Stem Cell Therapy for Ankylosing Spondylitis
Ankylosing spondylitis is a chronic, inflammatory arthritis and autoimmune disease. It mainly affects joints in the spine and the sacroilium in the pelvis and can cause eventual fusion of the spine. Approximately 90% of AS patients express the HLA-B27 genotype, meaning that there is a strong genetic association. However, only 5% of individuals with the HLA-B27 genotype contract the disease. (TNF α) and IL-1, two cytokines, (chemicals produced in our body that control our levels of inflammation) are implicated in ankylosing spondylitis. Both of these cytokines have been shown to be influenced by stem cell therapies.
The typical patient is a young male, aged 20–40, when symptoms of the disease first appear, with chronic pain and stiffness in the lower part of the spine or sometimes the entire spine, often with pain referred to one or other buttock or the back of the thigh, from the sacroiliac joint.
Men are affected more than women by a ratio about of 3:1 with the disease usually taking a more painful course in men than women. In 40% of cases, ankylosing spondylitis is associated with an inflammation of the eye iridocyclitis and uveitis), causing redness, eye pain, vision loss, floaters and photophobia. This is thought to be due to the association that these two conditions have with inheritance of HLA-B27. Another common symptom is generalized fatigue and sometimes nausea. Less commonly aortitis, apical lung fibrosis and ectasia of the sacral nerve root sheaths may occur.
Ankylosing spondylitis is one of a cluster of conditions known as seronegative spondyloarthropathies, in which the characteristic pathological lesion is an inflammation of the enthesis (the insertion of tensile connective tissue into bone).
AS can range from mild to progressively debilitating and from medically controlled to refractive. Some patients experience times of active inflammation followed by times of remission, while others never have remission and note acute inflammation and pain. Pain is often severe at rest, but improves with physical activity. However, the levels of inflammation and pain vary in intensity regardless of rest and movement, for some. A number of patients experience fusion of their spine resulting in severe rigidity with lack of normal movement.When this occurs it’s a condition known as bamboo spine.
Organs are commonly affected by the AS process include the heart, lungs, eyes, colon, and kidneys. Additional complications are aortic regurgitation, Achilles tendinitis, AV node block and amyloidosis. Owing to lung fibrosis, chest X-rays may show apical fibrosis while pulmonary function testing may reveal a restrictive lung defect.
No cure is known for AS, although treatments and medications are available to reduce symptoms and pain. Physical therapy and exercise, along with medication, are at the heart of therapy for ankylosing spondylitis. Physiotherapy and physical exercises are preceded by medical treatment in order to reduce the inflammation and pain, and are commonly followed by a physician. This way the movements will help in diminishing pain and stiffness, while exercise in an active inflammatory state would just make the pain worse. Normal occupations may be precluded by the symptoms of the
Medications There are four major types of medications used to treat ankylosing spondylitis; anti-inflamatant, pain medications, biological modifiers and immunosuppressant’s.
All the classes of medications have both along list of potential adverse events associated with their long term use and carry a significant risk for other damage to the body. Although they reduce the pain and in some cases the damage to the joints they remain only a palliative approach, at best.
TNFα blockers also referred to as biologics, such as Enbrel®, Remicade® or Humira®, have been shown to be the most promising drug treatment, slowing the progress of AS in the majority of clinical cases. Many patients receive a significant reduction, though not elimination, of their inflammation and pain. They have also been shown to be highly effective in treating not only the arthritis of the joints but also the spinal arthritis associated with AS.
A major drawback for TNGa medications includes the high cost and the significant fact that these drugs greatly increase the risk of infections. In the case of recurrent infections, including recurrent sore throats, drug therapy may need to be suspended, because of the immunosuppression. Patients taking the TNF medications are advised to limit their exposure to others who are ill, regardless of the cause such as, viral (such as a cold or influenza) bacterial or fungal infections.
Physical therapy: Physiotherapy, has shown to be of benefit to AS patients when the correct methods and levels of intensity are used. Swimming, is a preferred exercise since it involves all muscles and joints in a low-impact, non-weight bearing environment. Slow movement muscle stretching exercises, including stretching yoga, , tai chi, and Pilates, if instructed by a qualified individual, may be an excellent method of maintaining some joint flexibility.
The use of stem cell therapies to treat autoimmune processes has been available for greater than 10 years. There is a significant amount of published data with a number of approches showing responses, in a majority of patients.For a substantial list of publications, >100 related to autoimmune functions and stem cells, please see the physicians reference page.
