What is Osteoarthritis?
Osteoarthritis is the most common type of osteoarthritis characterized by degeneration of the articular cartilage and ultimately joint destruction. It is estimated that 27 million Americans 25 years of age and older have clinical osteoarthritis of some joint, with a higher percentage of affliction in the older population.
Human aging is associated with bone and joint degenerative changes that include loss of bone density and ligament flexibility. Chronic musculoskeletal pain accounts for the most medical complaints in the United States with nearly 15 million Americans reporting dysfunction in activities of daily living (ADL’s) as a result of a musculoskeletal ailment.
In 2005, one in two adults greater than 18 years of age reported experiencing musculoskeletal pain lasting 3 months or longer.
Osteoarthritis is a progressively debilitating and irreversible disease that affects mostly cartilage and associated changes in the bone and synovium. Once considered only in the elderly, osteoarthritis is seen in younger patients, affecting all joints such as the hands, knees, hips and the spine being the major problematic sites.
Generally, cartilage defects in Osteoarthritis are usually large, unconfined and affect more than one location
Acute cartilage injury often occurs in normal young patients and probably requires localized treatment in contrast to patients with Osteoarthritis in the elderly where the entire joint surface will require treatment. This cartilage damage eventually leads to decreased function and loss of mobility and autonomy for the patient
Osteoarthritis has striking impact on quality of life and economic costs.
Osteoarthritis is a complex condition with broad pathology with clear links to other conditions such as neuropathic pain, depression, and sleep disorder, and is often characterized as a biomechanical disease associated with abnormal joint loading from obesity, joint instability, or trauma, and inflammation of the joints, and genetics.
There is a poor understanding in the disease mechanism of Osteoarthritis associated with:
- A lack of biomarkers of early disease.
- Slow progression.
- Signaling pathways, biomechanical events and cellular functions remain obscure.
Manifestations of Osteoarthritis include:
- Joint pain.
- Impairment to movement.
- Local tissue inflammation surrounding the joint.
Much of the Osteoarthritis research today has focused on the loss of articular cartilage by:
- Insufficient repair response
- Mechanical stresses.
- Aging or dead cells that cannot produce cartilage.
The synovium plays a crucial role in the development of Osteoarthritis of the joint. Synovial inflammation occurs in the majority of patients and is a predictive factor in the disease progression.
Infiltration of T cells and macrophages are increased in the synovium in early Osteoarthritis. This indicates synovial inflammation is a feature in early disease and might be an indicator of future tissue destruction.
The synovium seems to have two faces to its role in Osteoarthritis
- It may be the focus of effective repair responses involving local populations of mesenchymal stem cells (called MSC’s), where the MSC’s become activated and are capable of differentiating into cartilage, bone and other tissue which might provide repair cells to help to maintain healthy joints.
Current Treatment in Osteoarthritis
The current treatment strategies for Osteoarthritis are inadequate.
It is a striking fact that no appropriate pharmacological intervention, biological therapy or procedure prevents the progressive destruction of the osteoarthritic joint. All current treatment regimens produce symptomatic rather than regenerative results, for example:
- Non-steroidals for pain.
- Viscosupplementation with injection of sodium hyaluron (Synvisc)
- Nutraceuticals like chondroitin sulfate, omega 3- fatty acids, etc
Non-pharmacological and pharmacologic treatments are used for early and moderately early cases of Osteoarthritis, but protection of the articular cartilage has not been shown.
None of these treatments have a useful impact on the progressive loss of joint tissues that leads to the total joint replacement.
Total joint replacement can be successful resulting in enhanced mobility and reduction in pain, but surgical procedures come with associated risks, which include:
- Thrombosis, infection and a very high cost in hospitalization and rehabilitation.
- There is also an increased risks of Osteoarthritis after meniscus or ACL injury.
Mesenchymal STEM CELLS in Treatment of Osteoarthritis.
Osteoarthritis is associated with progressive and often severe inflammation. Because MSC’s have been shown to possess anti-inflammatory function, they are a suitable cell type for this purpose.
Several characteristics of MSC’s make them attractive in this respect.
- MSC’s migrate to, and engraft onto multiple musculoskeletal tissues, especially sites of injury.
- MSC’s at site of injury undergo site specific differentiation.
- MSC’s at the site can exert significant effects on the local environment and on resident endogenous tissue progenitor cells through direct or indirect interactions and soluble factors.
- MSC’s have shown potent anti-inflammatory and immunosuppressive activities.
All the above make MSC’s a promising candidate for cell therapy for diseases that often involve the immune system (OA and RA).
Degenerative changes seen in arthritic disease are associated with deletion of the MSC’s reservoirs or alternations in their activity, which might contribute to the development of Osteoarthritis.
MSC’s isolated from patients with endstage Osteoarthritis were found to be functionally deficient in their proliferative and differentiation abilities, whereby they had reduced ability to produce cartilage, fat and bone.
MSC’s (Mesenchymal STEM CELL injection) can have therapeutic effects in osteoarthritis, possibly through their trophic effect and anti-inflammatory and immunosuppressive activities, which can significantly affect their local environment in carrying out the regenerative function.
The Three Generations of Biologic Injectates
- Hyaluronic Acid (First Generation)
- Successful in the treatment of painful Osteoarthritis of the knee.
- Benefits covered by insurance.
- Limits include:
- Temporary effect.
- Best used in early osteoarthritis.
- PRP (Second Generation)
- Has demonstrated superior results compared to Hyaluronic Acid
- Adult MSC’s (Mesenchymal Stem Cells)
- More powerful than PRP.
- Function like mini drug stores to repair injury sites.
- Come from multiple sources like bone marrow and adipose.
- The adult STEM CELL is an undifferentiated cell that is held in reserve until replacement or repair is needed.
- It can turn into many cells.
MSCs can orchestrate a repair response in joints, muscles and tendons.