While high-dose immunosuppressive therapy is not without complications, we must remember that research is rarely linear and every step closer is a step closer – we learn a bit more and refine the process with each step as our understanding of all of the elements which make up our health, recover and illness are slowly puzzled together like a patch-work quilt…
Encouraging results help set stage for larger studies.
New clinical trial results provide evidence that high-dose immunosuppressive therapy followed by transplantation of a person’s own blood-forming stem cells can induce sustained remission of relapsing-remitting multiple sclerosis (MS), an autoimmune disease in which the immune system attacks the central nervous system.
Five years after receiving the treatment, called high-dose immunosuppressive therapy and autologous hematopoietic cell transplant (HDIT/HCT), 69 percent of trial participants had survived without experiencing progression of disability, relapse of MS symptoms or new brain lesions. Notably, participants did not take any MS medications after receiving HDIT/HCT. Other studies have indicated that currently available MS drugs have lower success rates.
The trial, called HALT-MS, was sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and conducted by the NIAID-funded Immune Tolerance Network (ITN). The researchers published three-year results from the study in December 2014, and the final five-year results appear online Feb. 1 in Neurology, the medical journal of the American Academy of Neurology.
Let’s take a page out of what was not too long ago science fiction; which is now science-fact.
A pancreas was grown in a rat,
the organ was transplanted into a mouse,
the mouse was given immunosuppressive therapy to prevent rejection,
the diabetic mice were able to normalize their blood glucose levels for over a year.
This illustrates the long proven regenerative capacity of stem cells and the recent advancements scientists have made with anti-rejection protocols…And of course, the cool inter-species transplant of rat to mouse.
Rat-grown mouse pancreases help reverse diabetes in mice
Growing organs from one species in the body of another may one day relieve transplant shortages. Now researchers show that islets from rat-grown mouse pancreases can reverse disease when transplanted into diabetic mice.
A rat in which researchers were able to grow a mouse pancreas. Islets from the pancreases were transplanted into mice with diabetes. The transplants helped control the mice’s blood sugar levels. Courtesy of the Nakauchi lab
The recipient animals required only days of immunosuppressive therapy to prevent rejection of the genetically matched organ rather than lifelong treatment.
The success of the interspecies transplantation suggests that a similar technique could one day be used to generate matched, transplantable human organs in large animals like pigs and sheep.
To conduct the work, the researchers implanted mouse pluripotent stem cells, which can become any cell in the body, into early rat embryos. The rats had been genetically engineered to be unable to develop their own pancreas and were thus forced to rely on the mouse cells for the development of the organ.
Once the rats were born and grown, the researchers transplanted the insulin-producing cells, which cluster together in groups called islets, from the rat-grown pancreases into mice genetically matched to the stem cells that formed the pancreas. These mice had been given a drug to cause them to develop diabetes.
“We found that the diabetic mice were able to normalize their blood glucose levels for over a year after the transplantation of as few as 100 of these islets,” said Hiromitsu Nakauchi, MD, PhD, a professor of genetics at Stanford. “Furthermore, the recipient animals only needed treatment with immunosuppressive drugs for five days after transplantation, rather than the ongoing immunosuppression that would be needed for unmatched organs.”
Nakauchi, who is a member of Stanford’s Institute for Stem Cell Biology and Regenerative Medicine, is the senior author of a paper describing the findings, which was published online Jan. 25 in Nature. Tomoyuki Yamaguchi, PhD, an associate professor of stem cell therapy, and researcher Hideyuki Sato, both from the University of Tokyo, share lead authorship of the paper.
Although much research remains to be done, scientist Hiromitsu Nakauchi and his colleagues believe their work with rodents shows that a similar technique could one day be used to generate matched, transplantable human organs in large animals like pigs and sheep. Wing Hon Films
Organs in short supply
About 76,000 people in the United States are currently waiting for an organ transplant, but organs are in short supply. Generating genetically matched human organs in large animals could relieve the shortage and release transplant recipients from the need for lifelong immunosuppression, the researchers say.
People suffering from diabetes could also benefit from this approach. Diabetes is a life-threating metabolic disease in which a person or animal is unable to either make or respond appropriately to insulin, which is a hormone that allows the body to regulate its blood sugar levels in response to meals or fasting. The disease affects hundreds of millions of people worldwide and is increasing in prevalence. The transplantation of functional islets from healthy pancreases has been shown to be a potentially viable option to treat diabetes in humans, as long as rejection can be avoided.
The researchers’ current findings come on the heels of a previous study in which they grew rat pancreases in mice. Although the organs appeared functional, they were the size of a normal mouse pancreas rather than a larger rat pancreas. As a result, there were not enough functional islets in the smaller organs to successfully reverse diabetes in rats.
