Apr
25
2020

Exosomes can Regenerate Your Stem Cells

By | Anti-aging medicine, Arthritis, blood brain barrier, Diabetes, exercise, fasting mimicking diet, Fitness, Heart Disease, immune system, Inflammation, kidney disease, lifestyle, mitochondria

Dr. Douglas J. Spiel gave a talk on how exosomes can regenerate your stem cells. In essence, this was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. His original topic was: “Placental MSC Exosomes for Longevity and Chronic Disease”. Notably, MSC stands for “mesenchymal stem cells”. Dr. Spiel recommended this website to look at applications of exosome therapy.

Essentially, what scientist found is that certain factors from stem cells can activate your own stem cells to regenerate tissues that grow old. These factors are messenger RNA (mRNA) and micro RNA (miRNA), which come as tiny particles of 40‐100 nm.

Advantages of administering exosomes

To emphasize, exosomes can be given systemically as infusion, and they can regenerate your stem cells, if they are in need of treatment. They cross the blood brain barrier, so it is possible to treat brain diseases. That is to say, there is no first-pass removal in the lungs as it is with mesenchymal stem cells (MSC). The potency is related to the age of the donor and his/her stem cells. Notably, exosomes are easy to store, freeze and administer.

Exosomes influence the growth of target cells and promote regeneration. In addition, exosomes stimulate immunomodulation and have anti-inflammatory and anti-fibrotic properties. To clarify, the only limitations are that the strength of the exosomes is related to the age of the blood donor. The exosome fraction comes from mesenchymal stem cells. That is to say, it circulates in the plasma portion of the blood, which is obtained by spinning blood cells down in a centrifuge. To emphasize, exosomes can regenerate your stem cells.

Applications of exosomes for various clinical conditions

Joint inflammation

Mesenchymal stem cells are useful to treat arthritis. But it is important to realize that exosomes from mesenchymal stem cells are doing the same by stimulating the body’s own stem cells situated in the joints. In fact, several target cells have been identified that are stimulated by exosomes. These are chondrocytes, chondrocyte progenitor cells, cartilage-derived stem cells and synovium‐resident multipotent progenitor cells. In addition, other target cells are osteoblasts and osteoclasts in resident MSC within the subchondral bone and chondrogenic cells in the knee joint.

Disc degeneration  

Degenerative intervertebral discs respond to exosome treatments. The IL1 beta cytokine is involved in intervertebral disc degeneration. Exosomes inactivate these cytokines and have antioxidant and anti-inflammatory effects. Exosomes are not all the same. Different sub-fractions were isolated that have anti-inflammatory, immune-stimulating, antioxidant and other effects on the body.

Aging research

Researchers were able to pinpoint aging to various factors that contribute to premature aging. To clarify, when there is a decrease of catabolic processes and an increase of anabolic processes, an older person can combat premature senescence. Another key point, aging is also linked to redox homeostasis. Simply put, oxygenation processes in the body need to be balanced by reduction processes. This keeps the body in a healthy state. ADP/NADH production can be stimulated by exosomes.

Longevity comes from good lifestyles

With the use of exosomes, the aging process slows down, as oxidative stress is neutralized, damaged mitochondria are removed and cellular debris as well. That is to say, this improves inflammation and premature aging.

As has been noted, in the past 200 years life expectancy has doubled in most countries. 4 areas where longevity is particularly common are: Okinawa, Japan; Sardinia, Italy; Nicoya, Costa Rica and Loma Linda, USA. Only 7% of longevity stems from genetic factors, the rest is from lifestyles we adopt. In the final analysis, people who die prematurely followed a very poor lifestyle causing them to develop diseases, which ultimately killed them.

