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Stem Cell Therapy: Personalized Healing for Arthritis Patients
Free Download: Stem Cell Therapy for Rheumatoid Arthritis
Disclaimer:
The information provided by R3 Stem Cell is for educational purposes and is not a substitute for professional medical advice, diagnosis, or treatment. Individual results may vary and are not guaranteed. The FDA considers stem cell therapy experimental at this point.
Any claims made on this website refer to procedures performed OUTSIDE of the USA. R3 Stem Cell has clinics in Mexico, Philippines, South Africa, Turkey, India, Pakistan.
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Every day, R3 Stem Cell receives inquiries worldwide from individuals asking if stem cell therapy can help with Rheumatoid Arthritis (RA). Spoiler alert: It can help a lot! In this guide, we’ll go through the basics of how stem cells and exosomes work for RA, the latest research, and what to expect with a regenerative procedure.
Conventional treatments for RA are often not able to successfully promote remission significantly. For those who desire reduced pain along with less swelling and improved energy and functional abilities, failure with conventional treatments is disappointing and occurs all too often.
Stem cell therapy for RA is turning out to be an excellent opportunity for individuals to achieve meaningful long term results. Let’s dig in!
If you have RA, call (844) GET-STEM to ask about treatment at R3 Stem Cell.
Rheumatoid arthritis (RA) is a chronic systemic disease that causes damage to joints, connective tissues, muscle, tendons, and fibrous tissue, and, as a result, has a major impact on society. According to the evidence, the prevalence of rheumatic diseases such as RA has increased in the last decades, with a global prevalence of 460 per 100,000 population between 1980 and 2019. Women are affected three times more than men, with a mean age of 55 years old.
The advanced form of the disease is characterized by severe and debilitating chronic pain that compromises patients’ quality of life. Inadequate management further results in disease progression, which ultimately leads to joint erosion, destruction and deformities.
Previously, more than 50% of RA patients were disabled, incapable of serving on a full-time work basis, and were subject to increased mortality. However, the 21st Century has led to a better understanding of disease pathophysiology and remarkable progress in the treatment of RA. This has resulted in the development of more efficient treatment approaches with the improvement of the disease activity control, the degree of pain and joint damage. Nevertheless, up to half of patients fail current conventional treatment options.
Rheumatoid arthritis is an autoimmune disease, and it is associated with intense, chronic inflammation.
There is growing evidence that RA involves chronic inflammation resulting from innate and adaptive immune system dysfunction, including immune responses to autoantigens, abnormalities in the cytokine signaling network, and complement activation by immune complexes.
This disease initially affects the synovial joints (see figure below) and later progresses to the skin, eyes, heart, kidneys, and lungs. Ultimately, the patient suffers from joint failure characterized by cartilage damage and severely weakened tendons and ligaments.
Essentially, one forms autoantibodies versus synovial tissue in joints. This is very different from osteoarthritis (wear and tear). Some of the immune cells responsible for inflammation are monocytes, macrophages, T lymphocytes, and B cells. The synovial membrane and cartilage undergo significant inflammation, causing hyperplastic synovium and cartilage destruction that eventually lead to bone erosion, significant swelling, deformity and pain.
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The main goal in RA treatment is to achieve clinical remission or to reduce disease progression by inhibiting joint inflammation. Currently available conventional treatment methods include synthetic and biologic DMARDs (disease modifying anti-rheumatic drugs) along with glucocorticoids (GCs).
DMARDs are the mainstay of RA therapy, which include heterogeneous drugs that inhibit disease progression and control symptoms. About 30-50% of patients are unresponsive to conventional DMARDs. If a 2-6 month treatment with methotrexate mono or combined therapy is inadequate, additional DMARDs should be added.
NSAIDs are commonly used as adjuvants to DMARDS. They are applied to decrease pain and inflammation during RA, however NSAIDs are not able to reduce bone and cartilage destruction. Previously, NSAIDs were considered as first-line drugs, however low effectiveness in preventing damage progression and side effects at high doses such as nausea, abdominal pain, ulcers and gastrointestinal bleeding, limited the implementation of these drugs.
Among the above-mentioned conventional treatments, DMARDs demonstrated a high potential to reduce disease symptoms and prevent disease progression in patients with RA, however, they constitute high financial costs and exhibit serious side effects. Additionally, despite significant pain reduction reported in numerous randomized controlled trials, many patients still experience clinically meaningful levels of remaining pain despite the treatment, and continue to be intolerant or resistant to these therapies
RA patients require long-term treatment, and according to the evidence, currently available drugs have limited efficacy; in fact, some patients do not achieve remission and disease control despite being treated with multiple conventional disease-modifying antirheumatic drugs (DMARDs) alone and in combination. Consequently, persistent inflammation leads to progressive joint and end-organ damage; therefore, the prognosis of these patients is poor and evidence the need for new therapeutic options.