Mouse pancreases grown in rats
In the current study, the researchers swapped the animals’ roles, growing mouse pancreases in rats engineered to lack the organ. The pancreases were able to successfully regulate the rats’ blood sugar levels, indicating they were functioning normally. Rejection of the mouse pancreases by the rats’ immune systems was uncommon because the mouse cells were injected into the rat embryo prior to the development of immune tolerance, which is a period during development when the immune system is trained to recognize its own tissues as “self.” Most of these mouse-derived organs grew to the size expected for a rat pancreas, rendering enough individual islets for transplantation
Next, the researchers transplanted 100 islets from the rat-grown pancreases back into mice with diabetes. Subsequently, these mice were able to successfully control their blood sugar levels for over 370 days, the researchers found.
Because the transplanted islets contained some contaminating rat cells, the researchers treated each recipient mouse with immunosuppressive drugs for five days after transplant. After this time, however, the immunosuppression was stopped.
After about 10 months, the researchers removed the islets from a subset of the mice for inspection.
“We examined them closely for the presence of any rat cells, but we found that the mouse’s immune system had eliminated them,” said Nakauchi. “This is very promising for our hope to transplant human organs grown in animals because it suggests that any contaminating animal cells could be eliminated by the patient’s immune system after transplant.”
Importantly, the researchers also did not see any signs of tumor formation or other abnormalities caused by the pluripotent mouse stem cells that formed the islets. Tumor formation is often a concern when pluripotent stem cells are used in an animal due to the cells’ remarkable developmental plasticity. The researchers believe the lack of any signs of cancer is likely due to the fact that the mouse pluripotent stem cells were guided to generate a pancreas within the developing rat embryo, rather than coaxed to develop into islet cells in the laboratory. The researchers are working on similar animal-to-animal experiments to generate kidneys, livers and lungs.
Although the findings provide proof-of-principle for future work, much research remains to be done. Ethical considerations are also important when human stem cells are transplanted into animal embryos, the researchers acknowledge.
There’s a lot going on in this article. 14 patients with Down Syndrome were treated with stem cells. Down Syndrome is a common chromosomal disorder caused by trisomy of chromosome 21 (HSA21q). I’m not going to introduce a critical analysis of this. This article does that with great skepticism. Let’s take a different tact. Let’s approach this with the idea that it could happen but we don’t yet know how. How about I raise some questions of my own with the intention to not tear down but rather to perhaps, inspire someone else to discover a new path to some answers. Let’s throw away conventional thought and limitations and try to grasp a kernel of truth from a bag of confusion. I’m going to blue sky here… Blue Sky: adjective – using the imagination to think of ideas that do not yet have practical uses or make money.
How can stem cells possibly modify a genetic disorder? Maybe they can’t, but maybe they can. Epigenetics tells us that our gene expressions are constantly changing and our concept of what can and can’t change in the human body is constantly evolving. Are the stem cells modifying the chromosome? Conventional science would indicate that this is impossible. But maybe we are seeing the results from a change in phenotype without a change in genotype. 15 years ago, conventional science was positive that heart cells couldn’t regenerate either. We still have an enormous amount to learn. Perhaps our genetics are even less stable than we thought?
Non-scientist gene therapy? Gene therapy is a technique that uses genes to treat or prevent disease. Three techniques of gene therapy are:
Replacing a mutated gene that causes disease with a healthy copy of the gene.
Inactivating, or “knocking out,” a mutated gene that is functioning improperly.
Introducing a new gene into the body to help fight a disease.
Is it so far fetched to imagine that the stem cells can do already what scientists do? We know stem cells can heal and regenerate. Why not also perform gene therapy? We’ve seen modified allogeneic stem cells recover fetuses (in the womb) from the genetic disorder of severe osteogenesis imperfecta before 2005. 1, 2 We know stem cells can regrow finger tips in kids under 8, become skin cells and then if not needed, reverting back to a nascent state and becoming nail cells and then reverting back, etc. So maybe they can modify at the genetic level too, but how?
What’s mine is…yours? (The Good, The Bad and the Ugly) What needs to happen to modify genetics? Not the science, but the logic. The stem cells would need to recognize that the chromosomal disorder is atypical – an aberrant construct needing modification – and then change it towards a different paradigm. Maybe they can do that because the cells used are from someone else (allogenic) – so perhaps the stem cells carry the blue prints and adhere to the donor’s physiology?The donor’s physiology then, becomes the road map, the standard which the stem cells are healing the patient towards. The “normal standard,” so to speak. It makes some sense as, often, in allogenic stem cell treatment scenarios (Embryonic and induced Pluripotent for example), the genetic anomalies of the donor influence the recipient. So if the negative elements within the donor can influence the patient, why not the positive? Why wouldn’t the relative genetic normalcies of the donor influence the physiology of the recipient?