Clinical diseases from aging

Ultimately, advanced aging puts you at risk of getting cardiovascular disease (heart attacks and strokes), cancer and neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease). From the third decade onwards, there is the risk of bone loss, which causes osteoporosis. As has been noted, loss of cartilage causes osteoarthritis. Loss of muscle strength and muscle mass is called sarcopenia. With aging there is often an accumulation of abdominal fat. Hormones are disbalanced. Blood pressure is often elevated and blood lipids as well. Insulin resistance can develop and the blood vessels become stiffer. This causes heart attacks and strokes.

The details of the aging process are much more complicated than originally thought of. There is a combination of aging of the DNA, mitochondrial aging, stem cell exhaustion and a change of intercellular communication due to dysregulated endocrine signalling. In addition, there is a decline of the immune system and epigenetic factors that can turn off longevity genes.

Oxidative stress as a cause of premature aging

Dr. Spiel pointed out that reactive oxidative species (also known as free radicals) cause damage to mitochondria and mitochondrial DNA. But we need the energy from the mitochondria for a comfortable life. In essence, antioxidants can neutralize free radicals. Age-related conditions due to oxidative stress are: cardiovascular disease, chronic kidney disease and type 2 diabetes, chronic obstructive pulmonary disease, cancer, neurodegenerative disease, frailty and sarcopenia. Surely, both reactive oxygen and reactive nitrogen are free radicals. They have one or more unpaired electrons and all aerobic body cells produce them. Reactive oxygen and nitrogen species (RONS) cause oxidative damage to our cells and contribute to the development the diseases just mentioned.

Antioxidants help to prevent diseases

But antioxidants can contain these free radicals in various ways. The body has five built-in enzymatic ways to protect itself and five non-enzymatic ways (bilirubin, vitamin E, beta-carotene, albumin and uric acid). In addition, there are antioxidants that a person can take as supplements to inactivate RONS. These are: vitamin C and E; phenolic antioxidants like resveratrol, phenolic acids, flavonoids, oil lecithin, selenium, zinc and drugs like acetylcysteine.

Without control of the oxidative stress RONS can lead to cellular senescence and chronic inflammation. This leads to a vicious cycle where chronic oxidative stress and inflammation feed on each other leading to premature diseases.

Causation of several diseases

As we age, the body reduces the inborn antioxidant enzymes (superoxide dismutase and glutathione peroxidase). Before we can understand how to live longer, we need to be aware what happens in various health scenarios as follows.

  • The lack of inborn antioxidant enzymes leads to vascular endothelial dysfunction, high blood pressure and premature hardening of the arteries. This can become a precursor to heart attacks and strokes.
  • Elevated blood sugar in the case of type 2 diabetes leads to increased sugar concentration of body cells and formation of free radicals.
  • Oxidants from cigarette smoke activate macrophages and epithelial cells to produce inflammatory cytokines. Continued smoking releases proteases in the process that break down connective tissue and cause emphysema and COPD.

There are more diseases

  • Chronic kidney disease comes from oxidative stress affecting the filter units of the kidney, called glomeruli. With a lack of blood supply to the kidneys secondary high blood pressure develops and endothelial dysfunction. It also leads to chronic inflammation.
  • In the brain oxidative stress leads to cognitive impairment and dementia.
  • Oxidative stress and chronic inflammation are important ingredients for the development of cancer. RONS and cytokines release NF-kB, which activates cancer genes. RONS can also directly attack the DNA of cells and cause cancer through carcinogenesis.
  • Sarcopenia and frailty come from the action of RONS on the skeletal muscles. In old age there are less inborn antioxidants available. This leads to decreased muscle quantity or sarcopenia. Eventually frailty results with the risk of falls and fractures. 

Preventative measures for slowing the aging process

There is a number of steps that in combination help to slow the aging process.

