Motion is Lotion

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Imagine waking up one morning with a frozen shoulder where you couldn't move your upper arm more than a few inches in any direction. How much would that impact your ability to do your job? How much would that affect your ability to drive your car or even to dress yourself? How much would that affect your ability to concentrate on anything other than your shoulder? Obviously, if your shoulder did not move correctly, it would have a dramatic impact on your life. Well, the same is true with movement in every part of your body. If things aren't moving the way they are supposed to move, it will have a negative impact on your ability to function at work, take care of the demands of everyday life, and even your ability to concentrate.

Many patients with severe low back pain report that their pain came on suddenly when they did something as simple as bend down to pet their cat, put on their socks, or pick up the newspaper. Just about everyone would agree that a person's body should be able to handle such simple movements. So what has happened?

In every one of these cases, the joints of the patient's body were "all locked up" -- they were barely moving at all. When the joints in one area of the body do not move the way they should, other areas of the body are forced to move more in order to compensate. This creates a significant stress on those areas that have to pick up the slack, and it soon leads to pain and inflammation. At the same time, the areas that don't have normal movement will slowly worsen as the muscles continue to tighten, the joints stick together, and the ligaments and tendons shorten. This leaves the body in a very unstable condition; if left unchecked, this process will continue until the body can hardly move at all. That is how a person comes to suffer flare-ups of pain at the slightest provocation.

Most of us have seen people who have lost most of their normal mobility: they look like bodies have been starched stiff whenever they try to move around. This is especially prevalent among the elderly. Contrary to popular belief, however, this is not an inevitable effect of aging; rather it is the inevitable effect of not maintaining the body's mobility through exercise, healthy alignment, and body mechanics. There are people in their 60s, 70s, or even older, who are stronger and more flexible than the average person in their 30s, simply because they keep themselves exercising.

Maintaining mobility is critical in order to live free from pain and disability. Maintaining good mobility is not difficult, but it does not happen on its own. Just as in developing a good posture, it is necessary that you perform specific exercises and stretches to keep your muscles, ligaments, and tendons flexible and healthy. In addition, it is necessary that all of the joints in your body are kept moving correctly as well. Although this can be achieved to a great degree through stretching, most people also find routine chiropractic adjustments to be very beneficial.

FOODS FOR JOINT PAIN

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Can your diet affect joint pain?

Joint pain may be experienced as a result of an acute injury, such as an ankle sprain, knee sprain, or rotator cuff tear. Joint pain may also accompany varying types of joint inflammation, including osteoarthritis (degenerative joint disease), rheumatoid arthritis, psoriatic arthritis, and joint inflammation secondary to lupus erythematosus and irritable bowel syndrome. Of the numerous causes of joint inflammation, osteoarthritis is by far the most common, frequently affecting the lower back, neck, hips, knees, shoulders, and wrists. Many factors are associated with the development of osteoarthritis, including overuse, too little use, faulty biomechanics, and overall lack of exercise. Joint pain related to osteoarthritis may be improved and ameliorated to a certain extent by engaging in a comprehensive program of restoring more efficient biomechanics, targeted exercise, and healthy nutrition.

Diet is frequently implicated in various systemic inflammatory disorders and, in consequence, various joint inflammatory conditions. For example, celiac disease, a chronic inflammatory disorder, is often associated with gluten insensitivity or gluten intolerance. Malabsorption syndrome and leaky gut syndrome, both of which may be associated with joint inflammation, may be associated with gluten insensitivity or gluten intolerance. The inclusion of nutritional supplementation such as probiotics and prebiotics is helpful in the overall management of malabsorption syndrome and leaky gut syndrome. As well, instituting a gluten-free diet may be of assistance in managing gluten sensitivity, gluten intolerance, and conditions such as celiac disease.

Additionally, sugar, refined carbohydrates, saturated fats, monosodium glutamate, and alcohol are known causes and potentiators of joint inflammation. For certain individuals, dairy products, eggs, tomatoes, nuts, and coffee may exacerbate existing joint inflammation. In contrast, for most people, diets containing at least five servings of fresh fruits and vegetables daily help prevent the development of joint inflammation and help reduce inflammatory processes and thus ameliorate a primary cause of joint pain.

Exercise helps to improve joint range of motion, strengthen supporting muscle groups, and increase the resiliency and flexibility of local soft tissues such as tendons and ligaments. Optimally, exercise is done five days a week for at least 30 minutes each day. Beneficial forms of exercise include walking, swimming, bicycling, yoga, and strength training. If you haven't exercised in some time, start slowly and gently, building up your capacity and stamina.

Regular chiropractic care plays a key role in the effective management of joint pain. By detecting and correcting sources of spinal nerve irritation and nerve interference, regular chiropractic care helps to optimize the functioning of your entire physiology. Potential causes of joint pain in the neck, mid back, and lower back are addressed directly, and joint pain in other locations is benefited by more normalized communication between those sites and the nerve system as a whole. In this way, regular chiropractic care helps improve the long-term overall health and well-being of you and your family.

Basu A et al: Dietary fruits and arthritis. Food Funct 9(1):70-77, 2018

Oliviero F, et al: Anti-inflammatory effects of polyphenols in arthritis. J Sci Food Agric 98(5):1653-1659, 2018

Aryaeian N, et al: The effect of ginger supplementation on some immunity and inflammation intermediate genes expression in patients with active rheumatoid arthritis. Gene 698:179-185, 2019

What's the problem with Big-Pharma getting involved with stem cell therapy?

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Would you pay $500,000 for a one-time stem cell treatment? You would if it was your little girl that had cancer, and Big-Pharma knows it.

Yes, if your child were to get leukemia there is a stem cell treatment named Kymriah by Novartis Pharmaceuticals that will charge you $500,000 dollars for a one time treatment. Yes, a half million dollars! it appears to be about 85% effective but that's a little steep for anyone’s budget. Within the next year those costs are expected to come down to about $300,000 for a single dose. What a bargain!

