The current issue of the STEM CELLS Translational Medicine journal contains a study involving a novel way of increasing the survival rate of stem cells injected into the brain.
Researchers harvested neural stem cells (NSC's) from baby mice and sorted the cells to find a predominance of stem cells containing CD15, a carbohydrate found on the surface of the cells that plays a very important role in cellular migration and adhesion, and in growth factor signaling that helps in cell maintenance and differentiation. This sorting process allowed them to harvest a population of NSC's in which 98% of them were positive for the CD15 marker, approximately six times more than when the sorting method is not used.
These CD15 -positive cells were then differentiated in the lab, eventually resulting in neurons, astrocytes, and oligodendrocytes - these are specific types of cells found in our brain and spinal cord. Neurons are the cells that process and transmit information, astrocytes are the most abundant cells that provide stuctural and metabolic support, and the oligodendrocytes provide support to and insulate our nerve cells. These developed cells were then introduced into the brains of baby mice and studied over time, along with a control group of non-sorted neural cells. Initially, both groups of cells were similar in the baby mice - one week later, when the brain was still growing, the cells in both groups had achieved similar population levels. However, in adult mice the CD15-positive grafts showed significantly higher survival rates. The cells with CD15 also tended to significantly differentiate into oligodendrocytes, cells that have a protective role for neurons.
The significance of this study is that it shows a potential method for improved deliverance of therapeutic cells to our brain and spianl cord. Anthony Atala, MD, edior of the journal and director of the Wake Forest Institute for Regenerative Medicine said "the fact that the CD15-positive cells show a significant increase in oligodendrocyte differentiation suggests that they may be particularly useful for treating diseases involving white matter lesions." White matter lesions are commonly associated with Alzheimer's Disease, multiple sclerosis, and stroke. These types of lesions have also been found with infectious and inflammatory conditions, and even associated with patients experiencing migraine headaches.
Yet another bold step in the research of stem cells and possible therapeutic benefits!
Tuesday, May 21, 2013
Tuesday, April 9, 2013
Arterial Growth
Here are 2 sets of arteriograms (or angiograms, which are x-rays taken with the use of special dyes to visualize arteries):
The left side of both images show very poor arterial blood flow in the leg due to vascular disease. These patients often end up needing amputations due to the lack of blood flow.
The right side of each image shows vastly improved arterial supply after stem cell therapy. The stem cells were injected intramuscularly, meaning into the calf and other lower leg muscles. The stem cells allow for growth of new blood vessels and essentially save these patients' limbs.
Tuesday, April 2, 2013
Case Report #1 - T. M. PATIENT UPDATE
In August of 2012 I wrote about a 35 y.o. female who was our first stem cell orthopedic injection patient (see entry "Case Report #1 - T.M."). She has continued to do extremely well after her treatment and is now over one year out from the procedure. She continues to exercise in a manner that she could not prior to her stem cell therapy, including sports, hiking, and P-90-X. She denies pain and swelling in her right knee, and reports discomfort only in her left knee which has not had a stem cell injection.
On March 7, 2013 she underwent a repeat MRI of her right knee which was then compared to a prior MRI obtained on December 8, 2011.
In the time between the studies, her only treatment was the stem cell injection into the right knee joint which was done in February of 2012. Prior to the cell therapy, this patient's pain was most prominent in the inside aspect of the knee near her knee cap, which coincides with the anterior medial meniscus.
Important excerpts of the recent radiology report read as follows:
"Comparison is made to a prior study of the right knee dated 12/8/2011."
"An improved appearance of the marrow of the distal femur and tibia is noted when compared to the prior study.
Postoperative repair of the anterior horn of the medial meniscus has occurred since the prior exam."
The radiologist did not know that this patient had stem cell therapy, but obviously could detect changes that showed improvement in her primary orthopedic issue. We are very pleased to share these MRI findings and the fact that the radiologist saw evidence of meniscal repair.
On March 7, 2013 she underwent a repeat MRI of her right knee which was then compared to a prior MRI obtained on December 8, 2011.
In the time between the studies, her only treatment was the stem cell injection into the right knee joint which was done in February of 2012. Prior to the cell therapy, this patient's pain was most prominent in the inside aspect of the knee near her knee cap, which coincides with the anterior medial meniscus.
Important excerpts of the recent radiology report read as follows:
"Comparison is made to a prior study of the right knee dated 12/8/2011."