  • A Mediterranean diet combined with a fasting mimicking diet or other calorie restricted diet
  • Regular physical activity
  • Cognitive training
  • Vitamin D3 supplementation
  • Reducing your risk to develop vascular disease
  • Certain drugs turn on the longevity gene (metformin, rifampin)
  • Spiel warned that due to limited compliance and variable response these steps alone may not be enough to prevent age-related problems

How to live longer

It is important to recognize the importance of antioxidants to counteract the development of these diseases. As already mentioned, the following counter the effect of free radicals: vitamin C and E; phenolic antioxidants like resveratrol, phenolic acids, flavonoids, oil lecithin, selenium, zinc and drugs like acetylcysteine. Mesenchymal stem cells can also stop the action of free radicals. In addition, exosomes, which  are products of mesenchymal stem cells can do the same. Mitochondria, the power houses within the cells, create energy, but also release free radicals. In his clinic Dr. Spiel administers intravenous exosomes to counter the oxidative stress. Numerous studies linked mitochondrial dysfunction to various age-related diseases. There are markers in blood tests that the physician can order to analyze malfunctions in the body. Dr. Spiel showed 4 slides that contained a lot of medical information that is too technical. I omitted it for this review.

Intravenous infusions of exosomes

The important thing to remember is that epigenetics can be changed by exosome infusion and lifestyle changes mentioned above. Dr. Spiel said that generally he uses 15 ml of exosomes by intravenous infusion every 12 weeks for longevity and performance enhancement. This treats conditions like infertility, osteoporosis, osteopenia, heart, liver and kidney weaknesses. Here is the dosing for intravenous exosomes by weight:

20-50 lb: 5 ml; 50-90 lb: 10ml; more than 90 lb: 15 ml; more than 220 lb: 20 ml. Unfortunately, one exosome treatment costs between 500.00 and 922.00 USD, an amount that most people cannot afford.

Contraindication to the use of stem cells or exosome therapy

It is important to realize that a person who has cancer should not receive either mesenchymal stem cells or exosomes. Indeed, exosomes do not differentiate between cancer cells and healthy cells, but stimulate cell division. For the same reason people with myeloproliferative disease (sickle cell anemia, bone marrow dysplasia) should also not receive exosomes. To clarify, other conditions where the physician will not order exosomes are primary pulmonary hypertension, acute bacterial infection or an immune-compromised state. In addition, macular degeneration with neovascularization is also a condition where the health professional does not administer exosomes.

Exosomes can Regenerate Your Stem Cells

Exosomes can Regenerate Your Stem Cells

Conclusion

Dr. Douglas J. Spiel gave a talk on how exosomes can regenerate your stem cells. Specifically, this was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. Dr. Spiel explained how disease processes age our organs. Reactive oxygen and nitrogen species (RONS) cause oxidative damage to our cells and contribute to the development of diseases. This involves the mitochondria in the cells as well. The good news is that a healthy lifestyle can counter these damaging processes to a certain extent. But it takes another step to re-establish the balance of our cells, exosome infusions. Exosomes are tiny particles that are shed by stem cells and that circulate in the blood. They can reenergize stem cells that are ailing to become functional again.

Expensive exosome infusions

He recommended an infusion with exosomes every 12 weeks for maintenance of good health and as a “fountain of youth”. Obviously, there are some limitations. As mentioned, it is not suitable for all patients, like cancer patients, patients with sickle cell anemia, acute bacterial infections or pulmonary hypertension. In addition, it is also not a treatment which many patients will seek out as the cost is prohibitive. One exosome treatment cost between 500.00 and 922.00 USD, an amount that most people cannot afford.

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Feb
15
2020

Rheumatoid Arthritis Treatment by Regenerative Medicine

By | Arthritis, autoimmune disease, fasting mimicking diet, Nutrition, stem cells

Dr. David Lans gave a talk at a conference in Las Vegas about rheumatoid arthritis treatment by regenerative medicine. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. The full title of his presentation was “Rheumatoid Arthritis, A Regenerative Medicine Approach”.

Dr. Lans is a rheumatologist and Assistant Clinical Professor of Medicine at the New York Presbyterian Lawrence Hospital, Bronxville, NY.