Approximately 30% of RA patients may not respond to treatment or experience severe side effects, including bone marrow suppression, blood, liver, and/or kidney dysfunction, and infection. Moreover, DMARDs are contraindicated for RA patients with compromised immunity due to the heightened risk of opportunistic infections.
Surgery is the final treatment approach for RA therapy in cases when the nonsurgical methods are not sufficiently effective, which are becoming less frequent. Nowadays, various types of surgery are being applied, among them are tenosynovectomy, radiosynovectomy, arthroscopy, osteotomy and joint replacement. The final goal of surgical management is to relieve pain and restore joint function.
Call (844) GET-STEM and ask how regenerative care may fit your health goals.
Since the 21st Century began, multiple small and large clinical trials have evaluated mesenchymal stem cells for both safety and effectiveness in rheumatoid arthritis.
In 2013, a group of researchers performed a phase 1/2 clinical trial to evaluate the safety and efficacy of IV injection of allogeneic umbilical cord mesenchymal stem cells in patients with active RA. In the study, 172 RA patients who failed to respond to conventional treatment were enrolled. The control group of patients received culture medium without UC MSCs.
The experimental group of patients received a single dose of 4 × 107 UC MSCs (40 million). All groups of patients received DMARD treatment. The results of the clinical study showed that UC MSCs treatment did not induce any adverse effects and resulted in the following clinical improvements: a moderate reduction in inflammatory cytokines and chemokines, an increase in percentage of Tregs in peripheral blood and upregulation of IL-4-producing Th2 cells.
In addition, a significant disease remission was observed by the ACR improvement criteria, the DAS28 score and the Health Assessment Questionnaire (HAQ), which were maintained for 3-6 months without repeated IV injection of UC MSCs. Moreover, an additional clinical study demonstrated that UC MSCs treatment can exert long-term beneficial effects in RA patients for up to 3 years. Thus, this clinical trial showed that IV administration of allogeneic umbilical cord mesenchymal stem cells in combination with DMARDs was safe and effective in ameliorating disease activity in refractory RA patients, compared to the control group that received culture medium without UC MSCs.
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Figure 7 A: 33-year female, with 4 years of illness, (A) difficulty in clenching, swelling and pain, morning stiffness, (B) Alone UC-MSC cells treatment | vesicle, the symptoms improved significantly.
Overall, our study demonstrated the long-term safety and efficacy of UC-MSC therapy in RA patients. The therapeutic effects of UC-MSC can be maintained for 3 years, with stable clinical outcomes, which significantly improve RA patients’ quality of life.
Above are some photos from the study of patient outcomes.
From 2011 to 2013, 30 RA patients were recruited for a randomized, triple-blind placebo-controlled phase 1/2 clinical trial to study the safety and tolerability of intra-articular injection of autologous bone marrow mesenchymal stem cells in RA patients. The results published in 2018 showed that MSCs administration does not exert any adverse effects in RA patients. Moreover, it was revealed that in comparison to the patients in the placebo group, patients who received intra-articular injection of BM MSCs demonstrated superior clinical results according to the Western Ontario and McMaster Universities Arthritis Index (WOMAC), visual analogue scale (VAS), time to jelling and painfree walking distance up to 12 months. on these data, the authors have suggested that intra-articular knee injection of BM MSCs is generally safe and well tolerated in RA patients.
Recently, Ghoryani and colleagues completed a successful clinical trial on the effects of IV administration of autologous mesenchymal stem cells on the various immunological, clinical and para-clinical indicators that are associated with the pathogenesis of RA in patients with refractory RA. They showed that a single IV injection of 1 × 106 BM MSCs/kg resulted in a significant decrease in Th17 cell number, disease activity score 28-erythrocyte sedimentation rate (DAS28-ESR) and VAS at 12 months after MSC therapy. Taken together, these clinical data suggested that autologous BM MSCs can significantly ameliorate the severity and activity of refractory RA.
Is stem cell therapy safe?
After a decade of performing over 24,000 stem cell procedures worldwide, R3 knows that the regenerative procedures are safe. The quality control employed during the stem cell production is second to none, and the side effects R3 sees are usually mild to moderate and temporary.