"An improved appearance of the marrow of the distal femur and tibia is noted when compared to the prior study.
Postoperative repair of the anterior horn of the medial meniscus has occurred since the prior exam."
The radiologist did not know that this patient had stem cell therapy, but obviously could detect changes that showed improvement in her primary orthopedic issue. We are very pleased to share these MRI findings and the fact that the radiologist saw evidence of meniscal repair.
Thursday, March 21, 2013
The Basics - What Exactly Is A Stem Cell?
A very common question happens to be one that goes back to the basics - what is a stem cell?
Stem cells are essentially building blocks that are found in all multicellular organisms. These cells can divide (through a process called mitosis), self renew, and differentiate into many different cell types.
Again, the classic definition of a stem cell requires that it possess the following properties:
In general, there are two broad types of stem cells: embryonic, which are isolated from blastocysts (a product of early gestation that leads to the development of the embryo), and adult stem cells, found in various tissues throughout the body. In the developing embryo, stem cells can differentiate into all specialized cells (these are called pluripotent cells) and also maintain the normal turnover of regenerative organs/tissues, such as blood, skin, or intestinal tissues. In adults, stem cells serve as the repair system for the body, replenishing adult tissues after injury or through the normal process of aging. Adult stem cells are multipotent, meaning they can differentiate into many cell types, but not all.
There are three readily-accessible sources of autologous (meaning from one's own body) adult stem cells in humans:
1. Bone marrow - requires extraction by drilling into bone (typically the iliac crest)
2. Adipose tissue (fat) - requires extraction by liposuction
3. Blood - requires extraction through the process of pheresis, wherein blood is drawn from the donor, passed through a machine that extracts the stem cells, then returns other portions of the blood back to the donor
Stem cells can also be found in umbilical cord blood just after birth.
Autologous harvesting involves the least risk when working with stem cells, as the cells are obtained from the patient's own body. Thus, there is no chance of an auto-immune reaction or tissue rejection. This also eliminates the risk of acquring an infection from another person.
Stem cells are essentially building blocks that are found in all multicellular organisms. These cells can divide (through a process called mitosis), self renew, and differentiate into many different cell types.
Again, the classic definition of a stem cell requires that it possess the following properties:
- Self-renewal: the ability to go through continued cycles of cell division while maintaining the undifferentiated state.
- Potency: the ability to differentiate into specialized cell types.
In general, there are two broad types of stem cells: embryonic, which are isolated from blastocysts (a product of early gestation that leads to the development of the embryo), and adult stem cells, found in various tissues throughout the body. In the developing embryo, stem cells can differentiate into all specialized cells (these are called pluripotent cells) and also maintain the normal turnover of regenerative organs/tissues, such as blood, skin, or intestinal tissues. In adults, stem cells serve as the repair system for the body, replenishing adult tissues after injury or through the normal process of aging. Adult stem cells are multipotent, meaning they can differentiate into many cell types, but not all.
There are three readily-accessible sources of autologous (meaning from one's own body) adult stem cells in humans:
1. Bone marrow - requires extraction by drilling into bone (typically the iliac crest)
2. Adipose tissue (fat) - requires extraction by liposuction
3. Blood - requires extraction through the process of pheresis, wherein blood is drawn from the donor, passed through a machine that extracts the stem cells, then returns other portions of the blood back to the donor
Stem cells can also be found in umbilical cord blood just after birth.
Autologous harvesting involves the least risk when working with stem cells, as the cells are obtained from the patient's own body. Thus, there is no chance of an auto-immune reaction or tissue rejection. This also eliminates the risk of acquring an infection from another person.
Thursday, February 14, 2013
Stem Cells and Heart Function
On November 6, 2012, at the American Heart Association Scientific Sessions meeting, Drs. Bolli (from the University of Louisville) and Anversa (from Brigham and Women's Hospital in Boston) presented updated data from their SCIPIO trial (Stem Cell Infusion in Patients with Ischemic CardiomyOpathy). This trial was a randomized open-label trial using cardiac stem cells in patients with heart failure after a heart attack, or myocardial infarction. The data they presented was the follow-up after 2 years.