Introduction

Rheumatoid arthritis is a worldwide immune disorder. About 1% of the general population suffer of this illness with a female to male ratio of 3:1. Typically it can affect  the synovial membranes of all joints. To clarify, the presentation is usually symmetrical, but in 40% of all cases this systemic inflammatory disease can also involve other tissues and organs. 70% of cases have a positive rheumatoid factor (RF) in blood tests. However, a newer, more specific blood test for rheumatoid arthritis is anti-cyclic citrullinated peptide (anti-CCP). Symptoms of rheumatoid arthritis are anemia, fatigue, malaise, joint pain and joint stiffness. Inflammatory blood markers are positive.

Causes of rheumatoid arthritis

Genetic causes play an important role in the causation of rheumatoid arthritis. Over 100 genes  can increase due to genetics. Twin studies showed that the concordance rate to develop RA is only 15-20%. Certainly, this means that in order to develop RA you need a double hit: the genetic vulnerability for RA and also an environmental triggering factor. Meanwhile, here is a list of environmental risk factors:

  • Smoking
  • Gum disease (chronic gingivitis)
  • Any chronic infection
  • Dysbiosis in the gut
  • Environmental toxins
  • Heavy metal toxicity
  • Poor diet and nutrition

In other words, the common denominator to all of these environmental risk factors is the disruption of the mucosal integrity. In fact, this starts the process of chronic inflammation and autoantibodies (like RF and anti-CCP) resulting in chronic synovitis.

How inflammation travels from mucosal surfaces to the synovium of joints

Inflammation in gums, lungs or gut can travel via the blood and the lymphatic system into periarticular bone. This leads to bone and cartilage damage. Consequently, the bone destruction leads to chronic synovitis. To emphasize, Dr. Lans said that no patient with rheumatoid arthritis will develop symptoms of RA unless the autoantibodies have developed. In the same vein, there is a distinct preclinical period of RA with positive blood tests for RA, but absent clinical symptoms.

Prevention of synovitis through a preventative program

It is important to realize that because of this time relationship there is room for a preventative program where patients are taught the importance of dental hygiene. Another key point is that good health habits and nutrition are also important for prevention. When patients develop early-onset RA, the following measures often help to alleviate the development of symptoms: anti-inflammatory diet, stress management, intermittent fasting, a gut healing program, nutraceuticals like vitamin D3 and fish oil. Herbal therapies are also important like curcumin, Boswellia serrata, devil’s claw, ginger, Ashwagandha and others.

Conventional medicine approach versus the regenerative medical approach

To explain, the conventional treatment approach of rheumatoid arthritis is to induce a disease remission with drugs. To this effect doctors use anti-inflammatory drugs like ANSAIDs, disease modifying anti-rheumatic drugs (DMARDs). For example, drugs like methotrexate and sulfosalazine belong into this category. Unfortunately, the conventional drugs have many serious side effects that often make the rheumatoid arthritis patient’s condition worse.

In contrast, the integrative medicine approach to rheumatoid arthritis is to use dietary measures to reduce the inflammation. The fasting mimicking diet is able to reduce the severity of the inflammation in RA patients.

Other authors described the use of the Mediterranean diet to reduce inflammation. In addition, there are a number of regenerative methods that help improve the condition of RA patients.

Regenerative medical treatments for RA patients

Significantly, platelet rich plasma (PRP), peptides, stem cell therapy and exosomes are some of the modalities that show promise. (I’ll explain the meaning of exosomes later.) In addition, red light therapy and low-level laser therapy can help joint synovitis.

PRP provides growth factors to repair damaged tissues and is anti-inflammatory. Peptides consist of short chains of amino acids that have anti-inflammatory effects and promote healing of damaged tissues. Thymosin-alpha 1, Thymosin-beta 4, BPC-157, Melanotan II and FOXO4-DRI are examples of peptides used in patients. Special blood tests are used to monitor whether the treatment of RA is successful. These tests are: C-reactive protein, sedimentation rate (ESR) and Vectra. Vectra measures 12 protein markers that are important in RA.