The key influencing factors appear to be the changes that occur in restoring a more balanced immune function, along with the decrease in inflammation following stem cell therapy. There is a measurable change in the expression of cytokines, chemicals that determine the level of inflammation present along with a host of other functions.
Autologous Stem-Cell Transplant Phases :
After a review of your medical records and discussions with medical staff, a protocol is designed especially for you. Specifics of your condition are addressed along with any special needs. It may be similar to the one illustrated below:
At the clinic you will be examined by our physicians. Information including any risks and expectations concerning your treatment, plus answers to any questions you may have will be addressed. A blood draw, to determine cell counts and other chemistries will be collected and cell expansion medication may be administered. Then you will return to your hotel for a restful day or a good nights sleep.
At the clinic our physician/s will review the laboratory results, determine if the cell count is within range, and discuss the response to the stimulation. They may or may not provide additional cell expansion medications and may add adjunctive treatments. The levels of your response will determine if you would return to the hotel, with little restriction on your activities, or possibly go forward with harvesting and processing your cells.
If the cell count and viability is appropriate for harvest either a bone marrow or adipose collection will be utilized. We typically use local anesthetics for adults and general anesthesia for youngsters. The entire procedure normally takes less than 30 minutes. Although some pain is felt when the needle is inserted, most patients do not find the bone marrow or adipose collection procedure particularly painful.
We recently placed a number of videos on our website interviewing our patient’s who discuss the procedure and their lack of discomfort.
After the collection you may return to the hotel, with some restrictions. The bone marrow or adipose collected is processed in our contract State-Of-Art laboratory by trained staff, under the supervision of the lab physician.
As an alternative to the above, cord blood may be used based on the patient’s individual medical condition and options.
At the clinic or at the hospital you will be treated by IV infusion and/or a lumbar puncture, which injects the stem cells into the cerebrospinal fluid. This route transports the cells into the spinal canal and the brain directly influencing the nervous systems, thereby eliminating the brain/blood barrier. If a lumbar puncture is performed, the patient will be required to restrict their activities and potentially spend the day in the hospital or at their hotel.
At the clinic or hospital the patient will receive a post-treatment examination and evaluation prior to their release. Additional therapy and treatments may also be utilized to maximize the placement and activities of the procedure.
Day 6: Optionally there may be the use of additional ancillary therapies to enhance the procedure.
What makes our treatment different ?
Our approach includes stimulation, prior to collection, processing and expansion of the cell along with the use of growth factors, together with an integrated medical approach. This maximizes the growth and implantation potentials yielding optimized potentials of making changes in your disease.
Our staff physicians are all board certified, in their field with years of experience. Your team includes both primary and ancillary care professionals devoted to maximizing your benefits from the procedures. We enroll you in an open registry to track your changes independently, for up to 20 years.
As our patient we also keep you abreast of the newest developments in stem cell research. This is an ongoing relationship to maintain and enhance your health.
Our promise is to provide you with travel and lodging support, access to bilingual staff members throughout the entire process and most importantly the best medical care possible.
References and Articles:
2. Jiménez-Balderas FJ, Mintz G. (1993).”Ankylosing spondylitis: clinical course in women and men”. J Rheumatol 20 (12): 2069–72.3. Porter, Robert; Beers, Mark H.; Berkow, Robert (2006).
3.The Merck manual of diagnosis and therapy. Rahway, NJ: Merck ResearchLaboratories. pp. 290. ISBN 0-911910-18-2.4. “Arthritis Research Campaign –
4.Ankylosing Spondylitis Case History”. Arthritis Research Campaign.
2009. . Retrieved
2009-08-25.5. Reveille JD (2006).
5.”Major histocompatibility genes and ankylosing spondylitis”. Best Practice & Research Clinical Rheumatology 20 (3): 601–609. doi:10.1016/j.berh.2006.03.004.
PMID 16777585.6. Alpert, Joseph S. (2006). The AHA
Clinical Cardiac Consult.
6.Lippincott Williams & Wilkins. ISBN 0781764904.7. Toivanen A, Möttönen T. (1998).
“Ankylosing spondylitis: current
approaches to treatment.”. BioDrugs 10 (3): 193–200.
doi:10.2165/00063030-199810030-00003. PMID 18020595.8.
7.Williams RO, Paleolog E, Feldmann
M. (2007). “Cytokine inhibitors
in rheumatoid arthritis and other autoimmune diseases.”. Curr Opin
Pharmacol 7 (4): 412–7. doi:10.1016/j.coph.2007.06.001.
Oxford Journals Medicine Rheumatology Volume 39, Issue 5 Pp. 563-564.
