Mesenchymal Stem Cell Therapy Combined with Arthroplasty for Knee Osteoarthritis Treatment

What is Osteoarthritis? 

Osteoarthritis (OA) is a chronic and progressive condition, which can result in significant pain and loss of function. Symptomatic OA, while often regarded as an age-related condition, is not only a disease of the elderly as it has a prevalence rate of 10% of males and 18% of females over the age of 45 years. Alarmingly, there has been an observed increase in the number of patients undergoing total joint replacement under the age of 65.

What are Current Treatment Options? 

Conservative pharmaceutical management of knee OA is aimed at symptomatic control and does not halt progressive joint degeneration. These therapies demonstrate often only modest benefits and may have unwanted side effects.

Other treatment options include:

• Weight loss. Losing even a small amount of weight can significantly decrease knee pain OA. 
• Pain relievers and anti-inflammatory drugs. They can have side effects when taken chronically.
• Exercise. Strengthening the muscles around the knee makes the joint more stable and decreases pain. 
• Injections with corticosteroids or hyaluronic acid to the knee. They can achieve pain relief but normally the effect decreases with time. 
• Physical therapy.  It can strengthen the muscles around the knee and increase knee flexibility.
• Surgery. It can vary from arthroscopy which is less invasive to a complete joint replacement. 

What Causes OA? 

It was previously considered a “wear and tear” causality, we now understand that OA is the result of an imbalance between anabolic/reparative and catabolic/proinflammatory pathways with the instigation of this imbalance associated commonly with abnormal mechanical forces operating at the joint. 

Structurally OA is recognized as a loss of load-bearing cartilage and may include osteophyte formation, subchondral sclerosis and cyst formation, and periarticular synovitis.

Chondrocyte cell senescence as a result of mechanical or biological stressors has been shown to be accompanied by an observed increase in a cascade of inflammatory cytokine expression leading to a procatabolic state with resultant matrix degradation and development of OA.

Alternative Treatment Options 

Mesenchymal stem cells (MSCs) have the ability to differentiate along a mesodermal lineage including bone and cartilage and have been of considerable research interest in their potential to assist in musculoskeletal repair and regeneration. 

However, their observed anti-inflammatory role and expression of anabolic trophic cytokines through both paracrine cell to cell interaction are now considered to be the mechanism of action and responsibility for their observed potential. 

Clinical trials have indicated the benefits of its use for OA, seeing functional and pain improvements and evidence of disease modification with radiological confirmed OA stabilization, improvement in cartilage quality, and regrowth. 

Combination with Surgical Procedures 

Surgical techniques used to promote structural regeneration at the site of Grade IV (full thickness) chondropathologies with resultant pain and functional improvements include arthroscopic microfracture and arthroscopic abrasion arthroplasty (AAA). 

Past research has shown histopathology of fibrocartilage formation after bone marrow stimulation techniques including AAA or microfracture. Arthroscopic abrasion arthroplasty is used to restore knee articular lining by rasping damaged areas to promote bleeding, and formation of fibrocartilage, or scar tissue, which covers the damaged area.

Research Study Results

A study published in October 2020 in the journal Regenerative Medicine by Julien Freitag and colleagues evaluated the safety and efficacy of adipose-derived mesenchymal stem cell (ADMSC) therapy in combination with arthroscopic abrasion arthroplasty in advanced knee OA. 

They included 27 patients with Grade IV OA of the knee and underwent arthroscopic abrasion arthroplasty (AAA) and ADMSC therapy with 50 million ADMSCs at baseline and at 6 months, with clinical outcomes assessed over 36 months. 

All intra-articular injections were performed under ultrasound guidance with the area of injection prepared using standard sterility protocols. Prior to injection of ADMSCs, 2 ml of 1% lidocaine was infiltrated superficially to the joint capsule.

Under direct ultrasound visualization and using a superolateral approach, the resuspended autologous ADMSCs in 3 ml of carrier media were injected intra-articularly into the knee joint cavity.

The treatment was well tolerated with no serious adverse events. Clinical significant improvements in pain and function were observed and hyaline-like cartilage regeneration was seen in all patients. MRI was performed at 12 and 36+ months and showed successful and sustained cartilage regeneration. 

Consistent and progressive improvement in pain and function was seen across the period of follow-up. A mean reduction in the pain level of 73.2% was observed. Of the 26 participants who completed 36 months of follow-up, satisfaction with treatment, as represented by PGIC, indicated overall satisfaction with 92.5% of participants indicating that they were ‘very much improved’ or ‘much improved’ at the completion of follow-up at 36 months.

The researchers concluded that the therapy is safe and effective in reducing pain, increasing functional capacity, and can have structural improvements, making the therapy a preservation technique that could prevent knee replacement in patients with advanced knee OA.

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Source: 

Julien Freitag, et al. Mesenchymal stem cell therapy combined with arthroscopic abrasion arthroplasty regenerates cartilage in patients with severe knee osteoarthritis: a case series. Regenerative Medicine, Vol. 15, No. 8. Oct 2020.  https://doi.org/10.2217/rme-2020-0128 

https://www.webmd.com/osteoarthritis/ostearthritis-of-the-knee-degenerative-arthritis-of-the-knee

Image from: 

https://www.topdoctors.co.uk/medical-dictionary/cartilage-repair