The trial followed 33 patients who suffered a heart attack with measurable damage to the cardiac muscle. The patients all had a decreased LVEF (left ventricular ejection fraction), a standard measure of the heart's function measuring the blood ejected from the left ventricle during contraction of the heart muscle. In the study, the patients' LVEF had to be equal to or under 40%, with a normal LVEF being 50% or more. The trial involved harvesting patients' stem cells from their hearts during coronary artery bypass surgery and then multiplying these cells in the research team's lab. When approximately 1 million cells had been produced, the stem cells were then reintroduced into the region of the heart that had been scarred as a result of the heart attack.
Of the 33 patients, 20 actually received the stem cell therapy while the other 13 were in the control group receiving no stem cells. The researchers report that the 20 patients receiving stem cell therapy had marked improvement in cardiac function. Four months after the stem cell infusion, these pateints' average LVEF rose from 29% to 36%. At the one year mark, LVEF increased by 8.1%, while at the 2 year mark by 12.9%. The 13 control patients showed no improvement, on average.
Additionally, nine of the patients who received stem cells underwent MRI's and showed marked reduction in the size of the heart muscle scarring and resultant increase in viable muscle tissue. On average, the infarct size was 33.9 grams prior to treatment and 18.2 grams at the 2 year mark. The viable left ventricle tissue rose from 146.3 to 164.2 grams.
One patient in particular had suffered from two heart attacks prior to the study. His LVEF went from 38% to 58% after stem cell therapy, with his heart now showing essentially no ill effects from the prior myocardial infarctions.
The investigators plan to continue following these patients for two more years, and hopefully expand their resaerch with further funding.
The trial followed 33 patients who suffered a heart attack with measurable damage to the cardiac muscle. The patients all had a decreased LVEF (left ventricular ejection fraction), a standard measure of the heart's function measuring the blood ejected from the left ventricle during contraction of the heart muscle. In the study, the patients' LVEF had to be equal to or under 40%, with a normal LVEF being 50% or more. The trial involved harvesting patients' stem cells from their hearts during coronary artery bypass surgery and then multiplying these cells in the research team's lab. When approximately 1 million cells had been produced, the stem cells were then reintroduced into the region of the heart that had been scarred as a result of the heart attack.
Of the 33 patients, 20 actually received the stem cell therapy while the other 13 were in the control group receiving no stem cells. The researchers report that the 20 patients receiving stem cell therapy had marked improvement in cardiac function. Four months after the stem cell infusion, these pateints' average LVEF rose from 29% to 36%. At the one year mark, LVEF increased by 8.1%, while at the 2 year mark by 12.9%. The 13 control patients showed no improvement, on average.
Additionally, nine of the patients who received stem cells underwent MRI's and showed marked reduction in the size of the heart muscle scarring and resultant increase in viable muscle tissue. On average, the infarct size was 33.9 grams prior to treatment and 18.2 grams at the 2 year mark. The viable left ventricle tissue rose from 146.3 to 164.2 grams.
One patient in particular had suffered from two heart attacks prior to the study. His LVEF went from 38% to 58% after stem cell therapy, with his heart now showing essentially no ill effects from the prior myocardial infarctions.
The investigators plan to continue following these patients for two more years, and hopefully expand their resaerch with further funding.
Friday, December 7, 2012
Stem Cells to Treat Alzheimer's Disease
A recent article in the December, 2012 issue of Stem Cells by Chen and Burton-Jones describes potential stem cell treatments for Alzheimer's disease (AD), as well as the use of stem cells to model and investigate the disease. They offer encouraging information on how stem cells might play a part in future therapy, based on a number of past and ongoing research studies.
Alzheimer's disease is the most common type of age-related dementia that affects over 5 million people in the U.S., with projections that 115 million people worldwide may develop dementia by the year 2050. Current treatment modalities provide no long-term benefits, even after extensive research for many years.
Stem cell treatment options have been under investigation using animal studies, with some enlightening findings so far. For the majority of diseases and disorders that are treated with stem cells, the therapy is aimed at replacing missing or degenerative cells with new ones. In the case of AD, that type of treatment would not be likely to produce a benefit, as a number of neuronal systems and neurotransmitter phenotypes can be affected and cell replacement would not be viable. Too many types of nerves are involved, along with the complex systems of connectivity, much of which develops in utero. Therefore, cell replacement would not seem to offer benefit with such a diffuse set of problems that are encountered in AD.
