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
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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...

Traumatic Brain Injury - a novel approach

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The most difficult traumatic brain injuries (TBI) to treat successfully are the individuals who have had their injury several months or worse, years earlier.  The typical response to an injury of the brain is scar tissue and other connective tissues that do not resemble normal brain matter.

One progressive method is to introduce stem cells, either bone marrow stem cells (BMSC), adipose stem cells (ADSC), or umbilical cord stem cells (UCSC) into the intrathecal space (the area just outside the spinal cord, within the sheath that covers the spinal cord).  This is the space that contains the cerebral spinal fluid (CSF).  This attempt was a natural choice as it was widely accepted early on that stem cells do not cross the blood brain barrier (BBB).  More recent evidence suggest that they actually do, just not efficiently it does require some migration of the stem cells to get across the BBB.

More recently it has been accepted that it is not the injected stem cells that are differentiating into the new nerve tissue, rather the presence of the stem cell activates the cells around them to become active.  Further, the stem cells release messenger molecules that up regulate the brain tissue to grow and repair, not in an uncoordinated random way, but in a very controlled regenerative process that repairs brain matter.  The challenge has been, how to get the stem cells to the areas of the brain that need them the most?

Observation of dozens of cases of TBI improvement with ADSC deployment intravenously had been recorded.  How did the stem cells find their way to the brain?  Stem cells migrate.  They have amoeba and immune cell type mobility.  They can migrate to the area of dysfunction and begin the repair process.  In addition, the exosomes secreted by the stem cells are very small, between 80 - 250 nano-meters.  That's small.  Small enough to cross the BBB with ease, therefore it is postulated the regenerative process of the brain is likely more do to the influx of exosomes in the presence of stem cells that's making the difference.  And in fact, we recommend an iv push of exosomes produced by young umbilical stem cells at the same time as the ADSC are deployed/infused.  

What's more, I have a unique slant on the process that can significantly increase the likelihood of recovery.  We know coffee has a unique ability to decrease blood flow to the brain, which is why if you suddenly discontinue regular coffee use, an individual can get a bad headache as the blood comes rushing back to the brain causing swelling.  Utilizing this reaction, drink 3-4 cups of coffee each morning for a month leading up to the procedure.  Have your last meal 48 hours prior to the procedure.  Have your coffee the morning of the procedure, then discontinue all together until a raging migraine appears, naturally this is very uncomfortable for about 48 hours until the blood flow can regulate itself at which time the headache will disappear.  It is during this headache when the stem cells will quickly migrate to the brain as well as increased secretion of exosomes and other extracellular vesicles.

Lastly, fasting for 48 hours prior to the procedure will also induce autophagy, increase natural stem cell production and activation when we harvest them from the mini-liposuction procedure.

Let me know if you have any questions or comments.

Dr Bean

Crohn's disease patients effectively mobilize peripheral blood stem cells to perform autologous haematopoietic stem cell transplantation

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Crohn's disease is a very horrible condition of the intestines.  It's can make any errand away from home a stressful and often embarrassing endeavor.  Also, for most it can be very painful and gut wrenching.  Several types of food can be very unpleasant.  During flares, life can be downright miserable.  

It's encouraging to see that stem cell therapy is gaining favor in light of several new reports showing promise, and even better than pharmaceutical drugs that can cost over $10,000 a month.  Even more encouraging, there are stem cell resources in the body that can treat the underlying cause of Crohn's disease.  Stromal vascular fraction is recovered by processing fat tissue after a mini-liposuction procedure that is very non-invasive and takes about 30min.  After, the fat is off to process in the lab.  And then an hour later the cells are ready to be administered through iv for about 45min.  The stromal vascular fraction (SVF) has remarkable attributes.  The stem cells and extracellular vesicles are able to down regulate immune cells through a series of cell-to-cell communications.  

The adipose (fat) tissue stem cells seem to be especially gifted in their ability to modulate the immune system in a beneficial way.  And not just to benefit Crohn's, but a whole host of immune system dysfunctions.  

This is so encouraging for those who suffer with immune system problems.  A cure is on the way and it's looking like it's going to happen.  I do believe in the near future this will be a very common procedure to cure autoimmune diseases.

In search of the Holy Grail of Healing - Part 2

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Mesenchymal stem cells are fabulous mono-nuclear cells found in all tissues of the body.  they are found in abundance in the stroma of adipose tissue that I touch on in Part 1.  In my research on stem cells I came upon a realization.  Much like chicken soup, if we focus only on the chicken and study it's contents.   I'm sure we would be discouraged with it's inability to reduce the symptoms of a cold/flu when isolated from the broth.  But when the broth is combined with the chicken, we get a whole new clinical outcome.  So it is with the stem cell, by itself it is very cool with amazing properties, but without it's broth it is less effective in a clinical setting.  Within the broth of the stroma lives an even smaller subset of vesicles that have illuded scientists for years.  I can remember clearly being taught that these extracellular vesicles (EV's) were the garbage trucks that transported garbage and debrit out of the cell.  Boy, they were WAY wrong.  These EV's are the communication system of the cells.  The EV's are critical for gene expression and behavior of stem cells and all other cells in the body.  They may communicate with a cell right next door, or it may communicate with a cell on the opposite end of the body.