My concern with Stem Cell Therapy and Big-Pharma? The FDA will likely continue to provide pathways for approval primarily favoring pharmaceutical companies with deep pockets and FDA privileges that exceed smaller companies such as ours. In this way the FDA will continue to call YOUR stem cells a drug and therefore require pathways exactly the same as drug manufacturing - costing companies between 1.5 - 2.0 billion dollars to get approval (the average costs from inception to drug approval in the U.S. is $2,000,000,000.00 - not a misprint!), and when that’s the requirement you get stem cell therapies that cost a half-million dollars.

The FDA needs only to provide strict guidelines to be followed by physicians, such as sterile technique and proof of good manufacturing practices (GMP). Then let the market determine stem cell price points. Otherwise, leaving the country will continue to be a normal thing for medical treatments.

Don't get a steroid shot in your knee! Here's why...

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Below details the result of a study looking at repeated steroid shots for knee pain - The conclusion? It will wear out your knee faster than if you just left it alone. Repeated steroid injections only furthers the likelihood that you’ll need a much more invasive procedure later.

Better yet… Stem Cell injections into the knee can repair the knee and avoid knee surgery all-together :)

Osteoarthritis Cartilage. 2019 Jan 29. pii: S1063-4584(19)30033-0. doi: 10.1016/j.joca.2019.01.007. [Epub ahead of print]

Intra-articular corticosteroids and the risk of knee osteoarthritis progression: results from the Osteoarthritis Initiative.

Zeng C1, Lane NE2, Hunter DJ3, Wei J4, Choi HK5, McAlindon TE6, Li H7, Lu N8, Lei G9, Zhang Y10.

Author information

Abstract

OBJECTIVE:

A recent randomized clinical trial reported that repeated intra-articular corticosteroids (IACs) were associated with a greater cartilage loss. This study aimed to examine the relation of IACs to knee radiographic osteoarthritis (ROA) progression in a real-world setting.

DESIGN:

A cohort that initiated IACs and a comparison cohort without IACs from participants with mild to moderate knee ROA in the Osteoarthritis Initiative (OAI) were assembled (from 0-month to 48-month). Two measures of knee ROA progression were assessed during the follow-up period: (1) an increase in Kellgren and Lawrence (KL) grade by ≥1 grade or having a knee replacement (i.e., KL grade worsening); and (2) a decrease in joint space width (JSW) by ≥0.7 mm or having a knee replacement (i.e., JSW worsening). The associations of IACs initiation using a propensity-score matched cohort study and continuous IACs using marginal structural models with the risk of knee ROA progression were examined.

RESULTS:

Among 684 propensity-score matched participants at baseline (148 IACs initiators, 536 comparators), 65 knees (21.7/100 person-years) in the IACs initiation cohort and 90 knees (7.1/100 person-years) in the comparison cohort experienced KL worsening. The hazard ratios (HRs) of KL worsening from IACs initiation and continuous IACs were 3.02 (95% confidence interval [CI], 2.19-4.16) and 4.67 (95% CI, 2.92-7.47), respectively. The corresponding HRs of JSW worsening were 2.93 (95% CI, 2.13-4.02) and 3.26 (95% CI, 1.78-5.96), respectively. All HRs for continuous use of IACs were further away from the null.

CONCLUSIONS:

IACs, especially continuous IACs, may be associated with an increased risk of knee ROA progression.

Copyright © 2019 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

KEYWORDS:

Cohort; Corticosteroids; Osteoarthritis; Progression

PMID: 30703543 DOI: 10.1016/j.joca.2019.01.007

Have we found the answer to MS? - Stem Cells

https://cbsloc.al/2QUy0w6?anvt=60

Multiple Sclerosis is a devastating auto-immune disease that can disable and cripple millions of Americans every year. In 75% of the cases, it is the remitting and relapsing type. In this form of MS, it is extremely frustrating for the patients as they never know what function of their body it is going to effect next, anything from loss of vision to loss of the ability to walk and it’s completely random.

Recently more and more research is pointing to the stem cell therapy as being the closest thing to a cure. In this video link above you’ll see an account of two women who responded well and off all MS medications.

At our office we are also conducting case studies to learn the effects of stem cell therapy on a number of different auto-immune conditions such as MS.

Call today and lets discuss your specific condition and see if you might be a good candidate for our program.

-Dr Bean

Stem Cell Therapy Shown Effective For Lupus

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A New POC (Proof Of Concept) Study Shows Positive Results and Supports Further Investigation into Stem Cell Research for Lupus

Stem cell therapy is one of the most promising frontiers in lupus research today. A proof of concept (POC) study from Spain captured results using mesenchymal stem cells (MSCs) to treat lupus nephritis. MSCs are unique adult stem cells with immunosuppressive properties that also may play a key role in preventing autoimmunity. The MSCs in this study were transplanted into a small subset of people (3) with lupus nephritis and each responded favorably to this early treatment. Although very small, the study outcomes provide ongoing support for MSC research in lupus.

A POC study can be used to gather preliminary data about the drugs mechanism of action and help support further research in humans. The three patients in this study all received MSCs and were followed for 9 months after infusion. All three patients responded to therapy, with two patients considered to be complete responders (meaning they met all the endpoints in the protocol). This study was significant because it showed that MSC treatment for lupus nephritis was effective for patients from varying ethnic backgrounds. A larger phase 2 study to test the safety and efficacy for MSCs in lupus nephritis is currently enrolling in Spain.

The Lupus Foundation of America has a long history of funding (adult) stem cell research. The Foundation was one of the first private funders of research into MSCs as a potential treatment for people with lupus. Currently, in partnership with the National Institute of Allergy and Infectious Diseases, the Foundation has co-funded a major study of MSCs as a new treatment for moderate to severe lupus. This innovative study is led by Gary Gilkeson, M.D., and Diane Kamen, M.D., of the Medical University of South Carolina (MUSC) and marks a bold step forward in lupus research, which has only had one drug that was specifically developed for lupus and approved by the U.S. Food and Drug Administration (FDA). The phase II trial is underway with seven academic centers participating in the research. Continue to follow LFA for updates on MSCs. Learn more about the Foundation's stem cell research.