An improvement by any other name would smell just as sweet?‘“He started babbling and crawling, and his facial features underwent a change.” The boy, who lives in Singapore, is now 3 years old. “He continues to develop age-appropriate skills,” says Titus.’
If the indicators and symptoms of Down Syndrome reduced or went away and they ARE tied to the genetics, how did that happen? If the indicators and symptoms of Down Syndrome reduced or went away and they are NOT tied to the genetics, maybe the connections between the cause and the result is not as rigid as we thought. Can someone have the chromosomal variant of Down Syndrome but have no indicators and no symptoms? Something very worthwhile to work towards. Perhaps we have to expand our view of what it means to recover from an illness beyond just reversing the criteria we currently use to define the disease.
What if everything else in the body works better due to the stem cells? The circulatory system, the GI, the neurological, the lymph and all of ancillary parts and pieces work better resulting in a greater capacity for learning, growth, development, etc. We know the central nervous system does regenerate as well as the brain, though very slowly; so if you can improve the workings of every part of the body, even without addressing the additional chromosome issue of Down Syndrome, wouldn’t that potentially result in the smartest, strongest, healthiest person with Down Syndrome? Isn’t that significant improvement?
If you were diagnosed with cancer but there was a simple treatment which would allow you to have no symptoms and you could live a full and complete life; curing cancer wouldn’t really matter to you, would it? That goal would cease to be our priority. Now we are shifting from disease mitigation to quantifiable improvements in the measurable criteria by which the Down Syndrome patient is defined. Maybe negating the symptoms and the ramifications of a disease is equal in importance to curing it. Maybe it is even easier to do and the patient won’t be able to tell the difference between the two. The patient; healthier, better, with fewer or no symptoms. Isn’t that what we are all working towards anyway?
IS that what we are all working towards? Survey says… The Purist says: “Scam! You can’t fix genetic conditions. You didn’t fix the Down Syndrome!” The Parent says: “My child’s ability to xyz has improved! They are at age level in school and on height and weight and on and on…” The Prognosis says: “Patient presents with fewer or none of the indicators and symptoms commonly associated with Down Syndrome and what is exhibited is more mild in nature.” The Pragmatist says:“This advancement in therapies for Down Syndrome allows the patient to live a normal life, unburdened by the symptoms and long term ramifications of the disease.” The Future says: “We have seen a lower incidence of the common conditions associated with this Down Syndrome – various congenital and progressive medical conditions such as mental retardation, congenital heart disease, gastrointestinal anomalies, skeletal anomalies, leukemia and Alzheimer’s disease.”
Adverse side affects? The cells used were Human Embryonic stem cells. Now, they are very powerful as they have the capacity to differentiate into the hundreds of cells in the human body…but they also have a history of rejection and cysts and tumors which can become cancerous. This is an area of great concern and I am very curious as to how the doctors addressed these issues or felt they were insignificant. This issue needs more research…
Taoist philosophy says: ‘“Water always seeks the easiest path, the common level of life. When it reaches a spot where there is a blockage, water finds the easiest path around the blockage. Or, if it can’t find a way around the blockage, it continues to assemble. The water gets deeper and deeper until finally the level increases and it flows over the blockage. It uses itself to go beyond whatever it needs to go beyond.” Eventually, water wears down even the hardest rock. Proof of this is seen in the Grand Canyon. The power of water may not be evident right away; over time, though, the massive mountain is worn away while the stream remains.’ Go around. Go over. Go through. Each has it’s merits and disadvantages. Let’s pursue all as viable paths for the healing of the patient.
Most would argue that stem cells encompass the most significant change to disease treatment and medicine in all history. Stem cells are a game changer. THE game changer.
If stem cells are the game changer…
maybe it’s past time we changed HOW WE KEEP SCORE.
Clinic claims it has used stem cells to treat Down’s syndrome
A clinic in India says it has used stem cells to treat Down’s syndrome in up to 14 people, but the announcement has alarmed independent researchers
A CLINIC claims it has used stem cells to treat Down’s syndrome in up to 14 people. “As far as we know, it’s the first time that stem cells have been used to treat Down’s syndrome,” says Jyoti Titus, manager at Nutech Mediworld clinic in New Delhi, India.
The announcement has set alarm bells ringing. It’s not clear to independent stem cell or Down’s experts how stem cells – which can form many types of tissue – might treat Down’s, a genetic disorder caused by having an extra chromosome.
Down’s: an extra chromosome 21 – Department of Clinical Cytogenetics, Addenbrookes Hospital/Science Photo Library
“The use of these cells does not make biological sense and may place the babies at considerable risk of side effects,”says John Rasko of the International Society for Cellular Therapy.