EV's in recent years have almost stole center stage away from the stem cell as it turns out, the reason stem cells are so wonderful, may not be entirely because they are so awesome, but becuase they secrete awesomeness in the form of EV's.

In fact, when EV's are isolated, which is quite difficult to do by the way as they are very tiny bubbles, many many microns smaller than a cell.  They have the same abilities to change behavior and gene expression in cells as the stem cells.  You can effectively remove the stem cell altogether and just release the EV's in concentrated form and create the same effect, at leased in vitro.  

It's an exciting field that is just ramping up, clinical trials are just getting underway for therapeutic use.  I read an article recently posted, one of the Green bay Packers new players from the Seattle Seahawks (can't believe they let him go!) - Jimmy Graham, just returned from a cell therapy program in the UK utilizing just EV's, no direct injections into his ailing knee, simply an iv of EV's and apparently in his own words is "feeling great".  He remarked after the therapy he had watched a movie and afterwords he stood up and felt no knee pain at all which was not the case just prior.  Over a year has gone by and he's still pain free.  Time will tell if it's only the anti-inflammatory effect or some kind of true healing that took place.  But I know I'm a believer, it just makes sence when you study it.

In search of the Holy Grail of Healing - Part 1

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It has been my lifelong journey to find the fountain of youth.  I've spent the last 25+ years exploring natural healing and regeneration.  I came up wanting every time.  Spent thousands of hours, thousands of dollars exploring and researching trending stories, tropical berries, rare earth gases, ionizing waters, vitamin regimens, spinal manipulative techniques, chi activation, functional medicine, meditation and the list goes on.  The pursuit has always been to activate and or release the innate regenerative properties of the body, similar to a time when it was not ever a thought.  You know, like you did when you were twelve.  The ability to heal with great enthusiasm fades as we age, and it's heart breaking.  Just as we transition to a time when we have more time, the so called "golden years" we seem to be instead of ramping up our exploration of this world we are besieged by an onslaught of debilitating illnesses, aches, pains, moans and groans.  

How is it that along our path our bodies decided, without consultation by the way, to fall into a state of not only disrepair but into the lion's den of medical miss-information in the guise of science.  Science, as I have learned is malleable, plastic, persuasive and even deceitful when in the hands of financial concerns of shareholders.  Why is it that you go to the doctors with a belly ache and multiple vials of blood, a CT and Ultrasound and $2,000 later you're told there's nothing wrong with you and you have a stomach virus, instructed to go home and take the medications, rest and everything will be fine - "Thanks for doing business with us!" is what they should say, because that's what you did, you did business with them.

Every century or so a discovery is found that changes everything.  We see a "paradigm shift".  Something is discovered that changes everything, it refocuses the entire science and medical community in a new direction.  This is occurring as I write this letter.  Just think "biotech", how's the biotech industry?  It's BOOM city.  Billions are flowing into the new biology of healing with the re-discovery of cell biology and innate healing.  The science of regenerative medicine is exploding and heading to your town despite the criticism of old hard-liners who do not want anything to change because they are very comfortable doing things just the way things always have been done.  

Change is uncomfortable and requires learning, study and re-tooling.  Those who re-tool and learn what the cell biologists are bringing to light are the early pioneers in regenerative medicine.  Specifically I'm talking about cell therapy.  But more precisely, stromal vascular fraction (SVF).   It is the SVF that is the stuff of legends, teaming with stem cells, progenitor cells, growth factors, cytokines, exosomes, etc.  This stroma is of natural origin, it comes from you within the adipose tissue.  Yes, I mean your fat!  As it turns out your fat is absolutely an amazing organ - and yes it's considered an organ by many biologists.  Strangely enough, it was really the frequent discovery by plastic surgeons that fat is an amazing substance to work with. The fat tissues throughout your body has some amazing properties.  I wont bore you with the details however, feel free to research SVF on you own on the PubMed website, research is no longer the privilege of the educated but is available to anyone willing to put in the time.

The physician's office today producing SVF from the tissues of the patient are wielding an amazing regenerative tool in the fight against damaged, dying and decaying tissues in the body.  It can be deployed (injected) into damaged tissues, it can be deployed intravenously for systemic disease conditions, auto-immune conditions, traumatic brain injury and on and on.  In the near future you will not be given a pill, you'll be deploying your cells.  But here's the kicker.  It's going to be kept out of the hands of your local mainstream medical clinics and hospitals.  Why, if it's so great?  Because, if you think about it, these are YOUR cells.  Not a medication, not a synthetic chemical, not titanium hardware, not another million dollar body scanner.  Can you begin to see why this new paradigm is going to struggle to get to the surface?  Billions are being poured into research by big pharma to find a cell therapy that can be synthesized, bottled and given a lengthy expiration date to be put on the shelf for sale.  Sorry, but you can't synthesize the bodies innate healing powers, it's not reproducible.  It can only be deployed appropriately.  Not to be duplicated.