-Lupus Foundation of America

Fortunately, we have the means and providers available to make this a reality. We are currently studying the effects stem cell therapy for Lupus. Please call 801-327-9336

-Dr Bean

Copy of Consumer Reports: New, unproven stem cell treatment danger

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It is true. There are risks with stem cell treatments. Mostly concerns of infection from a tainted product received from biotech companies or offices poorly prepared or simply irresponsible when it comes to sterile technique.

When dealing with stem cell clinics who utilize the patients own cells, the risks go down. There’s no chance of rejection, as these are your cells and not mixed with any other individuals cells. However, even in the best of circumstances infection is still a risk. How many people have you met who had a total knee or hip replacement that got infected? Happen’s all the time, right? It’s real problem even in hospital settings.

As a group we have decided to use protocols developed by the Cell Surgical Network. These protocols for studying cell therapy have been submitted to the FDA as an IRB (Institutional Review Board). This is not the same as an IND (Investigational New Drug). Any organization wanting to study a new drug or cell therapy as we are, has to go through the steps for approval. An IRB is simply a much less costly way of collecting data on our procedures for the FDA to see with transparency. They are then able to see what we are doing and what results we are seeing in our population of patients undergoing these treatments. Therefore an IRB is a more likely scenario for smaller organizations like ours that do not have millions if not billions in its coffers to dispose of readily on clinical trials. Sadly, the costs associated to approve a new drug such as the case with an IND, precludes many wonderful and successful therapies to ever see the light of day.

Be Aware: There are many offices throughout the US that are pushing stem cell therapy. Just do a google search for stem cell treatments and you’ll get inundated with advertisements from physician, chiropractic, naturopathic and oriental medicine clinics located all across the globe. Why? Well… first of all because it is effective with very low risk of side effects or injury. Who wouldn’t rather regenerate their own tissues in the body then try to replace or repair them with techniques and parts that often fail, get infected, require down time, don’t work right, still hurt and very, very expensive. The average knee replacement in the US is $57,000. The average stem cell injection is $10,000. It just makes sense every way you look at it.

In this Consumer Report article they expand on these concerns of unproven stem cell injections and the potential risks. The E coli outbreak was because of an infected lot associated with donated umbilical cord tissues. Again, this is a quality control issue with the biotech company that produced this product, not the individual offices that were using the tainted product.

As with any new product, buyer be ware. Do your homework. Investigate. Ask questions. Get references. Ultimately, you need to get to a point where you feel 100% comfortable with the group you’re working with.

-Dr Bean

Consumer Reports: New, unproven stem cell treatment danger

stem-cell-junky.jpg

It is true. There are risks with stem cell treatments. Mostly concerns of infection from a tainted product received from biotech companies or offices poorly prepared or simply irresponsible when it comes to sterile technique.

When dealing with stem cell clinics who utilize the patients own cells, the risks go down. There’s no chance of rejection, as these are your cells and not mixed with any other individuals cells. However, even in the best of circumstances infection is still a risk. How many people have you met who had a total knee or hip replacement that got infected? Happen’s all the time, right? It’s real problem even in hospital settings.

As a group we have decided to use protocols developed by the Cell Surgical Network. These protocols for studying cell therapy have been submitted to the FDA as an IRB (Institutional Review Board). This is not the same as an IND (Investigational New Drug). Any organization wanting to study a new drug or cell therapy as we are, has to go through the steps for approval. An IRB is simply a much less costly way of collecting data on our procedures for the FDA to see with transparency. They are then able to see what we are doing and what results we are seeing in our population of patients undergoing these treatments. Therefore an IRB is a more likely scenario for smaller organizations like ours that do not have millions if not billions in its coffers to dispose of readily on clinical trials. Sadly, the costs associated to approve a new drug such as the case with an IND, precludes many wonderful and successful therapies to ever see the light of day.

Be Aware: There are many offices throughout the US that are pushing stem cell therapy. Just do a google search for stem cell treatments and you’ll get inundated with advertisements from physician, chiropractic, naturopathic and oriental medicine clinics located all across the globe. Why? Well… first of all because it is effective with very low risk of side effects or injury. Who wouldn’t rather regenerate their own tissues in the body then try to replace or repair them with techniques and parts that often fail, get infected, require down time, don’t work right, still hurt and very, very expensive. The average knee replacement in the US is $57,000. The average stem cell injection is $10,000. It just makes sense every way you look at it.

In this Consumer Report article they expand on these concerns of unproven stem cell injections and the potential risks. The E coli outbreak was because of an infected lot associated with donated umbilical cord tissues. Again, this is a quality control issue with the biotech company that produced this product, not the individual offices that were using the tainted product.

As with any new product, buyer be ware. Do your homework. Investigate. Ask questions. Get references. Ultimately, you need to get to a point where you feel 100% comfortable with the group you’re working with.

-Dr Bean

Dissecting 4 possible roles for stem cell therapy besides cell replacement by stem cell scientist Paul Knoepfler

Dissecting 4 possible roles for stem cell therapy besides cell replacement

February 6, 2019 Paul Knoepfler anti-agingexosomesGrowth factorssenolyticsstem cellsstem cells aging 3

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An illustration of stem cell drug delivery by Taylor Seamount Stem Cells: An Insider’s Guide by Paul Knoepfler.

Historically, the main route of proposed healing via stem cells was cell replacement. In this way of thinking the transplanted cells engrafted (took up home) in the patient’s tissue and replaced dead or diseased cells. However, interest continues to grow in other possible modes of healing by stem cells that don’t rely on cell replacement. In today’s post I cover 4 other possible mechanisms.

Secreted factors

An alternative, not mutually exclusive model to cell replacement is that stem cell transplants have beneficial effects via the factors they directly secrete. These growth factors, cytokines, and other molecules (collectively sometimes called “the secretome”) could have a positive impact by a number of mechanisms. After stem cell transplantation, these factors might tell endogenous stem or precursor cells to start growing. They could tell some cells not to die, while encouraging others that are beyond hope and might actually be mediating toxic effects to go ahead and croak. (Incidentally, you might have seen the research (mentioned here) supporting the notion that senescent cells hanging around the body are actually actively harmful and removing them could fight aging. There’s even a germinal field of “senolytics”.) Secreted molecules might also stimulate angiogenesis, aiding in tissue healing. It’s a fact of life that secreted factors produced by transplanted stem cells would also pose risks such as sparking cancer or enhancing the growth of an already existing, undetected tumor.

