Osteoarthritis and Stem Cell Therapy
Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease.
The chronic disease Osteoarthritis (OA) is characterized by the breakdown of cartilage. As the cartilage in the joints deteriorate, there is less space between the two adjacent bones and eventually as the condition advances, bones begin to rub against one another when moving the joint. This condition can cause pain, swelling, stiffness, and the loss of joint range of motion. As a result of osteoarthritis, patients become less active.
The normal activities of daily living such as walking, sitting, bending, and any sports activity that require motion of the joint become more a more difficult. Osteoarthritis of the joints can also be associated with other soft tissue injuries including tendinitis, bursitis, labral tear meniscus issues, and so forth. Osteoarthritis is considered primary if it is associated with normal process of aging. Osteoarthritis is considered secondary if it follows an injury. Osteoarthritis most often occurs in shoulders, knees, hips, hands, and feet.
Stages of Osteoarthritis
Signs of Osteoarthritis
Early signs of osteoarthritis include morning stiffness, joint pain, and minor swelling. As the disease progresses, clicking, grinding, locking, giving way, and reduction in range of motion become more prevalent. In general, moving an arthritic joint results in pain. In joints like hip joint and knee joint, weight bearing and walking causes pain. Combination of pain, stiffness and reduced range of motion will result in a degree of impairment and disability in individuals with osteoarthritis.
Diagnosis of Osteoarthritis
The diagnosis of osteoarthritis is based on physical examination, imaging of the targeted joint, which may include x-rays and MRIs. X-rays are helpful to assess this stage of osteoarthritis and determine the degree of joint space narrowing and asymmetry, as well as bone spurring. MRIs are more sensitive to soft tissue changes including bursitis, tendinitis, tendon tear, synovitis, ligamentous injury, meniscus tear, labral tear, and so forth. Sometimes a combination of both tests is necessary for accurate diagnosis but in many cases, X-rays are sufficient.
Treatment of Osteoarthritis (non-operative): Rehabilitation and Medical Management:
Early osteoarthritis treatment is focused on improving pain, reducing inflammation, increasing range of motion and conditioning of the appropriate muscles around the joint and weight loss. In many cases, taking over-the-counter (or prescribed) anti-inflammatories, and several weeks of physical therapy (PT) makes the pain and stiffness go away. Physical therapy exercises include strength training, range of motion exercises, aerobic exercises, neuromuscular training, and if the patient cannot tolerate land therapy, aquatic therapy can be offered. In some cases, bracing, topical medication, kinisio-taping and using the cane can be helpful.
If the pain and function does not get better with rehabilitation and medical management, injecting corticosteroid into the joint can reduce inflammation, improve pain, and increase compliance with PT and perhaps accelerate the progress in PT. Often when successful, steroid injections may need to be repeated in certain intervals to control the symptoms. Although steroid injections are commonly performed and are among recommended guidelines for treatment of osteoarthritis, one should be aware of potential complications including infection, negative impact on blood sugar level, hormonal imbalance, and negative effect on bone density. Image guided corticosteroid injection will assure delivery of the medication to appropriate target.
In the past few years, as regenerative medicine treatments have advanced, alternative treatments including PRP (Plasma Rich Platelet) and stem cell treatments have become available to patients for management of painful joints due to osteoarthritis or soft tissue injuries of the joint.
Stem Cell Therapy for Osteoarthritis:
Stem cell treatment for osteoarthritis is a new alternative way to help manage the symptoms of this chronic disease.
As new research and treatment strategies have emerged, stem cell therapy has risen in popularity for the management of degenerative joint conditions. Results of several early clinical studies of stem cell treatment for osteoarthritis have shown promising results (see end of this document for list of studies). This breakthrough in regenerative medicine shines a light of hope on those battling this degenerative disease.
When the individual is treated with stem cell therapy, we take advantage of the stem cell’s ability to differentiate into chondrocytes (cartilage cells) when injected into the arthritic joint. Improvement in the health of the cartilage within the joint results in decreased inflammation, improvement of range of motion and ultimately improvement of pain and enhanced function. If successful, it may spare patient from immediate need for surgical intervention.
Finally surgery, including joint replacement, may be a considered option for severely arthritic or injured joints.
