Chronic Knee Pain and Osteoarthritis. How Can Stem Cells Help in The Disease Management and Improve Your Lifestyle?

Regenerative medicine offers hope for treating degenerative and genetic diseases. One of its main goals is to repair damaged tissues by developing ways to transplant pluripotent or multipotent stem cells, which have the ability to transform into many different types of cells. We can improve knee, shoulder and hips chronic pain with the use of mesenchymal stem cells. The most important cause of knee pain is osteoarthritis and well discuss its pathogenesis and how we can intervene and stop its degenerative process.

Since 2020, Osteoarthritis has been the fourth leading cause of disability worldwide. It commonly affects the knees, hips, hands, feet, and spine, with the knees being the most affected, responsible for nearly 85% of osteoarthritis cases globally, followed by the hands and hips. (Chongtao Zhu, Wei Wu, Xiaowen Qu, 2021).

What is osteoarthritis?

We can define osteoarthritis as a chronic and degenerative disease where the cartilage in the joints wears down over time and causes pain. It can be caused by mechanical stress, injuries to ligaments, or genetic issues affecting the cartilage and bones. As the protective cartilage layer breaks down, it leads to pain, swelling, and difficulty moving the joint. During this process, proteins from the cartilage, like type II collagen and enzymes called metalloproteinases, are released into the bloodstream. (Joan C. Marini, Antonella Forlino, 2012).

People with osteoarthritis experience chronic pain, stiffness, limited movement, and joint tenderness, with the most noticeable issue being the breakdown of cartilage due to tissue degeneration. This condition leads to physical weakness, mental stress, pain and a reduced quality of life.To manage osteoarthritis, both non-medication and medication-based treatments are used. Non-medication options like self-care, regular exercise, and weight control are recommended as the first steps in treatment. Medications, such as paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs), are suggested when non-medication methods don’t provide enough pain relief. (Chongtao Zhu, Wei Wu, Xiaowen Qu, 2021).

What factors increase the risk of developing osteoarthritis?

The development of knee pain and osteoarthritis is mainly linked to being overweight, obesity, being female, and having had a previous knee injury. Diabetes is also seen as a risk factor that can worsen knee osteoarthritis. According to Giuseppe Musumeci et al. (2015) non modifiable risk factors include the following ones:

1.      Recent studies have identified over 80 gene mutations linked to the development of osteoarthritis.

2.      Epigenetic changes, which refer to heritable alterations that don’t affect the DNA sequence itself, also play a role in osteoarthritis. These changes happen more quickly and are influenced by the cell's environment.

3.      Aging. Research on aging shows that stress or damage to cells can lead to long-term inflammation, which in turn contributes to diseases related to aging. This cellular response creates a condition similar to what is seen in osteoarthritis cartilage cells, where certain substances like cytokines, chemokines, and proteases (which are proteins and enzimes that specialize in pain signaling and degenerative processes) are produced.(Richard F Loeser, 2011)

4.      Gender. Studies on osteoarthritis show that there are important differences in how the disease develops in men and women. Women tend to have higher rates of osteoarthritis in their hands, feet, and knees compared to men. This suggests that hormones might play a role in how the disease progresses. Additionally, differences in bone and ligament structure, such as strength, alignment, flexibility, and cartilage volume, may also contribute to the variations seen between men and women.

5.      Ethnicity. Several studies in the United States have shown that there are differences in how often knee osteoarthritis occurs between African Americans and white individuals. For instance, data from the Third National Health and Nutrition Examination Survey revealed that African Americans were 50-65% more likely to experience radiographic knee osteoarthritis and painful knee osteoarthritis compared to whites. (Leigh F. Callahanet et al., 2021).

What can I change in my lifestyle to achieve a better life quality and reduce pain?

As we discussed earlier, there are non modifiable factors that play an important role in the pathogenesis of osteoarthritis, nonetheless there are also modifiable factors, and we can greatly intervene and decrease the degenerative process if we change our habits.

Having a body mass index (BMI) in the healthy range is associated with lower pain levels, as well as being physically active for at least 150 min/week. Exercise plus a diet high in fruits and vegetables is important in weight maintenance, and increasing fruit consumption is important for overall health. Engaging in a reasonable amount of low-impact exercise can help strengthen the muscles around the joints, prevent obesity, boost mood and mental health, and maintain function while delaying disability. Research shows that exercise programs consistently reduce pain and enhance function in adults with osteoarthritis. (Erin Conelly et al., 2015).

The important role that stem cells play in the management of osteoarthritis.

Mesenchymal stem cells offer several key advantages over other managements for treating degenerative joint diseases. Their paracrine activity, which involves the release of signaling molecules to adjuvant cells in the joint, is particularly helpful for managing osteoarthritis.