Immunosuppression

Another popular, related idea is that infused stem cell specifically have immunosuppressive functions. In this way of thinking, although injected stem cells don’t stay around a long time, while present they tell the immune system to “cool it”. It’s an interesting concept, but not concretely proven. Let’s say for the moment that it sometimes happens. In that context, we have to be very aware of risks associated with this hypothetical stem cell-mediated immunosuppression. For instance, patients may get sick from an infection or developing a tumor as a consequence of reduced immune activity. The immunosuppressive route of function has been discussed the most for mesenchymal stem cells or whatever you prefer the MSC acronym to stand for these days.

Exosomes

An additional idea invokes a different kind of “secretion” by cells. In addition to making molecules that are dumped out directly into the interstitial space, the blood, or onto neighboring cells, stem cells (and really all cells) make what are called exosomes. These are little, budded-off membrane-bound packages full of many different molecules. Exosomes can then deliver their soup of factors to other cells. There is a lot of legitimate excitement about exosomes and their possible clinical potential. Unfortunately, there is abundant hype too. Also, some unproven “exosome therapy” is already being sold to patients. Of course, if exosomes can have potential benefits, their function as little packages of potent molecules will also pose some risks, which at this point are not well understood.

Drug delivery

This last notion is related to the first three ideas above, but involves more time in the lab. Stem cells can be engineered in the lab to produce (or be loaded with) drugs that they then can secrete or in theory deliver with exosomes or even by cell fusion. In this way designer stem cells, once transplanted, can potentially deliver medicines to a diseased tissue. This delivery could even be on a cell-to-cell basis (I could say one cell acts as doctor and the other as patient, but I won’t), rather than systemically as most pharmaceutical drugs are given. For example, imagine stem cells loaded with chemotherapy delivering it directly to a brain tumor like a glioma.

Risks here include that the stem cells give too much drug, that the drug is delivered to the wrong cells, that the drug given by stem cells is uniquely toxic, or that the designer stem cells themselves engraft and grow into an undesired tissue or have some other negative effects. That last possibility is perhaps avoidable via a built in cellular suicide switch.

You can see an illustration of envisioned stem cell-based drug delivery to a diseased region of brain in an illustration by Taylor Seamount for my book, Stem Cells: An Insider’s Guide, above.

Overall, what other possible, helpful non-cell replacement-based roles for transplanted stem cells come to mind?

Credit to Paul Knoepfler for this article.

Targeting senescent cells for apoptosis extends life... fountain of youth?

Senolytics improve health, extend life: Preclinical research findings

July 9, 2018

ROCHESTER, Minn. — The presence of senescent or dysfunctional cells can make young mice age faster. And using senolytic drugs in elderly mice to remove these rogue cells can improve health and extend life. These findings from Mayo Clinic researchers and collaborators provide a foundation on which to move forward in this area of aging research. The results appear in Nature Medicine.

“We can say with certainty that senescent cells can cause health problems in young mice, including causing physical dysfunction and lowering survival rates, and that the use of senolytics can significantly improve both health span and life span in much older naturally aged animals,” says James Kirkland, M.D., Ph.D., a Mayo Clinic geriatrics researcher who heads Mayo Clinic’s Kogod Center on Aging. Dr. Kirkland is senior author of the study.

The first senolytic drugs —compounds that remove senescent cells from the body — were discovered at Mayo Clinic. The senolytics used in this study are a cocktail of dasatinib, which promotes cancer cell death, and quercetin, an antioxidant found in apples and other foods. In effect, senolytics act by allowing senescent cells to “self-destruct” rather than damage healthy cells nearby and throughout the rest of the body.

How the study was performed

The researchers transplanted senescent cells into young mice and a group of middle-aged mice that had aged naturally. Transplanting even small numbers of senescent cells was sufficient to cause the mice to become frail and reduce their survival. Fewer senescent cells were needed to cause these effects in older mice than younger mice or in high fat-fed than in lean mice. This means that obesity worsens the effects of aging. Problems were prevented or reversed in the mice transplanted with senescent cells by treating these mice with senolytics.

In naturally aged mice, roughly equivalent to 80 human years, administering the senolytic cocktail orally improved physical function. The mice were better able to run on a treadmill and maintain a stronger grip strength, and they had increased daily activity. Remaining life span was extended by 36 percent, compared to the norm for this strain of mice. And the increase in life span did not come at the cost of a prolonged period of frailty near the end of life. Death from age-related diseases as a group was delayed and was generally due to old age rather than any single age-related disease, such as cancer. Furthermore, the senolytics killed human senescent cells within 48 hours in fat samples taken directly from the operating room.

Translating to humans

The researchers caution these senolytic agents should not be taken by people, unless their safety and effectiveness is demonstrated in clinical trials. They say if these agents turn out to be effective and safe in such clinical trials, senolytics could help alleviate physical dysfunction and frailty in older people, while increasing independence in later life.

Collaborators on the study are from Newcastle University, Newcastle upon Tyne, U.K.; Indiana University Bloomington, Bloomington, Indiana; The University of Alabama at Birmingham, Birmingham, Alabama; The University of Texas Health Science Center at San Antonio, San Antonio, Texas; South Texas Veterans Health Care System, San Antonio; The Scripps Research Institute, Jupiter, Florida; and the University of Connecticut Center on Aging, UConn Health, Farmington, Connecticut.

The research was supported by multiple grants from the National Institutes of Health, as well as the Connor Group, Robert J. and Theresa W. Ryan, the Glenn/American Federation for Aging Research, the Ted Nash Long Life and Noaber Foundations, and Robert and Arlene Kogod. Some of the researchers have a financial interest in the outcomes of this research, and Mayo Clinic has patents on senolytic drugs. Details and full author list appear on the paper.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to clinical practice, education and research, providing expert, comprehensive care to everyone who needs healing. Learn more about Mayo ClinicVisit the Mayo Clinic News Network.