Stem Cell Biology
In general we have 2 types of stem cells. Human embryonic stem cell (pluripotent) or adult stem cell (Multipotent- Mesenchymal). Adult stem cells have been identified in many organs and tissues. These stem cells are thought to reside in a specific area of each tissue where they remain quiescent (non-dividing) for many years until they are activated by a normal need for more cells, or by disease or tissue injury.
Embryonic stem cells are thought to have much greater developmental potential than adult stem cells. Adult stem cells may contain more DNA abnormalities—caused by sunlight, toxins, and errors in making more DNA copies during the course of a lifetime which may limit the usefulness of adult stem cells.
Autologous Stem Cell (from patient to his/herself):
Stem cell that are currently used are driven from either bone marrow (iliac crest) or adipose tissue (abdominal fat) of the individual with osteoarthritis. Both adipose driven adult stem cells, as well as bone marrow stem cells produce a large number of growth factors and other molecules including cytokines and chemokines. The growth factors assist with natural course of healing and some of the cytokines and chemokines are anti-inflammatory.
Allogenic Stem Cell (transplantation from a healthy donor to the patient):
An alternative stem cell source is allogenic foetal stem cells. Various subtypes of foetal stem cells have been described based on the tissues from which they are derived (i.e. amniotic fluid, umbilical cord, amniotic membrane and placenta of healthy mother- newborn).
The relatively easy accessibility and high proliferation rate makes foetal stem cells ideal sources for regenerative medicine. Since after the newborn is delivered, umbilical cord/ blood, placenta and amniotic fluid are discarded as medical waste, most individuals consider using these stem cell sources both acceptable and ethical. Stem cells are never acquired from the newborn body itself or before birth.
What is a Stem Cell Therapy Procedure Like?
The treatment with stem cell is relatively simple. It comes in a format of an injection into the arthritic joint.
If the patient is the source of the stem cell (Autologous stem cell) his/her physician has to harvest the stem cells from adipose tissue (150cc fat, mini-liposuction procedure) or bone marrow (bone marrow aspiration).
With minimal cell processing, the harvested stem cell is ready for use on the same day. Following harvesting, the stem cell is injected into the targeted joint with image guidance.
The patient will be observed for an hour or so prior to discharge.
There may be some discomfort from site of stem cell harvest, which is often self-limiting and well managed with over-the-counter medication.
The result of the stem cell treatment is often not apparent for the first 4-6 weeks after the treatment. The symptoms gradually improve over time.
The optimal time to see the results is within 3-6 months after the treatment. Your physician may obtain comparative x-rays 6-12 months after the treatment. You may resume normal exercises 3 weeks after treatment.
If the stem cells are a transplantation from a healthy donor to your body (Allogenic stem cell) for example, from umbilical cord blood or placental/amniotic fluid, these are received the night before your treatment from the vendor in a fresh frozen format.
On the day of your procedure, the stem cells are diluted with saline and injected into the targeted joint with image guidance.
As there is no harvesting involved, this treatment is very quick and requires very little recovery. Patient is often in the office less than 30 minutes.
The optimal time to see the results would be within 3-6 months after the treatment. You may resume normal exercises 3 weeks after treatment.
As with any treatment, there are certain risks to stem cell therapy. These are the potential risks that may occur with such treatment. The risk of treatment is divided based on multiple factors.
Immune reaction: In case allogenic stem cell, graft-versus-host immune reaction (GVHD), undesired immune response and tissue rejection is a possible. GVHD may happen at any time after your transplant. Autologous stem cells do not carry such a risk (MSC have low immunogenicity and are immunomodulatory). Symptoms of immune reaction may include muscle, joint pain, shortness of breath, vision changes, skin changes, rashes, yellow tint in the skin, dry mouth, mouth sores, abdominal pain and GI symptoms including diarrhea and nausea of vomiting.
Cell characteristic: With any lives cells, there is a possibility of tumorigenic potential or unwanted biological effect in likes of differentiating into an unwanted cell type. In case of excessive proliferation, benign or malignant neoplasm is possible.
Risk of local or systemic infection: There is risk of infection associated with the actual injection procedure. Infection can undersurface, into the joint or become systemic. Often the source of infection is bacteria on the skin which could be minimized by means of sterile technique.