They may include itching, dizziness, lightheadedness, low grade fever, chills, headache, nausea. These are typically temporary. If a patient has an allergic reaction to the multivitamin or a preservative, all of R3’s Centers have the medications to resolve it quickly.
One of the questions we get asked a lot is, “Will the stem cells get rejected?” The answer is NO.
MSCs do not express major histocompatibility complex (MHC) antigens of the class II subtype and contain low levels of MHC molecules of the class I subtype. MSCs also lack the co-stimulatory molecules essential for immune detection, including CD40, CD80, and CD86.
Therefore, MSCs generally have low immunogenicity and can avoid immune rejection by the recipient, which serves as the foundation for their successful application without needing to match the donor to the recipient. Scientists call this being “immunologically privileged.”
Another question often asked is “Is there a chance of a tumor forming?” Current research has concluded that the answer is NO. The mesenchymal stem cells and exosomes used during treatment have never been shown to have tumor forming potential. In fact, they have been shown to be anti-tumor forming.
How do the Stem Cells and Exosomes Act in the Body?
Stem cells and exosomes act in the body through several mechanisms. They do NOT become part of a patient’s DNA, which means they do not engraft into the person’s existing cells.
They act through:
Angiogenesis
Provokes formation of new blood vessels.
Reduce inflammation
RA is associated with significant inflammation, and the regenerative biologics reduce it nicely.
Immune system modulation
the stem cells and exosomes modulate the immune system very differently than steroids. Instead of blankety suppressing the immune system, the regenerative biologics tamp down the harmful processes while amping up the beneficial ones. This includes ramping up production of several helpful growth factors and cytokines, while tamping down harmful ones.
Cellular signaling
the biologics are able to perform "cell-to-cell" communication. This promotes recipient cells to proliferate their growth factor production, protein production and regenerate nerve tissues that are damaged.
Prevent cell death
most cells have a timed death, where they are only allowed to live a certain length of time. This is called apoptosis. The regenerative biologics allow normally functioning cells (i.e. neuron cells) to live longer, and spare them from the pre-programmed death.
Preventing scar tissue
Once that scar tissue forms, it becomes nonfunctional. Stem Cells and exosomes are great at preventing scar tissue (anti-fibrosis).
Stem Cells can also release a huge variety of molecules into the extracellular environment. These molecules, which include extracellular vesicles (exosomes), lipids, free nucleic acids, and soluble proteins, exert crucial roles in repairing damaged tissue. Along with offering stem cells for treatment of RA, R3 Stem Cell includes stem cell exosomes, which are a type of extracellular vesicle participating in extensive cell-to-cell communication for ovarian tissue repair and regeneration.
The stem cells administered by R3 are not the ones that become a patient’s new follicle. The administered mesenchymal stem cells are not specifically designed to replace damaged and lost follicles, but rather coordinate and enhance an ovarian repair response by one’s own mechanisms.
Ask about therapy options for joint pain due to RA: (844) GET-STEM.
Where do the stem cells and exosomes come from?
R3 Stem Cell’s regenerative biologics originate from umbilical cord tissue that has been donated after a scheduled c-section. No baby (or mother) is harmed during the C-section procedure. The umbilical cord tissue is normally discarded, but if the mother passes screening test then the umbilical cord is immediately sent to the lab.
The lab carefully processes the umbilical cord to generate large amounts of stem cells and exosomes that are of the highest quality possible. The lab team consists of multiple PhD’s working in ISO Certified, cGMP compliant clean rooms to ensure quality assurance that exceeds USA FDA standards. The proprietary production process combines the highest potency, safety and affordability for providers to confidently offer exposure procedures.
Millions of dollars have been invested in the pharmaceutical grade production of the biologics including first rate clean rooms, bioreactors, nano-particle tracking analyzers, cytometers, PCR, tangential flow machines and real-time environmental monitoring. The quality assurance testing complies with screening and testing standards consistent with the American Association of Tissue Banks, cGMP standards, FDA regulations and the highest level of any regulatory agency globally.
Ask about therapy options for joint pain due to RA: (844) GET-STEM.
R3 Stem Cell’s Centers of Excellence globally include umbilical cord stem cell derived exosomes with umbilical cord stem cells to provide enhanced results. Exosomes are lipid bound vesicles (acellular) produced by cells that contain a plethora of growth factors, cytokines, mRNA and other proteins.