Why "fat" is the future of regenerative medicine

Stanford University decade long study identifies stem cell that gives rise to new bone, cartilage in humans. hint - it’s found in FAT

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Identification of the human skeletal stem cell by Stanford scientists could pave the way for regenerative treatments for bone fractures, arthritis and joint injuries.

SEP 202018

A decade-long effort led by Stanford University School of Medicine scientists has been rewarded with the identification of the human skeletal stem cell.

The cell, which can be isolated from human bone or generated from specialized cells in fat, gives rise to progenitor cells that can make new bone, the spongy stroma of the bone’s interior and the cartilage that helps our knees and other joints function smoothly and painlessly.

The discovery allowed the researchers to create a kind of family tree of stem cells important to the development and maintenance of the human skeleton. It could also pave the way to treatments for regenerating bone and cartilage in people.

“Every day, children and adults need normal bone, cartilage and stromal tissue,” said Michael Longaker, MD, professor of plastic and reconstructive surgery. “There are 75 million Americans with arthritis, for example. Imagine if we could turn readily available fat cells from liposuction into stem cells that could be injected into their joints to make new cartilage, or if we could stimulate the formation of new bone to repair fractures in older people.”

A paper describing the finding, which follows the discovery by the same group of the mouse skeletal stem cell in 2015, was published online Sept. 20 in Cell.

Longaker, the Deane P. and Louise Mitchell Professor in the School of Medicine and the co-director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine, is the senior author. The lead authors are Charles K.F. Chan, PhD, assistant professor of surgery; medical student Gunsagar Gulati, MD; Rahul Sinha, PhD, instructor of stem cell biology and regenerative medicine; and research assistant Justin Vincent Tompkins.

‘True, multipotential, self-renewing’

The skeletal stem cells are distinct from another cell type called the mesenchymal stem cell, which can generate skeletal tissues, fat and muscle. Mesenchymal stem cells, which can be isolated from blood, bone marrow or fat, are considered by some clinicians to function as all-purpose stem cells. They have been tested, with limited success, in clinical trials and as unproven experimental treatments for their ability to regenerate a variety of tissues. Recently, three elderly patients in Florida were blinded or lost most of their sight after mesenchymal stem cells from fat were injected into their eyes as an experimental treatment for macular degeneration.

“Mesenchymal stem cells are loosely characterized and likely to include many populations of cells, each of which may respond differently and unpredictably to differentiation signals,” Chan said. “In contrast, the skeletal stem cell we’ve identified possesses all of the hallmark qualities of true, multipotential, self-renewing, tissue-specific stem cells. They are restricted in terms of their fate potential to just skeletal tissues, which is likely to make them much more clinically useful.”

Skeletal regeneration is an important capability for any bony animal evolving in a rough-and-tumble world where only the most fit, or the fastest-healing, are likely to survive very long into adulthood. Some vertebrates, such as newts, are able to regenerate entire limbs if necessary, but the healing ability of other animals, such as mice and humans, is more modest. Although humans can usually heal a bone fracture fairly well, they begin to lose some of that ability with age. And they are completely unable to regenerate the cartilage that wears away with age or repetitive use. Researchers have wondered whether the skeletal stem cell could be used clinically to help replace damaged or missing bone or cartilage, but it’s been very difficult to identify.

Adult stem cells lineage-restricted

Unlike embryonic stem cells, which are present only in the earliest stages of development, adult stem cells are thought to be found in all major tissue types, where they bide their time until needed to repair damage or trauma. Each adult stem cell is lineage-restricted — that is, it makes progenitor cells that give rise only to the types of cells that naturally occur in that tissue. For our skeleton, that means cells that make bone, cartilage and stroma.

Michael Longaker

Chan, Longaker and their colleagues had hoped to use what they learned from identifying the mouse skeletal stem cell to quickly isolate its human counterpart. But the quest turned out to be more difficult than they had anticipated. Most cell isolation efforts focus on using a technology called fluorescence activated cell sorting to separate cells based on the expression of proteins on their surface. Often, similar cell types from different species share some key cell surface markers.

But the human skeletal stem cell turned out to share few markers with its mouse counterpart. Instead, the researchers had to compare the gene expression profiles of the mouse skeletal stem cell with those of several human cell types found at the growing ends of developing human bone. Doing so, they were able to identify a cell population that made many of the same proteins as the mouse skeletal stem cell. They then worked backward to identify markers on the surface of the human cells that could be used to isolate and study them as a pure population.

“This was quite a bioinformatics challenge, and it required a big team of interdisciplinary researchers, but eventually Chuck and his colleagues were able to identify a series of markers that we felt had great potential,” Longaker said. “Then they had to prove two things: Can these cells self-renew, or make more of themselves indefinitely, and can they make the three main lineages that comprise the human skeleton?”

The researchers showed that the human skeletal stem cell they identified is both self-renewing and capable of making bone, cartilage and stroma progenitors. It is found at the end of developing bone, as well as in increased numbers near the site of healing fractures. Not only can it be isolated from fracture sites, it can also be generated by reprogramming human fat cells or induced pluripotent stem cells to assume a skeletal fate.

‘The perfect niche’

Intriguingly, the skeletal stem cell also provided a nurturing environment for the growth of human hematopoietic stem cells — or the cells in our bone marrow that give rise to our blood and immune system — without the need for additional growth factors found in serum.

“Blood-forming stem cells love the interior of spongy bone,” Chan said. “It’s the perfect niche for them. We found that the stromal population that arises from the skeletal stem cell can keep hematopoietic stem cells alive for two weeks without serum.”

By studying the differentiation potential of the human skeletal stem cell, the researchers were able to construct a family tree of stem cells to serve as a foundation for further studies into potential clinical applications. Understanding the similarities and differences between the mouse and human skeletal stem cell may also unravel mysteries about skeletal formation and intrinsic properties that differentiate mouse and human skeletons.

The skeletal stem cell we’ve identified possesses all of the hallmark qualities of true, multipotential, self-renewing, tissue-specific stem cells. 

“Now we can begin to understand why human bone is denser than that of mice, or why human bones grow to be so much larger,” Longaker said.