Disease transmission or sample contamination: When stem cells are acquired from a donor, there is also the potential disease transmission from the donor to recipient. There is a standard CMS mandated list of blood testing which is performed on any donors tissue.
This test is not performed by the treating physician, but it is conducted by vendor supplying the stem cell. Understanding that despite standardized testing, there is always a potential risk for cell line contamination, and disease transmission is critical for the patient prior to accepting this treatment.
Stem cell contamination: Contamination by adventitious agents (viral/bacterial/mycoplasma/fungi, prions, parasites) whether the cells are allogenic or autologous during or after harvesting is possible.
Engraftment at an unwanted location
Donor site infection: In case of autologous stem cell, there are potential complications associated with harvesting the stem cell including localized pain, localized systemic infection, development of fat emboli, as well as vascular and cerebrovascular complications.
Organ damage at time of harvest
Low risk of teratoma
Lack of efficacy and continued symptoms for which stem cell treatment was recommended
Patients will experience some soreness or bruising from the abdominal area where the adipose or fat tissue has been harvested by the surgeon. This can last between 2-4 weeks after the treatment.
How much does the treatment cost?
In the United States mesenchymal stem cell therapy is considered investigational for all orthopedic applications. Until numerous double-blind randomized studies are performed, and hopes are that at some point in near future, it will not be covered by the insurance. For this reason, this service is an out-of-pocket expense to the patient. In this practice, the cost of a single joint stem cell treatment is 3,800USD. There is a 50% discount for second joint treated when autologous stem cell is used.
These are some resources who provide medical loans for procedures CreditKarma.com, Prosper.com. LightStream.com/med-loans. They are not affiliated with our practice.
NIH and FDA Stance on Stem Cell Therapy
According to the United States National Institute of Health (https://stemcells.nih.gov) “Pluripotent stem cells offer the possibility of a renewable source of replacement cells and tissues to treat a myriad of diseases, conditions, and disabilities including Parkinson's disease, ALS, spinal cord injury, burns, heart disease, diabetes, and arthritis.”
As of November 2017, FDA has a different stance on stem cell treatment. According to the FDA, “Stem cell products have the potential to treat many medical conditions and diseases. But for almost all of stem cell products, it is not yet known whether the product has any benefit—or if the product is safe to use.
The only stem cell-based products that are FDA-approved for use in the United States consist of blood-forming stem cells (hematopoietic progenitor cells) derived from cord blood. Bone marrow also is used for these treatments but is generally not regulated by the FDA”. ( www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm). Currently treatment of osteoarthritis with stem cell treatment is considered experimental in the United States. Stem cell therapy is in compliance with CFR21 Part 1271 (1271.15.b). Stem cell procedures are not new to the United States.
Bone marrow transplants (stem cell transplants) used to treat patients with leukemia is a similar treatment; bone marrow transplants also, are not approved by the FDA but listed as an exception as stated in CFR 1271.15.b.
Studies to review:
Cytotherapy. 2018 Feb 7. pii: S1465-3249(18)30001-X. doi: 10.1016/j.jcyt.2017.12.009. Intra-articular knee implantation of autologous bone marrow-derived mesenchymal stromal cells in rheumatoid arthritis patients with knee involvement: Results of a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial.
Regen Med. 2018 Feb 8. doi: 10.2217/rme-2017-0152. [Epub ahead of print] Human adipose-derived mesenchymal stem cells for osteoarthritis: a pilot study with long-term follow-up and repeated injections.
Arthrosc Tech. 2017 Oct; 6(5): e1761–e1766. Published online 2017 Oct 2. doi:10.1016/j.eats. 2017.06.048 PMCID: PMC5795060. Adipose-Derived Stem Cell Transplant Technique for Degenerative Joint Disease.
Curr Opin Rheumatol. Author manuscript; available in PMC 2014 Jan 1.Published in final edited form as:Curr Opin Rheumatol. 2013 Jan; 25(1): 119–126. doi: 10.1097/BOR.0b013e32835aa28dPMCID: PMC3616879NIHMSID: NIHMS453933. Stem cell-based therapies for osteoarthritis: Challenges and opportunities.
Trophic Activity and Phenotype of Adipose Tissue-Derived Mesenchymal Stem Cells as a Background of Their Regenerative Potential