Stem cell therapy and regenerative medicine treatments have broad indications for patients with a whole spectrum of inflammatory conditions. Inflammation refers to the biological response to stimuli that your body interprets as being potentially harmful. While after injury and in certain conditions inflammation is a normal response, inflammatory disorders that result in the immune system attacking the body's own cells or tissues may cause abnormal inflammation, which results in chronic pain, swelling, stiffness, and damage to normal tissues.
Examples of inflammatory conditions include: Pulmonary sarcoidosis, idiopathic pulmonary fibrosis, Rheumatoid Arthritis, Systemic Lupus Erythematosus (SLE), and inflammatory bowel disease (IBD). See below for more details.
Sarcoidosis is a devastating inflammatory disease affecting many organs especially the lungs and lymph nodes. Researchers at the NIH have shown that bone marrow derived mesenchymal stromal stem cells (MSCs) modulate inflammation of alveolar macrophages in patients with lung sarcoidosis (Ian Caldwell, 2020). In particular, MSCs can “reprogram” macrophages to an anti-inflammatory phenotype. When sarcoid macrophage cells were cocultures with healthy MSCs, there was a reduction of TNF alpha (pro-inflammatory) and an increase in IL-10, which is anti-inflammatory. We here at Phenicell Regenerative Institute offer both adult bone marrow stem cells as well as umbilical cord stem cells. However, we favor umbilical cord stem cells for patients over 55 years of age.
Idiopathic Pulmonary Fibrosis
Idiopathic pulmonary fibrosis (IPF) is a type of chronic scarring lung disease characterized by a progressive and irreversible decline in lung function. The cause is unknown. Symptoms typically include gradual onset of shortness of breath and a dry cough. Other changes may include dome shaped finger and toenails called nail clubbing. Complications may include pulmonary hypertension, heart failure, pneumonia, or pulmonary embolism. Risk factors include cigarette smoking, certain viral infections, and a positive family history. The underlying mechanism involves scarring of the lungs, hence the name, fibrosis. Diagnosis is by exclusion and requires ruling out other potential causes. It may be supported by a CT scan. It is a type of interstitial lung disease (ILD). People often benefit from pulmonary rehabilitation and supplemental oxygen. Certain medications like pirfenidone or nintedanib may slow the progression of the disease. Lung transplantation may also be an option. The overall world prevalence is about 5 million people. The disease is newly diagnosed in about 12 per 100,000 people per year. Patients are usually in their 60s and 70s. Average life expectancy following diagnosis is about four years. Phase I clinical trials using MSCs from bone marrow (47), placenta (48) and adipose tissue (49) in the treatment of idiopathic pulmonary fibrosis have demonstrated a safe profile without evidence of worsening fibrosis due to the therapy. We here at Phenicell Regenerative Institute offer both adult bone marrow stem cells as well as umbilical cord stem cells. However, we favor umbilical cord stem cells for patients over 55 years of age.
Systemic Lupus Erythematosus (SLE) & Nephritis
Systemic lupus erythematosus (SLE) is a polymorphic, multisystemic autoimmune disease that causes multiorgan damage in which cellular communication occurs through the involvement of autoantibodies directed against autoantigen production. There has been a lot of interest in mesenchymal stem cells to manage SLE due to stem cells protective and immunomodulatory abilities. Mesenchymal stem cells can be obtained from bone marrow, adipose tissue, and umbilical cord tissue. They are recognized as a promising tool. Zhou et al, in 2020 published a comprehensive review of the medical literature on the clinical efficacy and safety of mesenchymal stem cells for SLE and reviewed 386 scientific publications. Of these publications, there were 4 randomized controlled studies. The results of two particular studies which used intravenous infusions of umbilical cord derived mesenchymal stem cells showed lower proteinuria, than the control groups at 3 months, and 6 months. Stem cell treated patients also displayed a lower SLE disease activity index (SLEDAI) and less adverse events (Yang, 2014) (Tang, 2016). Mesenchymal stem cells derived from umbilical cord blood also helped lupus nephritis (Tang, 2016). Here at Phenicell Regenerative Institute, we are honored to treat and study patients with SLE using this new and exciting treatment.
Inflammatory Bowel Syndrome
Inflammatory bowel disease which encompasses Ulcerative Colitis and Chron’s disease is thought to occur as a result of inappropriate response of the host immune system to intestinal microbes. Thus, current management strategies consist of targeting inflammation and suppressing the immune system with medications like corticosteroids and monoclonal antibodies against cytokine, Tumor Necrosis Factor alpha (infliximab). Unfortunately, approximately 60% of these patients do not achieve medical remission, even with combination therapy; many have side effects from the medications such as serious infections or neurological disorders or malignancies (Dave, M, et al, 2015). Thus, there is a need for novel therapies for IBD and stem cells have gotten much interest in the last few years. Multiple studies suggest that the immunomodulatory effects of stem cells may reduce inflammation and tissue damage in patients with IBD. Liang et al, in 2012 showed clinical improvement is all seven or seven patients with refractory IBD after treating patient with intravenous infusion of mesenchymal stem cells. Phenicell Regenerative Institute is committed to treating and studying these patients in an attempt to solve these problems.