In particular, the researchers found that the human skeletal stem cell expresses genes active in the Wnt signaling pathway known to modulate bone formation, whereas the mouse skeletal stem cell does not.  

The ultimate goal of the researchers, however, is to find a way to use the human skeletal stem cell in the clinic. Longaker envisions a future in which arthroscopy — a minimally invasive procedure in which a tiny camera or surgical instruments, or both, are inserted into a joint to visualize and treat damaged cartilage — could include the injection of a skeletal stem cell specifically restricted to generate new cartilage, for example.

“I would hope that, within the next decade or so, this cell source will be a game-changer in the field of arthroscopic and regenerative medicine,” Longaker said. “The United States has a rapidly aging population that undergoes almost 2 million joint replacements each year. If we can use this stem cell for relatively noninvasive therapies, it could be a dream come true.”

Longaker is a member of the Stanford Child Health Research Institute, the Stanford Cardiovascular Institute, the Stanford Cancer Institute and Stanford Bio-X.

Additional Stanford authors are CIRM Scholars Michael Lopez, Rachel Brewer, and Lauren Koepke, former graduate students Ava Carter, PhD, Ryan Ransom, graduate students Anoop Manjunath, and Stephanie Conley; former postdoctoral scholar Andreas Reinisch, MD, PhD; research assistant Taylor Wearda; clinical assistant professor of plastic and reconstructive surgery Matthew Murphy, MD; medical student Owen Marecic; former life sciences researcher Eun Young Seo; former research assistant Tripp Leavitt, MD; research assistants Allison Nguyen, Ankit Salhotra, Taylor Siebel, and Karen M Chan; instructor of stem cell biology and regenerative medicine Wan-Jin Lu, PhD; postdoctoral scholars Thomas Ambrosi, PhD, and Mimi Borrelli, MD; orthopaedic surgery resident Henry Goodnough, MD, PhD; assistant professor of orthopaedic surgery Julius Bishop, MD; professor of orthopaedic surgery Michael Gardner, MD; professor of medicine Ravindra Majeti, MD, PhD; associate professor of surgery Derrick Wan, MD; professor of surgery Stuart Goodman, MD, PhD; professor of pathology and of developmental biology Irving Weissman, MD; and professor of dermatology and of genetics Howard Chang, MD, PhD.

Researchers from the Medical University of Graz in Austria, RIKEN in Japan and the University of California-San Diego also participated in the study.

The study was supported by the National Institutes of Health (grants R01DE027323, R56DE025597, R01DE026730, R01DE021683, R21DE024230, U01HL099776, U24DE026914, R21DE019274, U01HL099999, R01CA86065, R01HL058770, NIAK99AG049958, P50HG007735, R01 R055650, R01AR06371 and S10 RR02933801), the California Institute for Regenerative Medicine, the Howard Hughes Medical Institute, the Oak Foundation, the Hagey Laboratory, the Pitch Johnson Fund, the Gunn/Oliver Research Fund, a Siebel Fellowship, a PCFYI Award, Stinehart/Reed, the Deutsche Forschungsgemeinschaft and the Ellenburg Chair.

The researchers have a pending patent for the isolation, derivation and use of human skeletal stem cells and their downstream progenitors.

Researchers from the Medical University of Graz in Austria, RIKEN in Japan and the University of California-San Diego also contributed to the study.

Stanford’s Department of Surgery also supported the work.

Successfully avoiding hip replacement surgery

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Hip replacement surgery is no longer an inevitable outcome of chronic hip pain, even when arthritis has set in and told hip replacement is recommended.

4 years ago when first consulting with patients on our stem cell procedures with degenerative hip conditions, I didn’t have a lot of experience with the results. Therefore, I could never be confident that it would help. I was more concerned about the expense of the procedure and what if it didn’t work? I was more concerned about how upset the patient would be with me having paid a substantial amount of money with no results. Therefore, I would say something to the effect of… “There is a good chance it could help, but I’m not sure. It might not work at all. In fact you better think it over long and hard this week. Talk it over with family and get back to me.”

I can clearly recall Mrs. Johansen, a 66 year old grandmother who simply wanted to travel to see her grandchildren in other states, but was not able to do so because of her ailing hip. I can recall having that same conversation as mentioned earlier, asking her to think it over all week with family input and consulting with her orthopedist. What I learned. Very good, loving, compassionate, well meaning family members and friends talked her out of an expensive, non-FDA approved stem cell procedure for her hip, and to put her trust in the joint replacement. Because that was at least a “for-sure” thing.

I didn’t hear back from the family of Mrs. Johansen until about 6 months later. Her daughter with great concerned called and wanted eagerly to speak with me as soon as possible. I remembered the family and called at my first break. I was sad to hear of the events that occurred following her hip replacement. It was explained to me that her procedure seemed to go just fine, her recovery was quick and was sent home the next day. Unfortunately, the following days didn’t go so smoothly. she soon had increasing pain and swelling round the hip, she then developed a fever and felt sick to her stomach, soon she was dizzy and feeling faint. She called her daughter and within an hour she was being sent by ambulance to the ER - as you may have guessed, she developed an infection at the surgical site and the infection had gone septic. She was immediately started on IV antibiotics until stable and then had to have the hip replacement operated on again to clean out the infection that had spread all throughout the hip.

It was determined that the replacement was going to have to come out as they could not completely remove the infected areas of the hip. They removed the hardware, but because of the fragility of the bone after the removal, it was decided to close her up without any hip at all. She was released from the hospital on bed rest (obviously, she has no hip). So, there she lies in a bed for weeks trying to recover from the infection so they can proceed with another surgery to replace the hip. After 4 weeks of antibiotic therapy, she appeared to be clear of her infection and they proceeded to surgically implant a new hip for the second time.

Her daughter tells me that the second hip at least didn’t get infected and she’s on round-the-clock antibiotic therapy likely for the remainder of her life. In addition the hip didn’t take very well, in her weakened condition the bone and metal didn’t seem to be “getting along” and she’s unable to bear much weight on the hip because it seems to slip around, feels unstable and yes it hurts.