It's an exciting time to be a pioneer in the field of regenerative medicine and I'm having the best time of my life exploring what is possible.  I see the difference it makes in the lives of those we serve.  I cheer the scientists and biologists who continue to advance this field in the face of heavy criticism of big pharma's influence throughout the medical community and mass media who have billions upon billions at stake.  

Heart Patients can breathe a sigh of relief

The stem cells and other progenitor cells concentrated as SVF or Stromal Vascular Fraction from the patients fat after a mini-liposuction has the potential to radically alter the way patients are treated following a heart attack, stroke, angina, or heart failure.  Other attempts at stem cell therapy have also shown to be beneficial as well.  But the greatest concentration of these regenerative cells and stem cells are found in the fat derived stromal vascular fraction. 

Experts say initial findings suggest those who have suffered crippling heart failure can go on to lead normal lives.

Dr John Hung, a cardiology specialist working on the trials in Edinburgh, said that because anyone can have the treatment it has the potential to save huge numbers of lives and at the same time slash the NHS bill for the future care of heart failure patients.

He added: “We think about one in five people who survive a major heart attack are likely to benefit from the therapy, and this could mean hundreds of thousands in the UK or many millions across the world.

"There should also be healthcare savings from the reduced costs for medication, ongoing treatment and recurrent hospitalisations.”

One patient who was given a 50-50 chance of surviving five years after suffering a major heart attack, because of the damage it caused, has spoken of his gratitude of being given the radical treatment.

One patient called Bill, not his real name, now has almost normal heart function and he believes he has been given a second chance at life.

We are now offering this life saving therapy in our Seattle and Salt Lake locations.  Contact us soon to see what we can do for you or a loved one.

Tarek El Moussa, reality show real estate mogul gets out stem cell procedure done for his lower back pain.

We have performed dozens of spine related stem cell procedures over the last couple years.  Having been involved with spine care over the last 20+ I can say I feel more confident than ever dealing with complicated spinal conditions then ever before.  And more and more celebrities are taking notice.

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if you are suffering with spine related problems please connect with me and let's talk it over.

There'sa lot to be optimistic about. 

Regards... 

Stem Cells - only a small portion of the magic

It's is the unfortunate philosophical bent of most scientists to have a reductionist mindset.  That is to narrow their vision down to the least common denominator of a substance looking for the one thing that makes something work.  Learning more and more about less and less until they know absolutely everything about nothing at all.  Not to disparage this practice as it does add to the body of knowledge. 

However, it is this myopic tunnel vision that is plaguing our research facilities.  This is also true of stem cell research.  So much effort goes into investigating the nature of the "stem cell" as the Holy Grail of regeneration.  But what of the other cells it communicates with?  What of the exosomes that it uses to transfer DNA and other proteins.  What of the extra cellular matrix and environment of the cell?

Let me introduce you to Stromal Vascular Fraction (SVF).  This is the end product after a simple mini-liposuction procedure and subsequent cell processing in a lab.  The SVF is the "soup" that is concentrated for the purpose of cellular regeneration.  It can be used for degenerated joints as well as a number of auto-immune, neuro and other degenerative conditions.  The "Healing Miracle" documentary that came out recently had a lot of good information as well regarding its clinical use.

At the same time, SVF is a bit of a taboo in arenas that are heavily influenced by big pharma.  Why?  Because there is absolutely not a dime to be made for these folks.  As such, they never turn down an opportunity to shun it's practice as we saw in a Consumer's Report article that was completely and factually untrue as expressed by scientist everywhere. So don't expect Eli Lilly to fund a double blind, placebo controlled, randomized crossover clinical trial to show all the benefits of this "all natural" organic product that can't be patented. 

The attached paper is a wonderful review of the nature of stromal vascular fraction (SVF) and the conditions it appears to be naturally reversing.  Enjoy

Stem Cell for Traumatic Brain Injury (TBI)

Once again we are seeing incredible progress with the iv administration of adipose (fat) derived stem cell on the recovery of brain injury, such as in stroke, trauma, lack of oxygen, or heart attack.  Most recently an 11 year old who suffered cardiac arrest after a freak accident involving a pellet gun that misfired and logged a pellet in his heart.

Although he survived the ordeal, he was left with considerable brain injury.  However, fortunately they were alerted to a stem cell facility outside the US that had the capability to extract stem cells from the boy's fat.  The cells are then culture expanded to create hundreds of millions of cells to then administer them through an iv.  

What most people are unaware is that this process can be performed here in the US.  In fact, here in Salt Lake City were are performing this very procedure.  The only difference is that we do not need to culture the cells.  In our proprietary cell processing, as performed in all Cell Surgical approved locations, we are able to not only concentrate the stem cells, but also the other related cells, cytokines, growth factors and adipocytes that are crucial to healing and repair.

We stand in bewilderment of the innate power of the body, it is only now that we are learning ways to work with it to optimize the regenerative powers of the body.  These are glorious times.