So how could stem cells be of benefit? Well, the benefits seem to come through indirect means. One of the problems found in AD is a loss of synapses. This loss seems to correlate most tightly with the dementia process. The number of synapses and their relative strength appears to be closely regulated by a select group of neurotrophins, groups of secreted proteins that induce the development, function, and survival of neurons. These are essentially growth factors for our nervous system. Stem cells can induce high levels of these growth hormones, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this way, stem cell therapy might allow for delivery of these proteins to the disease-affected areas of the brain and thus possibly increasing neuronal survival.
Another known factor in AD is chronic inflammation. Stem cells can have anti-inflammatory properties, as certain stem cell populations have been shown to induce the expression of anti-inflammatory factors, specifically interleukin-10 and prostaglandin E2. There are mice studies that have shown improved cognition and improved pathology due to apparent attenuation of the inflammatory process after treatment with stem cells. However, it is not known how this will translate to human patients, if at all, as prior clinical trials with anti-inflammatory drugs have shown no benefit in patients with AD.
Another potential way that stem cells could provide some benefit is by delivering therapeutic proteins to the damaged areas in the brain, as prior studies have shown the ability of stem cells to migrate throughout the brain and focus on regions damaged by injury and/or inflammation. What is not yet known is how much of an effect the underlying pathology plays on this response, as the severity of the disease might influence the likelihood of success, along with unknowns surrounding the lifespan of engrafted cells, the patient's immune response, and even the source of the cells and proteins.
As the excitement grows related to the possibilities, caution must be encouraged as more studies need to be undertaken. Difficulties exist in researching treatment options for AD, as no long term human studies have taken place. Stem cells may prove quite useful in studying the AD process, as stem cell lines can be elicited that exhibit known AD-associated genes. This will allow for researchers to focus on the differences between the normal and pathogenic function of these genes.In this way, stem cells may hold the key to learning more about the disorder and to eventually treating it.
Alzheimer's disease is the most common type of age-related dementia that affects over 5 million people in the U.S., with projections that 115 million people worldwide may develop dementia by the year 2050. Current treatment modalities provide no long-term benefits, even after extensive research for many years.
Stem cell treatment options have been under investigation using animal studies, with some enlightening findings so far. For the majority of diseases and disorders that are treated with stem cells, the therapy is aimed at replacing missing or degenerative cells with new ones. In the case of AD, that type of treatment would not be likely to produce a benefit, as a number of neuronal systems and neurotransmitter phenotypes can be affected and cell replacement would not be viable. Too many types of nerves are involved, along with the complex systems of connectivity, much of which develops in utero. Therefore, cell replacement would not seem to offer benefit with such a diffuse set of problems that are encountered in AD.
So how could stem cells be of benefit? Well, the benefits seem to come through indirect means. One of the problems found in AD is a loss of synapses. This loss seems to correlate most tightly with the dementia process. The number of synapses and their relative strength appears to be closely regulated by a select group of neurotrophins, groups of secreted proteins that induce the development, function, and survival of neurons. These are essentially growth factors for our nervous system. Stem cells can induce high levels of these growth hormones, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this way, stem cell therapy might allow for delivery of these proteins to the disease-affected areas of the brain and thus possibly increasing neuronal survival.
Another known factor in AD is chronic inflammation. Stem cells can have anti-inflammatory properties, as certain stem cell populations have been shown to induce the expression of anti-inflammatory factors, specifically interleukin-10 and prostaglandin E2. There are mice studies that have shown improved cognition and improved pathology due to apparent attenuation of the inflammatory process after treatment with stem cells. However, it is not known how this will translate to human patients, if at all, as prior clinical trials with anti-inflammatory drugs have shown no benefit in patients with AD.
Another potential way that stem cells could provide some benefit is by delivering therapeutic proteins to the damaged areas in the brain, as prior studies have shown the ability of stem cells to migrate throughout the brain and focus on regions damaged by injury and/or inflammation. What is not yet known is how much of an effect the underlying pathology plays on this response, as the severity of the disease might influence the likelihood of success, along with unknowns surrounding the lifespan of engrafted cells, the patient's immune response, and even the source of the cells and proteins.
As the excitement grows related to the possibilities, caution must be encouraged as more studies need to be undertaken. Difficulties exist in researching treatment options for AD, as no long term human studies have taken place. Stem cells may prove quite useful in studying the AD process, as stem cell lines can be elicited that exhibit known AD-associated genes. This will allow for researchers to focus on the differences between the normal and pathogenic function of these genes.In this way, stem cells may hold the key to learning more about the disorder and to eventually treating it.