Clinically proven stem cell therapies are only just starting to become available. The first off-the-shelf stem cell treatment to gain regulatory approval was launched in Japan last year, and prevents transplanted organs from attacking their recipients. A number of research teams are putting other experimental stem cell therapies through stringent clinical trials.
But hundreds of clinics worldwide already offer stem cell treatments unvetted by regulatory authorities. A patent held by the clinic’s medical director, Geeta Shroff, from 2007 suggests that the cells offered by Nutech Mediworld could be helpful for over 70 types of conditions, from Down’s syndrome to Alzheimer’s disease, and even vegetative states.
“The use of stem cells doesn’t make sense and may place the babies at considerable risk”
Most treatments for children with Down’s syndrome centre on support – including speech and behavioural therapies. But in a study published last year Shroff, reported that a baby with Down’s syndrome developed better understanding, improved limb muscle tone, and the ability to recognise his relatives after receiving stem cells (Journal of Medical Cases, doi.org/bx3v).
“There’s no comparison to similar individuals with Down’s syndrome, and no indication this therapy had any effect whatsoever, so the author has no basis at all for saying the injections were beneficial,” says Elizabeth Fisher at University College London.
But since no other treatment was given, it is evident that the child’s improvements were due to stem cell treatment, says Titus. “He started babbling and crawling, and his facial features underwent a change.” The boy, who lives in Singapore, is now 3 years old. “He continues to develop age-appropriate skills,” says Titus.
Shroff’s study says she injected the cells, developed from a donated embryo, into his blood, back muscles and under his skin, as well as giving them as a nasal spray. “Stem cells have an innate ability to repair and regenerate, and that is how the baby’s condition improved,” says Titus.
“There’s no obvious way in which this treatment would have worked,” says Victor Tybulewicz at the Francis Crick Institute in London. To have any effect, neural stem cells would need to be injected into the brain, he says.
“The author appears to have no idea of where [the cells] are going, or what they’re doing,” says Fisher. “It’s even worse now we know they’ve treated 14 patients, not just one.”
Titus says that the way the cells were developed means recipients don’t need immunosuppressants. But Tybulewicz disagrees. “I expect the most likely outcome of the injections would have been that they were recognised as foreign and eliminated by the immune system,” he says. More details of the biological impact of the stem cells will be revealed in a study that has been submitted for publication, says Titus.
Nutech Mediworld isn’t the only clinic offering stem cells. An analysis led by Rasko last year identified 417 unique websites advertising stem cell treatments directly to patients. Of these, 187 were linked to 215 clinics in the US. Thirty-five websites were linked to organisations in India.
Although India introduced national guidelines on clinical stem cell research and treatments a decade ago, these are not legally binding.
This article appeared in print under the headline “Clinic claims stem cells treat Down’s syndrome”
A little over a week ago, I posted an article that described:
Of the 100 million BULK CANCER CELLS in a 1-cm cancer tumor, there are about 1,000 to 10,000 CANCER STEM CELLS and those cells are up to 15 times more active and may be the only cells responsible for cancer cell reproduction and metastasis.
Scientists have zeroed in even deeper and targeted a new ‘CD99’ molecule expressed on certain stem cells that drive human leukemia malignancies. They’ve designed antibodies that can directly kill human acute myeloid leukemia (AML) stem cells.
protein-sugar molecule, CD99
Researchers design antibody that recognizes and destroys blood cancer stem cells
Published on January 25, 2017 at 9:44 PM·
A protein-sugar molecule, CD99, occurs more frequently than normal on stem cells responsible for blood cancers, including acute myeloid leukemia (AML) and the related myelodysplastic syndromes (MDS).
This is the finding of a study led by researchers from NYU Langone Medical Center and Memorial Sloan Kettering Cancer Center, and published online Jan. 25 in Science Translational Medicine.
Building on this discovery, the study authors designed an antibody that recognizes and destroys CD99-covered leukemia cells while sparing normal blood stem cells, a finding confirmed by experiments in human cells and in mice with AML cells. Antibodies are immune system proteins that stick to a specific target, like a protein on the surface of invading bacterium. In recent years, researchers have become capable of engineering antibodies so that they target disease-related molecules.
“Our findings not only identify a new molecule expressed on stem cells that drive these human malignancies, but we show that antibodies against this target can directly kill human AML stem cells,” says corresponding study author, Christopher Y. Park, MD, PhD, associate professor in the Department of Pathology at NYU Langone and its Perlmutter Cancer Center.
“While we still have important details to work out, CD99 is likely to be an exploitable therapeutic target for most AML and MDS patients, and we are working urgently to finalize a therapy for human testing,” says Park.