They are exceptionally helpful in cell-to-cell communication, and very effective for reducing inflammation when they become ingested by their recipient cell. They act as shuttles to send nucleic acids and proteins to other cells, in this way, allowing cell-to-cell communication and transporting molecules among both close and distant cells. In general, these released proteins are important regulators of intracellular information.
Exosomes could be the mediators of many stem cell-associated therapeutic activities. Considering they are 100 times smaller than stem cells, they do not have any issues passing through the blood-brain-barrier to reach the brain from the bloodstream.
After a decade of performing over 24,000 stem cell procedures worldwide, R3 knows that the regenerative procedures are safe. The quality control employed during the stem cell production is second to none, and the side effects R3 sees are usually mild to moderate and temporary.
They may include itching, dizziness, lightheadedness, low grade fever, chills, headache, nausea. These are typically temporary. If a patient has an allergic reaction to the multivitamin or a preservative, all of R3’s Centers have the medications to resolve it quickly.
One of the questions we get asked a lot is, “Will the stem cells get rejected?” The answer is NO.
MSCs do not express major histocompatibility complex (MHC) antigens of the class II subtype and contain low levels of MHC molecules of the class I subtype. MSCs also lack the costimulatory molecules essential for immune detection, including CD40, CD80, and CD86.
Therefore, MSCs generally have low immunogenicity and can avoid immune rejection by the recipient, which serves as the foundation for their successful application without needing to match the donor to the recipient. Scientists call this being “immunologically privileged”.
Another question often asked is “Is there a chance of a tumor forming?” Once again the answer is NO. The mesenchymal stem cells and exosomes used during treatment have never been shown to have tumor forming potential. In fact, they have been shown to be anti-tumor forming.
For the past decade, R3 has been successfully treating patients with stem cell and exosome therapies with injection, infusion, intranasal, intrathecal and nebulizer procedures.
For Rheumatoid Arthritis, R3’s providers use between one and three million stem cells per kilogram (depends on patient weight). In addition, billions of stem cell exosomes and platelet rich plasma therapy (PRP) are included at no cost.
R3 Stem Cell’s RA treatment protocol includes an IV therapy combining mesenchymal stem cells and exosomes, along with a multivitamin IV as well. The RA protocols are customized to each patient’s needs.
For example, if an individual has several painful joints, R3’s providers may perform some direct injections along with the IV therapy. Safety is paramount with the biologics products being rigorously tested prior to use, and expert providers managing each treatment as if you were a family member!
Although autologous (your own) stem cells provide significant advantages, allogeneic (donor) stem cells have more advantages. First of all, autologous MSCs need a long time to culture and expand, which limits its application in treatment, while allogeneic stem cells can be obtained and expanded more quickly, thus avoiding the delay of time window.
Second, age is a factor that affects the physiological characteristics of MSCs. Studies have shown that stem cells from elderly donors have decreased proliferation and differentiation ability. This means they are less in number and less effective!
Stem cell therapy for RA may be the key step to completely changing a person's quality of life, and we want to make it affordable for as many individuals as possible. Our global volume has allowed us to keep our patient costs as low as possible.
Unfortunately, stem cell clinics in Colombia, China and Panama charge over $20,000 USD for RA treatment. How are individuals supposed to budget for that? R3 Stem Cell's fees are typically less than half that for full treatment, which also includes free exosomes, PRP and a multivitamin infusion!
For the past decade, R3 Stem Cell's Centers globally have performed over 24,000 regenerative procedures in six countries. Patient satisfaction across all conditions treated is very high, at 85%. R3 has treated hundreds of patients with varying types of peripheral neuropathy, and over a thousand patients with diabetes.
R3 combines safety, effectiveness and affordability for the therapies. Internationally, the Intellicell is used, which is culturing the most active mesenchymal stem cells to create the "smartest" stem cell in the world!
References
David Greene, MD, PhD, MBA, Founder/CEO
R3 Stem Cell offers treatments that bring patients hope and options. Hope that surgery can be avoided, and tissue injury can be repaired with patients being able to get back to desired activities.
Founder and CEO David Greene, MD, PhD, MBA writes extensively on regenerative medicine and gives many seminars worldwide on a regular basis. With over forty Centers of Excellence globally, R3 is at the forefront of regenerative therapies.
R3’s Centers have successfully performed over 25,000 regenerative procedures to date. Call today for your free consultation (844) GET-STEM!
No portion of this Document may be reproduced without the Express Written Consent of R3 Stem Cell.
This guide’s education does not constitute medical advice. The USA FDA considers stem cell therapy experimental. Any claims made in the Guide refer to procedures performed outside the USA.
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