More info about peptide therapy

Researchers noticed that peptides are very safe, but they are also very effective. HAP-1 seems to bind to synovial surfaces. RDG peptides work closely together with integrin-binding proteins. Together they have an anti-inflammatory effect in rheumatoid arthritis. They are capable of blocking both the inflammatory and autoimmune components of rheumatoid arthritis. Thymosin-alpha 1 is a peptide with powerful effects as an immune and inflammation modulator. Thymosin-beta 4 is promoting tissue healing. BPC-157 is a peptide with 15 amino acids. It helps with the regeneration of tissue after damage.

Melanotan II is a synthetic peptide derived from melanocortin, a pituitary hormone. It helps to suppress cytokine-meditated inflammation.

FOXO4-DRI is a peptide that stimulates the removal of senescent cells. Because of this it is called a senolytic. Researchers are still investigating FOXO4-DRI in humans and for the tissue repair effect in rheumatoid arthritis patients.

The use of stem cells in RA therapy

Another biological remedy for treating RA patients is the use of mesenchymal stem cells. In 2013 rheumatoid patients received umbilical cord stem cells to study the effect of stem cells. The clinical trial consisted of 172 patients. In the trial disease modifying anti-rheumatic drugs plus placebo were compared to disease modifying anti-rheumatic drugs plus umbilical cord stem cells (treatment group). In the treatment group inflammatory cytokines were reduced and regulatory T cells were increased. Improvement was assessed with objective clinical measures and blood tests. The improvement lasted between 3 and 6 months.

Exosome therapy from mesenchymal stem cells 

Many of the effects of stem cells are explainable by so-called exosomes. They are cell particles shed by stem cells. They contain signalling proteins (integrins), messenger RNA and many other healing substances. The bioactive effects are very diverse. Exosomes are bactericidal, antifungal, stimulate angiogenesis and stimulate tissue regeneration. They are also anti-apoptosis, anti-tumoral, anti-fibrosis, stimulate immunomodulation and cause chemoattraction.

What does that mean clinically? Exosomes suppress the release of inflammatory cytokines. Anti-inflammatory cytokines (like transforming growth factor beta or TGF-beta) are increased. Exosomes reduce the Th17 cells (T helper cells that produce the inflammatory cytokine IL-17). They also promote osteochondral regeneration, which is important for joint healing in the treatment of RA patients.

Treatment of RA using the integrative and regenerative medicine approach

  1. The physician assesses all affected joints and orders blood tests to check the inflammatory status.
  2. Identify the triggers that perpetuate the RA disease. Typically there are gut dysbiosis issues that need treatment. Sleep hygiene and stress issues require modification.
  3. Assess the need for disease modifying anti-rheumatic drugs (DMARDs); these are drugs like methotrexate, sulfosalazine and others.
  4. Peptide protocol: BPC-157: 300 micrograms once or twice daily IV; Thymosin alpha: 300 micrograms once or twice daily IV; Thymosin beta: 100 to 300 micrograms once daily IV, limit to 3-month cycle.
  5. Mesenchymal stem cell therapy and exosomes.
Rheumatoid Arthritis Treatment by Regenerative Medicine

Rheumatoid Arthritis Treatment by Regenerative Medicine

Conclusion

Rheumatoid arthritis is a common autoimmune disease, which leaves the patient disabled, if she receives no treatment for it. Conventional rheumatologist protocols treat the inflammation with various drugs, but they cause a lot of side effects.

There is an emergence of regenerative therapies that may be able to help treat the inflammation of the rheumatoid arthritis patient with less side effects. At the same time these treatments can also help to repair the damaged tissues. There is a great need for more clinical studies. Current human data are limited. Safe options to treat RA patients are mesenchymal stem cell therapy, exosome treatment and peptide therapies. The approach of the physician depends on the clinical stage the patient is in. It is common sense that early diagnosis and treatment will have better results. Also, an integrative approach has the best chance to help the patient with the least side-effects.

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