Autologous stem cell transplantation in a lymphoma patient with a long history of ankylosing spondylitis
E. Jantunen, et al Department of Medicine, Kuopio University Hospital, Kuopio, Finland Accepted November 19, 1999.
“This report suggests that complete clinical remission is possible in active AS following chemotherapy for lymphoma including ASCT.”
Best Pract Res Clin Rheumatol.2008 Apr;22(2):269-84.
Multipotent mesenchymal stromal cells in articular diseases
“Recent studies have provided new perspectives for cartilage engineering using multipotent mesenchymal stromal cells (MSC). This chapter focuses on the potential of MSC to repair cartilage, with an emphasis on the factors that are known to be required in inducing chondrogenesis and on their immunosuppressive potential”
Immunosuppressive properties of mesenchymal stem cells: advances and applications.
Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, such as bone marrow, skeletal muscle, dental pulp, bone, umbilical cord and adipose tissue. MSCs are used in regenerative medicine mainly based on their capacity to differentiate into specific cell types and also as bioreactors of soluble factors that will promote tissue regeneration from the damaged tissue cellular progenitors. In addition to these regenerative properties, MSCs hold an immunoregulatory capacity, and elicit immunosuppressive effects in a number of situations. Not only are they immunoprivileged cells, due to the low expression of class II Major Histocompatibilty Complex (MHC-II) and costimulatory molecules in their cell surface, but they also interfere with different pathways of the immune response by means of direct cell-to-cell interactions and soluble factor secretion. In vitro, MSCs inhibit cell proliferation of T cells, B-cells, natural killer cells (NK) and dendritic cells (DC), producing what is known as division arrest anergy. Moreover, MSCs can stop a variety of immune cell functions: cytokine secretion and cytotoxicity of T and NK cells; B cell maturation and antibody secretion; DC maturation and activation; as well as antigen presentation. It is thought that MSCs need to be activated to exert their immunomodulation skills. In this scenario, an inflammatory environment seems to be necessary to promote their effect and some inflammation-related molecules such as tumor necrosis factor-α and interferon-γ might be implicated. It has been observed that MSCs recruit T-regulatory lymphocytes (Tregs) to both lymphoid organs and graft. There is great controversy concerning the mechanisms and molecules involved in the immunosuppressive effect of MSCs. Prostaglandin E2, transforming growth factor-β, interleukins- 6 and 10, human leukocyte antigen-G5, matrix metalloproteinases, indoleamine-2,3-dioxygenase and nitric oxide are all candidates under investigation. In vivo studies have shown many discrepancies regarding the immunomodulatory properties of MSCs. These studies have been designed to test the efficacy of MSC therapy in two different immune settings: the prevention or treatment of allograft rejection episodes, and the ability to suppress abnormal immune response in autoimmune and inflammatory diseases. Preclinical studies have been conducted in rodents, rabbits and baboon monkeys among others for bone marrow, skin, heart, and corneal transplantation, graft versus host disease, hepatic and renal failure, lung injury, multiple sclerosis, rheumatoid arthritis, diabetes and lupus diseases. Preliminary results from some of these studies have led to human clinical trials that are currently being carried out. These include treatment of autoimmune diseases such as Crohn’s disease, ulcerative colitis, multiple sclerosis and type 1 diabetes mellitus; prevention of allograft rejection and enhancement of the survival of bone marrow and kidney grafts; and treatment of resistant graft versus host disease. We will try to shed light on all these studies, and analyze why the results are so contradictory.
Stem cells in the treatment of inflammatory arthritis
Alan Tyndall, Jacob M. van Laar Best Practice & Research Clinical Rheumatology August 2010 (Vol. 24, Issue 4, Pages 565-574)
“Autologous haematopoietic stem cell transplantation in patients with rheumatoid arthritis (RA) resulted in a positive short-term outcome clinically with low treatment-related toxicity. Mesenchymal stem cells (MSCs), derived from several sources including bone marrow and adipose tissue, are being tested as tissue-regenerative and immunomodulating agents in many autoimmune diseases and animal models of inflammatory arthritis have been positive.”
Best Pract Res Clin Rheumatol. 2001Dec:15(5):711-26
Stem cells in the aetiopathogenesis and therapy of rheumatic disease
John Moore, MB.BS, FRACP, FRCPA
“ Given the morbidity and increased mortality in some patients with severe autoimmune diseases and the increasing safety of autologous haemopoietic stem cell transplantation (HSCT), pilot studies have been conducted using HSCT in rheumatic diseases. It is still unclear whether an autologous graft will cure these diseases but significant remissions have been obtained which have provided important data for the design of
randomized trials of HSCT versus more conventional therapy.”