Direct Cell Killing
Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) arise from abnormal stem cells that build up in bone marrow until they interfere with normal blood cell production. Patients struggle with anemia, increased risk for infection, and bleeding.
The study results are based on the understanding that cancers, like normal tissues, contain stem cells that give rise to all the other cells. Such “cancer stem cells” are known to be major drivers of many cancer types. In AML, a small group of leukemic stem cells become incapable of maturing into red or white blood cells as intended. Most leukemias respond initially to standard treatment, but relapse is common as standard treatments fail to kill leukemia stem cells, which continue to multiply.
The research team became interested in CD99 when they observed that it occurs frequently on AML and MDS cells, and then noted in the literature that CD99 is elevated in a rare bone cancer called Ewing’s Sarcoma. This prompted them to see if CD99 was important in the development of these blood diseases.
When researchers examined stem cell populations from 79 AML and 24 MDS patients, they found that approximately 85 percent of stem cells in both groups expressed high levels of CD99. The levels were so high that diseased stem cells could be cleanly separated from related, normal stem cells in AML patients.
Upon confirming that CD99 was abundant on leukemia stem cells, the research team then made several CD99 antibodies, and chose to focus on the one that most effectively killed those cells. Researchers found that when the study antibody attaches itself to CD99 on the surface of a cancer stem cell, it sends a signal inside the cell that increases the activity of enzymes called SRC-family kinases.
While the team does not yet know why, the binding of their antibody to CD99, and the subsequent activation of these enzymes, causes leukemia stem cells to die. Most cells with genetic mistakes leading to cancer “sense” they are flawed and self-destruct, but CD99, so the theory goes, may be part of a mechanism that prevents this. As the antibody binds to CD99, it appears to undo this block on self-destruction.
“With the appropriate support, we believe we can rapidly determine the best antibodies for use in patients, produce them at the quality needed to verify our results, and apply for permission to begin clinical trials,” says Park.
While the most common acute leukemia affecting adults (22,000 new cases each year) and expected to become more prevalent as the population ages, AML it is still relatively rare, accounting for 1.2 percent of U.S. cancer deaths. About 15,000 mostly elderly patients are diagnosed with MDS each year as well.
We know that long telomeres increase risk of cancer in cells.
Scientists found that cancer stem cells which have the enzyme called Telomeras, were found to be up to 15 times more active and may be the only cells responsible for cancer cell reproduction and metastasis. “We can now begin to think of cancer stem cells as being at the heart of tumour regrowth and turn our efforts away from ‘bulk cancer cells’, which don’t really drive tumour recurrence and metastasis.”
Now, we know how to aim at the cells responsible for tumor growth we can change how we fight cancer!
Puts a whole new spin on the Niki Lauda quote:
Stem cell ‘marking’ study offers alterative hypothesis of cancer metastasis
Date:January 18, 2017- Source: University of Salford – Summary: Stem cells are among the most energetically activated, migratory and proliferative sub-populations of tumour cells, according to observations by scholars at the Biomedical Research Centre at the University of Salford.
Cancerous stem cells are often left behind after chemotherapy with the potential to create new tumours — a process called recurrence and metastasis.
In research published in the journal Oncotarget, the Salford team conclude that stem cell characteristics and behaviour are instrumental in metastasis and believe the key to their reactivation is an enzyme called Telomerase, or hTERT.
Using lung, breast and ovarian cancer cells, the team set out to identify which cells are cancerous by their levels of Telomerase, an enzyme which endows cells with the ability to multiply.
To achieve this, they followed Telomerase activity with a fluorescent protein, GFP, more commonly found in jellyfish, effectively colouring each cells to mark it either ‘active’ or ‘inactive’.
Cells highlighted ‘fluorescent’ (hTERT-high) were found to be up to 15 times more active than others with an vastly increased capacity for migration and cell proliferation.
Michael Lisanti, Professor of Translational Medicine at the University of Salford said: “We reasoned that if we could spot the telomerase activity, we could identify which cells were cancerous.
“What we had not expected was to find the very rapid rate of proliferation of the cancer stem cells.
“Clearly, this contradicts the accepted view that stem cells do not proliferate quickly, and offers an alternative view of the process of metastasis, and moreover, a method of identifying, isolating and potentially killing tumour-forming cells.”
As part of the study, the team found that FDA-approved drugs, such as doxycycline and palbociclib, were effective at halting cancer stem cell propagation. Palbociclib blocks the activity of proteins known as cyclin-dependent kinases (CDK) and inhibits the division of cancer cells, but until now hadn’t been shown to effectively block cancer stem cell reproduction.