Mesenchymal stem cells have anti-inflammatory and immune-regulating properties that play a crucial role in repairing damaged joint tissues. These stem cells interact with immune cells, helping to regulate various immune functions, promote tissue repair, and prevent inflammation. One of the main benefits of using mesenchymal stem cells for osteoarthritis treatment is their ability to turn into chondrocytes, which are essential for cartilage health. They can also help protect chondrocytes from dying and slow down the overall degeneration process through their signaling effects. Additionally, mesenchymal stem cells modulate the immune system by suppressing certain self defense responses, releasing important signaling molecules, and inhibiting the activity of certain immune cells. The surrounding environment influences whether mesenchymal stem cells exhibit more pro-inflammatory or anti-inflammatory effects. (Michael Thoene, Ewa Bejer-Olenska and Joanna Wojtkiewicz, 2023).

Is there any scientific evidence?

A lot of research has been done on mesenchymal stem cells to help manage osteoarthritis because they work in different ways. Many small studies have shown that mesenchymal stem cells can help reduce pain and other symptoms of osteoarthritis, and in some cases, they even improved cartilage structure (Chahal J, Gómez-Aristizábal A, Shestopaloff K, et al., 2019).

A review of sixty-one studies with 2,390 patients (twenty-nine using mesenchymal stem cells from fat and thirty using those from bone marrow) found no clear answer on which type is better for treating osteoarthritis (Jevotovsky DS, Alfonso AR, Einhorn TA, et al., 2018). Mesenchymal stem cells from bone marrow seem to have a greater ability to form cartilage, while those from fat appear to help prevent cartilage cells from getting bigger and may slow down the progression of osteoarthritis (Jo CH, Lee YG, Shin WH, 2014).

One study compared how well different types of mesenchymal stem cells worked and found that all of them could be helpful for managing osteoarthritis. Additionally, a meta-analysis of eleven clinical trials with 582 patients suffering from knee osteoarthritis evaluated the safety and effectiveness of mesenchymal stem cell therapy and found no serious side effects related to the implantation of mesenchymal stem cells (Cameron Joseph Shegos, Arooj Fatima Chaudhr, 2021).

Conclusion

Mesenchymal stem cells present a promising avenue for the management of osteoarthritis, offering potential benefits in reducing pain, improving joint function, and even repairing damaged cartilage. By harnessing their anti-inflammatory and regenerative properties, we may slow down the progression of this degenerative disease and improve quality of life for patients. Combined with lifestyle changes such as regular exercise, a healthy diet, and weight management, stem cell therapy offers a comprehensive approach to tackling osteoarthritis and managing chronic knee pain effectively. Although more research is needed, the evidence so far suggests that stem cells could play a vital role in the future of osteoarthritis treatment.

References 

1.     Cameron Joseph Shegos, Arooj Fatima Chaudhr, (2021)

2.     Chahal J, Gómez-Aristizábal A, Shestopaloff K, et al. (2019) Bone Marrow Mesenchymal Stromal Cell Treatment in Patient with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation. Stem Cells Transl Med 2019;8:746-57

3.     Chongtao Zhu, Wei Wu, Xiaowen Qu. (2021). Mesenchymal stem cells in osteoarthritis therapy: a review. Am J Transl Res 13(2):448-461

4.      Erin Conelly et al., (2015) Modifiable lifestyle factors are associated with lower pain levels in adults with knee osteoarthritis. Pain Res Manag Vol 20 No 5 September/October 2015

5.     Giuseppe Musumeci et al. (2015) Osteoarthritis in the XXIst Century: Risk Factors and Behaviours that Influence Disease Onset and Progression. Int. J. Mol. Sci. 2015, 16, 6093-6112

6.     Jevotovsky DS, Alfonso AR, Einhorn TA, et al. (2018) Osteoarthritis and stem cell therapy in humans: a systematic review. Osteoarthritis Cartilage 2018;26:711-29

7.     Joan C. Marini, Antonella Forlino, (2012) Replenishing Cartilage from Endogenous Stem Cells. n engl j med 366;26

8.     Jo CH, Lee YG, Shin WH, et al. (2014) Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells 2014;32:1254-66

9.     Leigh F. Callahanet et al., (2021) Racial/ethnic, socioeconomic and geographic disparities in the epidemiology of knee and hip osteoarthritis. Rheum Dis Clin North Am. 2021 February ; 47(1): 1–20

10.  Michael Thoene, Ewa Bejer-Olenska and Joanna Wojtkiewicz, (2023) The Current State of Osteoarthritis Treatment Options Using Stem Cells for Regenerative Therapy: A Review. Int. J. Mol. Sci. 2023, 24, 8925.

11.  Richard F Loeser, (2011) Aging and Osteoarthritis. Curr Opin Rheumatol. 2011 September ; 23(5): 492–496.