month in the Journal of the American Medical Association Neurology the authors reviewed data from 281 patients who underwent AHSCT for MS between 1995 to 2006. Most of the patients included in the study had aggressive forms of MS. The study authors led by Dr. Paolo Muraro of the Imperial College of London specifically examined the rate of patient survival and lack of disease progression.
The study results showed a mortality of 2.8%, however almost half (46%) of the patients did not show progression of their symptoms from Multiple Sclerosis. The authors believe the results to be very encouraging and call for further larger scale clinical trials using AHSCT for MS.
Journal Reference:
1. Paolo A. Muraro, MD et al. Long-term Outcomes After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis. JAMA Neurol., February 2017 DOI: 10.1001/jamaneurol.2016.5867
Glioblastoma Cancer Cells
Researchers from the University of North Carolina-Chapel Hill have conducted successful experiments to use Stem Cells as a Cancer fighting tool for an aggressive form of brain cancer. Glioblastoma is one of the deadliest forms of brain cancer, with a median survival of less than 18 months. Currently available treatment options such as surgery, chemotherapy and radiation are generally unsuccessful.
The researchers, led by Dr. Shawn Hingtgen from the department of Neuropathology at the University of North Carolina-Chapel Hill, had inserted human Glioblastoma Cancer Cells into mice. As a next step, the same patient’s skin cells, called “fibroblasts” were converted to Nerve Stem Cells (h-iNSC). This process, by itself, is revolutionary and involves specific, recently discovered proteins, called “transcription factors”. These factors can literally reprogram a patient’s skin cell in the laboratory into a fully functional Nerve Stem Cell, which can then be delivered back to the patient. The process takes only a few days. In the case of this study, the Nerve Stem Cells were also genetically programmed to track and destroy Glioblastoma Cancer Cells.
The study results showed that the specially programmed Nerve Stem Cells were highly efficient at tracking killing the Cancer Cells. The Glioblastoma tumors shrunk 250-fold over the course of 3 weeks, which by itself more than doubled the survivor time. In a related experiment, Dr. Hingtgen and his team used the same Nerve Stem Cells to deliver an additional drug to the Cancer Cells, which further improved the treatment.
The team from the University of North Carolina-Chapel Hill believes that the finding are so convincing and groundbreaking that human trials are only one or two years away. They fully recognize that new treatments for patient afflicted by Glioblastoma are desperately needed. Neural Stem Cells show great promise.
Neural Stem Cells derived from Skin Cells