“The use of these FDA-approved drugs may provide a mechanism for treating metastatic disease on a larger scale and certainly opens the way for new Phase II clinical trials in multiple cancer types,” adds Professor Lisanti.
Dr Federica Sotgia, Reader of Translational Medicine at the University of Salford said: “We can now begin to think of cancer stem cells as being at the heart of tumour regrowth and turn our efforts away from ‘bulk cancer cells’, which don’t really drive tumour recurrence and metastasis.”
Gloria Bonuccelli, Maria Peiris-Pages, Bela Ozsvari, Ubaldo E. Martinez-Outschoorn, Federica Sotgia, Michael P. Lisanti. Targeting cancer stem cell propagation with palbociclib, a CDK4/6 inhibitor: Telomerase drives tumor cell heterogeneity. Oncotarget, 2016; DOI: 10.18632/oncotarget.14196
Scientists at The Scripps Research Institute (TSRI) have discovered a protein that fine-tunes the cellular clock involved in aging.
This novel protein, named TZAP, binds the ends of chromosomes and determines how long telomeres, the segments of DNA that protect chromosome ends, can be. Understanding telomere length is crucial because telomeres set the lifespan of cells in the body, dictating critical processes such as aging and the incidence of cancer.
“Telomeres represent the clock of a cell,” said TSRI Associate Professor Eros Lazzerini Denchi, corresponding author of the new study, published online today in the journal Science. “You are born with telomeres of a certain length, and every time a cell divides, it loses a little bit of the telomere. Once the telomere is too short, the cell cannot divide anymore.”
Naturally, researchers are curious whether lengthening telomeres could slow aging, and many scientists have looked into using a specialized enzyme called telomerase to “fine-tune” the biological clock. One drawback they’ve discovered is that unnaturally long telomeres are a risk factor in developing cancer.
“This cellular clock needs to be finely tuned to allow sufficient cell divisions to develop differentiated tissues and maintain renewable tissues in our body and, at the same time, to limit the proliferation of cancerous cells,” said Lazzerini Denchi.
In this new study, the researcher found that TZAP controls a process called telomere trimming, ensuring that telomeres do not become too long.
“This protein sets the upper limit of telomere length,” explained Lazzerini Denchi. “This allows cells to proliferate — but not too much.”
For the last few decades, the only proteins known to specifically bind telomeres is the telomerase enzyme and a protein complex known as the Shelterin complex. The discovery TZAP, which binds specifically to telomeres, was a surprise since many scientists in the field believed there were no additional proteins binding to telomeres.
“There is a protein complex that was found to localize specifically at chromosome ends, but since its discovery, no protein has been shown to specifically localize to telomeres,” said study first author Julia Su Zhou Li, a graduate student in the Lazzerini Denchi lab.
“This study opens up a lot of new and exciting questions,” said Lazzerini Denchi.
In addition to Lazzerini Denchi and Li, authors of the study, “TZAP: a telomere-associated protein involved in telomere length control,” were Tatevik Simavorian, Cristina Bartocci and Jill Tsai of TSRI; Javier Miralles Fuste of the Salk Institute for Biological Studies and the University of Gothenburg; and Jan Karlseder of the Salk Institute for Biological Studies.
The study was supported by the American Cancer Society (grant RSG-14-186-01), the Swedish Research Council International (grant D0730801) and the National Institutes of Health (grant R01GM087476 and R01CA174942).
Julia Su Zhou Li, Javier Miralles Fuste, Tatevik Simavorian, Cristina Bartocci, Jill Tsai, Jan Karlseder, Eros Lazzerini Denchi. TZAP: A telomere-associated protein involved in telomere length control. Science, 2017; DOI: 10.1126/science.aah6752
When white blood cells leave a vessel through the vessel wall, they contort their shape to pass through. But when stem cells exit a blood vessel, they don’t change their shape. They just pass on through the wall and the endothelial cells lining the vessel do the work by stretching around them and then actively expelling them. In other words, the stem cells are the Moses to the parting of the cells of the blood vessels:
“…when we looked at therapeutic stem cells… the endothelial cells not only changed their shape in order to surround the stem cell, they actually pushed the stem cells out of the blood vessel. We’ve named this process angiopellosis, and it represents an alternative way for cells to leave blood vessels.” Which begs the question…is this how cancer cells move around too?
Stem Cell Finding May Improve Understanding of Metastatic Cancers
A stem cell exits the bloodstream through angiopellosis. [Alice MacGregor Harvey, North Carolina State University]
Researchers at North Carolina State University have discovered that therapeutic stem cells exit the bloodstream in a different manner than was previously thought. This process, called angiopellosis by the researchers, has implications for improving our understanding of not only intravenous stem cell therapies, but also metastatic cancers.