Thursday, November 29, 2012
Stem Cells / PRP in Tendon Injuries
Tendons are highly prone to injury due to their inherent design and function. Relative to other structures, tendons are hypovascular, meaning they have a poor blood supply. Tendons typically have a cross-sectional area that is significantly less than the in-line muscle, and therefore, considerable stress is placed on the tendon, especially during exercise. The primary function of a tendon is to transmit the force of muscular contraction to the skeletal system, thereby generating movement. It is this mechanical force that can lead to excessive stress that causes injury.
Due to these factors, tendons are frequently injured, and the natural healing response is slow and inefficient. The 1999 publication Musculoskeletal Conditions in the United States by Praemer, Furner, & Rice, estimates that $30 billion is spent in the U.S. each year on musculoskeletal injuries, and approximately 45% of these are tendon and/or ligament injuries. In an effort to show just how common tendon injuries are, an article by Sher, et. al., in 1995 entitled "Abnormal findings on magnetic resonance images of asymptomatic shoulders" found an overall incidence of shoulder rotator cuff tears to be 34% across all age groups, even though these patients all had no pain and exhibited normal functional activity. The percentage was smaller in younger patients and increased with advancing age, as 54% of the patients over the age of 60 had cuff tears.
Surgical repair of tendon injuries has become increasingly more common, although such repairs are often unsuccessful. Bishop, et. al., published a study in 2006 called "Cuff integrity after arthroscopic versus open rotator cuff repair: a prospective study" in which they conclude that while small cuff tears have reasonable surgical outcomes, large tears show failure rates up to 75%. Thus, traditional surgey is no guarantee of restored function and elimination of pain.
One factor in the difficult recovery from a tendon injury is that scarring can occur during the healing process. The area of the tendon that scars is never able to be as fully functional as it once was, and is even more prone to re-injury. This is an important advantage in treating this type of injury with stem cells, as the stem cells can be used by the body to grow new tendon instead of scar tissue. This then leads to a functionally superior outcome.
We believe that dual treatment with stem cells (for the reason listed above) and platelet rich plasma (PRP) offers the best possible solution. The stem cells will be used as the body needs them to regenerate tendon, while the PRP gives concentrated growth factors and platelets directly to the site of injury to promote healing. This tecnique is not only useful for rotator cuff treatment, but can be used for any tendon injury (Achilles, "tennis elbow", other shoulder tendons, etc.).
Due to these factors, tendons are frequently injured, and the natural healing response is slow and inefficient. The 1999 publication Musculoskeletal Conditions in the United States by Praemer, Furner, & Rice, estimates that $30 billion is spent in the U.S. each year on musculoskeletal injuries, and approximately 45% of these are tendon and/or ligament injuries. In an effort to show just how common tendon injuries are, an article by Sher, et. al., in 1995 entitled "Abnormal findings on magnetic resonance images of asymptomatic shoulders" found an overall incidence of shoulder rotator cuff tears to be 34% across all age groups, even though these patients all had no pain and exhibited normal functional activity. The percentage was smaller in younger patients and increased with advancing age, as 54% of the patients over the age of 60 had cuff tears.
Surgical repair of tendon injuries has become increasingly more common, although such repairs are often unsuccessful. Bishop, et. al., published a study in 2006 called "Cuff integrity after arthroscopic versus open rotator cuff repair: a prospective study" in which they conclude that while small cuff tears have reasonable surgical outcomes, large tears show failure rates up to 75%. Thus, traditional surgey is no guarantee of restored function and elimination of pain.
One factor in the difficult recovery from a tendon injury is that scarring can occur during the healing process. The area of the tendon that scars is never able to be as fully functional as it once was, and is even more prone to re-injury. This is an important advantage in treating this type of injury with stem cells, as the stem cells can be used by the body to grow new tendon instead of scar tissue. This then leads to a functionally superior outcome.
We believe that dual treatment with stem cells (for the reason listed above) and platelet rich plasma (PRP) offers the best possible solution. The stem cells will be used as the body needs them to regenerate tendon, while the PRP gives concentrated growth factors and platelets directly to the site of injury to promote healing. This tecnique is not only useful for rotator cuff treatment, but can be used for any tendon injury (Achilles, "tennis elbow", other shoulder tendons, etc.).
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