That’s when I finally decided I need to be more confident in my recommendations. I have since learned that 3-4 out of every 100 hip surgeries will get infected with similar results, AND 1 out of every 400 of these surgeries results in death of the patient within the first 90 days following the procedure.

Here’s the big point: At least if the stem cell treatment doesn’t give the relief necessary, you can always have a hip replacement. But, if you have a hip replacement, there’s no going back, there’s no stem cell treatment that can fix a botched hip surgery. With a consistent success rate of 81% of hip patients, I am much more confident in my approach today as I should be. We get great results and best of all, no surgery!

Amen? Amen.

Dr Bean

Got Knee Arthritis?

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Intra-articular injection of autologous adipose-derived stromal vascular fractions for knee osteoarthritis: a double-blind randomized self-controlled trial

First Online: 14 August 2018

Abstract

Objective

The purpose of this study was to compare the clinical and radiological efficacy of autologous adipose-derived stromal vascular fraction (SVF) versus hyaluronic acid in patients with bilateral knee osteoarthritis.

Methods

Sixteen patients with bilateral symptomatic knee osteoarthritis (K-L grade II to III; initial pain evaluated at four or greater on a ten-point VAS score) were enrolled in this study, which were randomized into two groups. Each patient received 4-ml autologous adipose-derived SVF treatment (group test, n = 16) in one side of knee joints and a single dose of 4-ml hyaluronic acid treatment (group control, n = 16) in the other side. The clinical evaluations were performed pre-operatively and post-operatively at one month, three months, six months, and 12-months follow-up visit, using the ten-point visual analog scale (VAS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the knee range of motion (ROM). The whole-organ assessment of the knees was performed with whole-organ magnetic resonance imaging score (WORMS) based on MRI at baseline, six months and 12-months follow-up. The articular repair tissue was assessed quantitatively and qualitatively by magnetic resonance observation of cartilage repair tissue (MOCART) score based on follow-up MRI at six months and 12 months.

Results

No significant baseline differences were found between two groups. Safety was confirmed with no severe adverse events observed during 12-months follow-up. The SVF-treated knees showed significantly improvement in the mean VAS, WOMAC scores, and ROM at 12-months follow-up visit compared with the baseline. In contrast, the mean VAS, WOMAC scores, and ROM of the control group became even worse but not significant from baseline to the last follow-up visit. WORMS and MOCART measurements revealed a significant improvement of articular cartilage repair in SVF-treated knees compared with hyaluronic acid-treated knees.

Conclusion

The results of this study suggest that autologous adipose-derived SVF treatment is safe and can effectively relief pain, improve function, and repair cartilage defects in patients with knee osteoarthritis.

Keywords

Osteoarthritis Adipose-derived stromal vascular fractions Intra-articular injection Articular cartilage 

Pro Athletes and Injuries

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Professional athletes are heavily invested in their bodies, after all it's that body and their determination that got them where they are.  But once they enter the big leagues, it's a team of professionals that will try and protect that franchise player.  

It's becoming obvious that surgery is a one way trip to the bench on "injured reserve" and the remainder of their career in question.  Where there is a problem, a solution is bound to appear.

Enter stem cell therapy - more and more athletes are trusting their own bodies to heal and mend their injuries, taking great steps to explore these modern cell therapies.  Extracting and isolating the bodies own healing cells called stem cells is increasingly being utilized as an alternative to surgery and for good reason.  It's working!  

Check out the list here (Courtesy Cade Hildreth of BioInformant) of the latest list of professtional athletes choosing stem cell treatments over surgery to heal their injuries.  

Blessings,

Dr Bean

 

Nutritional Considerations in Stem Cell Treatments

written by Stem Cell The Magazine 

June 22, 20181. Quadriceps Muscle Lack of Oxygen Followed by Injury to the Muscle After Treatment

Stem cell treatments are a good thing – but in the rare case that you need an option because stem cell doesn’t work for you – ask your doctor to offer a treatment that would increase blood supply to the area.

After there’s been a lack of oxygen in a muscle or tissue, the body compensates by sending in more blood flow to the area. Sometimes doctors may use a treatment to increase circulation to tissue that’s been deprived of oxygen.

For example, one type of treatment is called extracorporeal shock wave treatment. This is used for heel spurs, plantar fasciitis and other tendon problems. A shock wave is used that brings in new blood vessels to the area – they sprout up as a result of this treatment.

Adipose stem cells also will have similar anti-inflammation effects and bring in new blood supply to the area that needs regeneration.

Scientists at the China Medical University and doctors at Kaoshsiung Chang Gung Memorial Hospital in Taiwan were thinking progressively when they thought of combining the two treatments together. Even though the study they ran was an animal study, it shows us the potential of combining treatment.

By combining extracorporeal shock wave treatment with stem cells, the results were superior to either treatment by itself. The quadriceps muscle damage was reversed and the amount of blood circulation to the area was greater after the injury when both treatments were used together.

If your stem cell doesn’t work, you might consider using some of the same type of thinking that these researchers used. Since they used two treatments that decreased inflammation, it’s possible that decreasing inflammation in your own body could make an impact.

This does make a lot of sense actually and you may want to check out our article on inflammation and stem cells. If you can decrease the inflammation in the body, stem cells can work better. There are several ways to do this. For example, eating an anti-inflammatory diet would be one of the first things to start with. This is a diet that avoids sugar and processed foods as well asoils that increase inflammation such as canola oil, vegetable oil or other “seed” oils. Olive oil and coconut oil are not inflammatory.

The second thing to try might be to get an ALCAT blood test that will identify the foods that are causing inflammation reactions to occur in your body. Then systematically you would eliminate these foods from your diet for a few months

The third thing to do to reduce inflammation is to lose weight if your weight Is higher than what it should be. Reducing the belly fat will reduce the amount of inflammation that is generated in the whole body because the fat cells produce inflammatory factors.

You have a lot of control over inflammation in your body – and thus can directly control the rate of your stem cell multiplication.

2. Vitamin D Therapy

Scientists are still learning the benefits of stem cell growth factors. In the early days of stem cell treatments, growth factors weren’t used to support the reproduction of the stem cells. Consequently, the treatment either didn’t work or it worked – there was no in between.