When white blood cells need to get to the site of an infection, they can exit the bloodstream via a process known as diapedesis. In diapedesis, the white blood cell changes its shape to squeeze between or through the epithelial cells that form the walls of the blood vessel. Diapedesis is a well-understood process, and researchers believed that other types of cells, like therapeutic stem cells or even metastatic cancer cells, exited blood vessels in a similar way, with the cells pushing or squeezing themselves out.
But a group of researchers led by Ke Cheng, Ph.D., associate professor of molecular biomedical sciences at NC State with a joint appointment in the NC State/University of North Carolina (UNC)-Chapel Hill Department of Biomedical Engineering, found that these stem cells behaved differently. Their study (“Angiopellosis as an Alternative Mechanism of Cell Extravasation”) appears online in Stem Cells.
Therapeutic stem cells share the same ability to exit the bloodstream and target particular tissues that white blood cells do. But the precise way that they did so was not well understood, so Dr. Cheng and his team used a zebrafish model to study the process. The genetically modified zebrafish embryos were transparent and had fluorescently marked green blood vessels. Researchers injected the embryos with white blood cells and cardiac stem cells from humans, rats, and dogs. These cells had all been marked with a red fluorescent protein.
Through time-lapse, three-dimensional, light sheet microscopic imaging, Dr. Cheng and his team could trace the progress of these cells as they left the blood vessel. The white blood cells exited via diapedesis, as expected. When stem cells exited the blood vessel, however, the endothelial cells lining the vessel actively expelled them. Membranes surrounding the endothelial cells on either side of the stem cell stretched themselves around the stem cell, then met in the middle to push the stem cell out of the vessel.
“When you’re talking about diapedesis, the white blood cell is active because it changes its shape in order to exit. The endothelial cells in the blood vessel are passive,” Dr. Cheng says. “But when we looked at therapeutic stem cells, we found the opposite was true—the stem cells were passive—and the endothelial cells not only changed their shape in order to surround the stem cell, they actually pushed the stem cells out of the blood vessel. We’ve named this process angiopellosis, and it represents an alternative way for cells to leave blood vessels.”
The researchers found two other key differences between angiopellosis and diapedesis: one, that angiopellosis takes hours, rather than minutes, to occur and two, that angiopellosis allows more than one cell to exit at a time.
“Angiopellosis is really a group ticket for cells to get out of blood vessels,” notes Dr. Cheng. “We observed clusters of cells passing through in this way. Obviously, this leads us to questions about whether other types of cells, like metastatic cancer cells, may be using this more effective way to exit the bloodstream, and what we may need to do to stop them.”
“In contradiction to decades of medical education, a direct connection has been reported between the brain and the immune system….It seems astonishing that, after centuries of dissection, a system of lymphatic vessels could have survived undetected.”
EVERY time I have a conversation with someone who is 100% sure, I laugh inside and remember that everything we know for sure will be disproved within our lifetimes.
Medical science was 100% sure:
the heart doesn’t regenerate…wrong
the brain and central nervous system doesn’t regenerate…wrong
all of the ligaments have been found…wrong
butter is healthier, margarine is healthier, butter, margarine…wrong
stem cells don’t work…wrong
cholesterol is bad…wrong
and on and on and on and now…
This changes everything.
“It changes entirely the way we perceive the neuro-immune interaction,” says Kipnis. “We always perceived it before as something esoteric that can’t be studied. But now we can ask mechanistic questions.”
MS is known to be an example of the immune system attacking the brain, although the reasons are poorly understood. The opportunity to study lymphatic vessels that link the brain to the immune system could transform our understanding of how these attacks occur, and what could stop them. The causes of Alzheimer’s disease are even more controversial, but may also have immune system origins, and the authors suggest protein accumulation is a result of the vessels failing to do their job.
Indeed, Kipnis claims, “We believe that for every neurological disease that has an immune component to it, these vessels may play a major role.”
This changes everything.
Every single study dealing with brain and immune and GI systems must be revisited and re-evaluated.
For example, it begs the question…With so many people saying Autism is a neurological malfunction and so many people saying Autism is immune system caused and so many saying it is nutritional and heavy metal toxin caused…if these systems are all interconnected, perhaps they are all right. Is it time to reconsider the cause (causes!) of Autism?
What does it tell you when expert after expert tries to discredit the results of Gordie Howe’s stem cell treatment while his son Dr. Murray Howe, chairman of Toledo Hospital’s department of radiology, credits the stem cells for his recovery?
Dr. Murray Howe is the chairman of Toledo Hospital’s department of radiology.
What does it tell you when expert after expert claim his recovery and improvements are insignificant…while simultaneously attributing his recovery and improvements to everything except the stem cells he received?