Traditional medications to treat rheumatoid arthritis fall into 4 classes. First, we have glucocorticoids (GCs), then nonsteroidal anti-inflammatory drugs (NSAIDS). These first two categories of medications are used to predominantly control the pain and inflammation, but have significant side effects like elevating serum glucose the GCs and gastrointestinal and renal damage with NSAIDS. A third category of drugs for RA are called disease-modifying antirheumatic drugs (DMARDs) and lastly, biological therapies used to target and inhibit specific molecules on the immune and inflammatory responses.DMARDs used for RA therapy are:
- Hydroxycholorquine (Plaquenil)
- Methotrexate (Otrexup™, Rasuvo®, Rheumatrex® and Trexall™)
- Leflunomide (Arava)
- Sulfasalazine (Azulfidine)
- Chimeric antiCD20 monoclonal antibody, Rituximab (Rituxan)
- Inhibitor of TNF alpha (such as etanercept, infliximab and adalimumab) ENBREL, Remicade and Humira, respectively
- Recombinant inhibitor of Interlukin-1 (such as anakinra, brand name Kineret)
- Costimulation blocker, abatacept. (Orencia)
- New inhibitors of TNF alpha
- JAK inhibitors
- Anti-interleukin-6 receptor monoclonal antibodies
- Antibodies against important molecules of functional B Cells.
All of the above medications are expensive and more importantly, have significant side effects. That is why at Phenicell Regenerative Institute, we prefer to use more natural remedies, such as stem cells or pure exosomes therapy for patients with rheumatoid arthritis. Although these treatments are effective and safe and have been used all over the world, they are still NOT FDA approved yet (Wang, L. et al, 2019). At our institute we offer intravenous autologous BMAC or intravenous adult human umbilical cord blood mesenchymal cell treatment. We will soon be participating in IRB approved clinical research trials on patients with autoimmune and inflammatory conditions, to add to our IRB approved spinal cord injury research protocol.Exosome Therapy
At Cedar, we also offer the latest regenerative medicine treatment called exosomes for our rheumatoid arthritis patients. Exosomes are nano-sized mammalian extracellular particles with essential properties to regulate biological processes and cellular signaling. There has been much interest in exosomes and their genetic content they transport in various diseasesin particular, autoimmune disease. Exosomes have diagnostic, prognostic and therapeutic implications of in rheumatoid arthritis (Tavasolian, et al, 2020). Zheng et al, 2020, recently studied BM derived mesenchymal stem cells secreting exosomal miRNA-192-5p and showed that this exosome can delay the inflammatory response in rheumatoid arthritis in rat model. Chen, et al, 2020, showed how exosomes carrying miRNA-486-5p help to promotes osteoblast differentiation in a mouse model of rheumatoid arthritis.
Fibromyalgia is a Medical condition characterized by chronic widespread pain and a heightened pain response to pressure. The term "fibromyalgia" is from Latin fibro-, meaning "fibrous tissues", Greek myo-, "muscle", and Greek algos, "pain"; thus Painful muscles and connective tissues.
Fibromyalgia is common and is estimated to affect 2–8% of the population. Women are affected twice as often as men. Rates appear similar in different areas of world and among different cultures. Fibromyalgia first defined in 1990. There exists some controversy about classification, diagnosis, and treatment of fibromyalgia.
Clinical Presentation: Patients present to the doctor with Pain, tiredness to a degree that affects normal activities, sleep problems, troubles with memory, restless legs syndrome, bowel or bladder problems, numbness and tingling and sensitivity to noise, lights or temperature. FM is frequently associated with depression, anxiety, and posttraumatic stress disorder. Other types of chronic pain are also frequently present. Best way to make the Diagnosis is by doing a history and physical exam, Labs (like CRP, Sed rate), Imaging Studies like Cervical MRI and EMG studies. The differential diagnosis for FM is long. Differential diagnosis means what else could it be. This could be: Systemic Lupus Erythematosus, Sjögren syndrome, non-celiac gluten sensitivity, Hypothyroidism, ankylosing spondylitis, polymyalgia rheumatica, rheumatoid arthritis, psoriatic-related polyenthesitis, hepatitis C, peripheral neuropathies, nerve compression syndrome (carpal tunnel syndrome), multiple sclerosis and myasthenia gravis.
Treatment of fibromyalgia can be difficult. Conventional Treatment options include: getting enough sleep, exercising regularly, and eating a healthy diet, Cognitive behavioral therapy (CBT) may be helpful. Dietary supplements such as vitamin D can help. Sometime Medications such as Cymbalta (duloxetine) or Lyrica (pregabalin) or Savella milnacipran are helpful. Rarely weak opioid pain medication may be reasonable if other medications are not effective. Here at Phenicell, we offer several regenerative medicine treatment options.
References: 1.) Chinn S, Caldwell W, Gritsenko K.: Fibromyalgia Pathogenesis and Treatment Options Update. Curr Pain Headache Rep. 2016 Apr;20(4):25. 2.) Illescas-Montes, R.; Costela-Ruiz, V.J.; MelguizoARodríguez, L.et al: Application of Salivary Biomarkers in the Diagnosis of Fibromyalgia. Diagnostics 2021, 11, 63.