The scientists increased the signaling to Vdr by adding the vitamin D3 agonist called calcitriol. An agonist is something that makes everything go well in the way it should go. The result of this was that the stem cell colonies in the bone marrow and liver increased their numbers.

The bottom line here is that if stem cell doesn’t work for you during the first treatment, check to see that growth factors can be added to the second or additional treatments you receive. It may not be calcitriol but other growth factors that are needed to create better results.

3. Supplementation with Specific Nutrients

There are other nutrients that have been found to increase the stem cell growth rate – ones like astaxanthin found in salmon roe, crab, algae, red trout, shrimp and lobster, and zinc.

The astaxanthin has the ability to make adipose stem cells turn into nervous system stem cells called oligodendrocytes.

Thus, this nutrient would be a potential good addition to one’s diet if the stem cell treatment doesn’t work for your nervous system disorder such as multiple sclerosis.

Zinc is found in eggs, seafood and meat as well as Rocky Mountain oysters (testicles from mammals). This unusual ‘oyster’ dish is found in areas of the country where young animals are castrated, such as in the West and in western Canada.  Korean scientists found that zinc creates new bone cells in mesenchymal stem cells and that higher amounts of zinc in the diet meant better differentiation of stem cells.

Again, this could potentially mean that zinc supplements might help when your stem cell treatment doesn’t work.

The bottom line here may be that your nutritional status is going to seriously determine whether or not your stem cell treatments work or not.

And this also makes a lot of sense because there’s a reason or probably several of them why we have recommended daily allowances for vitamins and minerals in the body.

However, it’s not just vitamins and minerals that matter most. It’s also what’s in the foods you eat – and when you eat a high plant-based diet full of fruits, vegetables, nuts and seeds, then all those hundreds of medicinal ingredients in them such as carotenoids and polyphenols could be doing a lot more than what we know now. They could conceivably be controlling your body’s own stem cell regeneration.

Cancer Cells are manipulating you

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Once again, it has been shown in this article from Penn State U cancer cells are very manipulative.  Their cellular communication is quietly telling your T cells to take a nap.  Unfortunately this is allowing the cancer cells to flourish.  There have been a couple drugs introduced (immunotherapy) in order to activate the T cells, however once again we're talking about 100's of thousands of dollars with mixed results.  If you review the cellular profile of exosomes from mesenchymal stem cells isolated from umbilical cord blood, it would be plausible that the intravenous deployment of these exosomes may help activate the T cells, with the addition of stem cell deployment.  Theoretically this could be a wonderful alternative to traditional cancer treatments at a fraction of the costs.  Remember, this is a theoretical construct.  Don't try this at home, consult with your physician before jumping into such a treatment regimen.  

Blessings,

Dr Bean

 

Yes, your 4 legged family members can benefit from stem cell treatments

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I am often asked if we can treat their 4 legged family members, and I'm always glad to hear they have an interest in preserving the quality of life of their pets.  However, this does need to be performed by a veterinarian who has the experience working with animals.  Vet-Stem is a national network of veterinarians who are qualified to perform stem cell therapy for your animals.  

A recent article was just published in WebMD endorsing cell therapy for animals and I felt it was a positive article.  With the success rate at 88% for joint problems, that's even a bit better than we are getting clinically in our office.  It appears animals respond even slightly better than us humans.  

Feel free to leave comments on your experience with stem cell therapy on your family pets.  

Be Well,

Dr Bean

Gene editing and higher intelligence

Who would have thought editing a piece of DNA that God created or billions of years created might cause some problems, Huh?

It turns out it's not as easy as it was made out to be.  Now scientists admit it's difficult to simply cut out the exact area of mutated DNA, and in fact often thousands of DNA base pairs are often edited out by mistake rendering the cell lifeless.

Sorry, but this gene editing stuff is a long ways off before real DNA editing for the public ever sees the light of day, if at all.  This is an area that requires decades of research in order to perfect and prove safe.  We already have a product on the market by Novartis for cancer therapy when they manipulated an immune cell (CAR-T cell therapy) to target cancer cells.  Although it's not gene editing, it is manipulating the cell with a virus.  Not only is it potentially wrought with side effects, it's not that financially successful and with a price tag of $475,000 per treatment?  

Pharmacy is still trying desperately to cling to it's massive control over healthcare and delivery.  But, it's getting much harder as newer techniques of working with the regenerative cells of the body holds great promise and is succeeding to help patients get well utilizing their own recuperative powers.  To be continued...

Repair your heart - with your cells

More advancements in the field of cardiology as it relates to regeneration are not only on the horizon, but seeing success in clinical practice today.

Recently, scientists have had great success with introducing induced stem cells in the treatment of heart failure in monkeys.  I knew this would be successful, we have seen it happen dozens of times in our offices.  Patients come in with an orthopedic condition that we accept for treatment, and at the consultation we learn they also have a heart condition, ie congestive heart disease or heart failure.  This in itself is not a contraindication, but a side note.  However, it is common for these patients to improve in heart function, verified by their cardiologist when repeat ejection fraction is looked at in a routine check up, most likely from the IV portion of the treatment.  We had a patient, Don, a retired executive who discontinued most all activity do to his heart condition.  He explained that his LVEF (left ventricular ejection fraction) had been hovering around 45% for the last 6 months, down from 55% the year prior.  We treated his knee condition with SVF and an IV.  It wasn't a month later when we checked up on him that he explained that his LVEF had gone up to 60% and his cardiologist was in disbelief.  He had actually repaired his heart.  This is not an uncommon story by the way.  This is common place for physicians practicing regenerative medicine.  Although not approved for heart failure by the FDA, it is non-the-less working.  

Some feel it is do to the differentiation of the stem cells into cardiac cells, others are not so sure.  I feel after reading several case studies, research studies along with animal models, the main reason for the improvement is the secretory extracellular vesicles that are relaying the messages of repair. This is the most likely cause of improvement, as the stem cells when administered IV are not going to reach the cardiac cells in a great enough abundance to really have a dramatic presence.  However, the extracellular vesicles (EV's - the regenerative signaling of the stem cell) will be secreted by these infused stem cells in the billions.

Pass it on...