What does it tell you when expert after expert discredits the anecdotal evidence of Gordie Howe’s recovery as “merely anecdotal” while it is actually one mere drop in an ocean of tens of thousands per year who have improved from cancer with cellular therapies over the last 59 years and tens of thousands who have improved over the past 12-14 years from non-cancer conditions?
And what is the value of this huge array of empirical and anecdotal evidence?
Gordie Howe Recovers From Stroke with Stem Cells
There are many types of evidence, not just trials or anecdotal. Too often we reduce the evidential options to either clinical trials or anecdote. Wrong. That’s 5 blind men describing an elephant all over again. We must take into account ALL of the different types of evidence and only THEN we can make a judgment based on the cumulative evidential data.
Anecdotal Evidence – Peyton Manning, Kobe Bryant, Rafael Nadar, Bartolo Colon…athletes from major sports organizations all over the world are embracing and anecdotally illustrating the safety and efficacy of cellular therapies
Statistical Evidence – 50,000 patients per year… are statistically illustrating the safety and efficacy of cellular therapies
Testimonial Evidence – Youtube is chock full of testimonies of athletes and patients who are benefiting from cellular therapies and via testimonial, illustrating the safety and efficacy of cellular therapies
Analogical Evidence – 59 years and thousands of trials and studies are analogously illustrating the safety and efficacy of cellular therapies
Clinical Trial evidence – Even though it may be the wrong process to evaluate cellular therapies, the vast majority of over 2,400 clinical trials are scientifically and empirically illustrating the safety and efficacy of cellular therapies
Miracle results? No. This is par for the course results from real expectations based on the multitude of evidence types collected over the past six decades for cellular therapies. The combined patchwork of all of the data from all of these evidences paints a very compelling conclusion.
Are cellular therapies safe and effective? All of the evidences seem to say so. Not just the anecdotal evidence;
and clinical trial evidences.
1. Last week I saw someone with no education on stem cells stating that stem cells should be used only as a last resort.
The presentation of stem cell therapies as a last resort is tragic. Unfortunately, most people do come to me asking for information as a last resort. They have been advised by their friends, family, medical professionals and media that they should try everything else and not try stem cells. When all else fails and they finally approach me, “I’ve tried everything,” is a common explanation. Again, tragic. In many cases, the sooner stem cells are used, the faster patients can improve their quality of life, relieve their suffering and mediate their symptoms.
The CEO of a well known stem cell company made this analogy: “Most people renovate their homes just before selling them. What a missed opportunity! If they renovated them earlier they would derive years of pleasure from the renovation instead of fixing things up for the next owner.” But what if you used stem cell therapies to improve your health and fix your body BEFORE you exhausted all other resources, money, energy, your immune system and your health? What a concept.
2. A new study is investigating the question: Is stem cell therapy less effective in older patients with chronic diseases?
When was the last time a piece of equipment in your car failed and another one didn’t fail soon after. This is because they are dependent upon each other for optimum efficiency. The older the patient and the more advanced their disease, the odds are, the more there are other organs and systems being taxed beyond their capabilities. And many people believe one pill will fix their disease but it’s far from true. We must change the one pill for one one disease, one size fits all, magic cure belief which is rampant in the USA. There is no evidence to support it.
Look at it another way. Consider your body a battleground and the disease is the enemy. The surest way to fight the enemy is to send wave after wave of soldiers (stem cells) into battle. But many of the same issues in battle restrict maximizing the success of your therapy. If you cut off the supply routes to the soldiers carrying food and ammunition (a weakened or restricted circulatory system), your soldiers’ ability to move to the battle will be ineffective. If you wipe out their communications (cytokines/messenger cells), your soldiers won’t know where to go or what is needed to fight.
Time is always against us. The longer we wait, the more our resources will be depleted and our other organs and systems will be taxed, both to support the failing areas and due to the natural deterioration associated with aging. “Aging and chronic diseases including CVD and diabetes substantially affect stem/progenitor cells of adult organism. Such conditions could restrict the effectiveness of autologous cell therapy in aged patients with CAD, lower limb ischemia, T2DM and other chronic pathologies, although these patients are some of the most obvious candidates for cell therapy.”
It is my hope that people do real research or talk to someone who has so they can make an educated decision about reclaiming their health. There is a great deal of misinformation out there and many people are trying to sabotage the real info and data getting to those whom need it most. Let’s work together to get rid of misinformation and not perpetuate the confusion which may lead to unnecessary suffering. DON’T WAIT.
Adult Stem Cell Therapy Awareness
Adult Stem Cell Therapy – Raising Awareness of Medical Advancements Source: adultstemcelltherapy… A Guide to the Healing Potential of an Innovative & Promising Treatment of Dreaded Diseases.