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The Research Behind Mesenchymal Stem Cells and Osteoarthritis

 
We briefly touched on the promising outcomes scientists have seen with Mesenchymal Stem Cell (MSC) therapy and osteoarthritis (OA) in our “Mesenchymal Stem Cells and Autoimmune Conditions” blog post.

Given that osteoarthritis is arguably one of the most promising areas for MSC therapy research, we thought that a dedicated blog for osteoarthritis was long overdue.

There’s been a lot of research into the use of MSC therapy to help alleviate pain and maintain function in cases of osteoarthritis — making it perhaps one of the most noteworthy areas for potential MSC applications.

First, let’s cover the basics:

What Is Arthritis?

Arthritis can be thought of as a catch-all term for joint inflammation and can be broadly categorized into two types: inflammatory arthritis and osteoarthritis.

Inflammatory arthritis refers to joint damage caused by various forms of autoimmune dysfunction, which we covered in a previous blog post, while the more common osteoarthritis refers to joint damage associated with wear and tear.

Osteoarthritis is a condition nearly synonymous with age, to the point that it’s less a question of “if” you’ll ever experience it but “when” — with over 22% of adults over 40 estimated to have osteoarthritis in just their knees alone.

Conventional treatment for osteoarthritis usually comes down to pain management, anti-inflammatories, and physical therapy, with more severe cases often leading to surgery in the form of joint replacements.

Considering the invasive nature of joint replacement procedures, as well as the advanced age of the people most often suffering from severe cases, it should be no surprise that researchers have been looking for a more effective, less-invasive way to alleviate the symptoms of osteoarthritis for quite some time.¹

Enter Mesenchymal Stem Cell Therapy.

What Are Mesenchymal Stem Cells?

Like most types of stem cells, Mesenchymal Stem Cells (MSCs) have demonstrated the ability to differentiate into other types of cells, giving them regenerative properties that may help promote tissue repair.

However, MSCs’ main claim to fame is the unique immunomodulating properties that make them “one of the most powerful anti-inflammatories there is,” as explained by Celltex Chief Medical Officer Dr. Stanley C. Jones in a recent webinar.

The process by which MSCs use their immunomodulating properties to modulate inflammation is complex, but it involves the MSCs’ ability to inhibit the appearance and activation of specific immune cells responsible for inflammation.

So, how does this relate to osteoarthritis?

While osteoarthritis isn’t caused by the immune system per-say, as a joint deteriorates from wear-and-tear the immune system induces an inflammatory response that contributes to further joint damage. By the time someone seeks medical help for osteoarthritis inflammation is often a serious problem.²

What’s more, the body can’t start the natural repair process for a joint that’s experiencing inflammation, making MSC therapy particularly suited for use in osteoarthritis since MSCs can reduce inflammation and induce regeneration simultaneously.²

With all of that in mind, it’s no surprise that osteoarthritis stands out as one of the most active, promising areas for research into MSC application.

What Does the Research Say About MSC Therapy and Osteoarthritis?

MSC therapy is likely safe and effective:

Clinicaltrials.gov lists fifty-three completed clinical trials investigating the use of MSC therapy for osteoarthritis, with many demonstrating positive results in symptom improvement, pain reduction, and even cartilage regeneration.²

• One meta-analysis on clinical trials for osteoarthritis of the knee showed “remarkable improvement of all clinical and functional scores.”³
• Another team stated that there was “strong evidence of autologous MSC being safe with generally positive clinical outcomes.”⁴
• A third group observed that “trials to date reveal robust clinical evidence hyaline cartilage can be regenerated suggesting it may become clinical practice in the near future.”⁵
• Centeno et al. reported on 102 people treated with MSCs for either osteoarthritis of the shoulder or rotator cuff injuries who demonstrated statistically significant improvements with no safety issues.⁶

*A note on individual joints: For the most part, clinical trials for osteoarthritis focus on a single joint, rather than on osteoarthritis as a whole.

Joints more commonly affected by osteoarthritis, like the knees, tend to get more attention — so a lot of the literature covered in this blog is referencing clinical trials into the effects of MSC therapy on osteoarthritis of the knees, specifically.

That being said, the similar pathology from joint to joint means that it’s not unreasonable to infer that results seen in one joint are likely to be seen in another. Of course, more research is needed to fully compare the effects of MSC therapy on different joints.⁷

MSC therapy may be more effective with higher quantities of stem cells:

One of the biggest questions surrounding MSC therapy is how many stem cells should be utilized and how often?

The number of stem cells used in a single therapy can vary wildly, but the research is starting to show that, when it comes to MSCs, more is better.

• Jo, et al. showed that individuals who received one hundred million cells per dose showed better outcomes than those who received either ten or fifty million cells per dose.⁸
• Lamo-Espinoa, Mora, et al. showed that individuals who received one hundred million cells per dose showed better improvements to their pain and function levels than those who received either hyaluronic acid or ten million stem cells per dose.⁹
• Zhao, et al. compared the results of groups who received ten, twenty, or fifty million cells per dose, with the fifty million cell group showing MRI improvements at the six-month mark.¹⁰
• Freitag, et al. observed better outcomes giving two doses of ten million cells over those receiving just a single dose.¹¹

One important takeaway from these dose comparisons is that, while higher cell dosage tends to show better results, groups receiving lower stem cell doses still showed more improvement than groups receiving conventional or placebo therapy.¹

Of the studies we reviewed for this blog, the lowest stem cell dose utilized was ten million cells. Some same-day stem cell therapies only offer stem cell doses in the hundreds of thousands, though, which could potentially impact the likelihood of positive results considerably.

Celltex’s Client Reported Outcomes:

Finally, let’s look at some of the results Celltex has seen from our clients with osteoarthritis.

The data below is based on two studies conducted by the Celltex Research & Development Team, one for osteoarthritis of the knees and another for osteoarthritis of the shoulders.
 

Osteoarthritis of the knee:

• 81% of Celltex clients with osteoarthritis of the knee reported improvement in one or more symptoms.
• 63% of Celltex clients with osteoarthritis of the knee demonstrated clinically important improvements in their level of pain.
• 68% of Celltex clients with osteoarthritis of the knee demonstrated clinically important improvements in their quality of life.

Osteoarthritis of the shoulder:

• 81% of Celltex clients with osteoarthritis of the shoulder reported improvement in one or more symptoms.
• 55% of physicians of Celltex clients with osteoarthritis of the shoulder noted improvement compared to previous radiology.
• Based on physician evaluation, the average Celltex client with osteoarthritis of the shoulder saw range of motion in the affected shoulder improve by over ten points.

 
For a more detailed look at these numbers, you can request a copy of our complete research overview.

The Takeaway: More Research is Needed

It’s worth repeating that osteoarthritis stands out as one of the most active, promising areas for research into MSC application — but there’s still plenty of research to be done.

To date, clinicaltrials.gov lists fifty-three completed clinical trials and seventy-three active trials investigating the use of MSCs for osteoarthritis, meaning that for all the exciting research we’ve discussed today there’s far more on the horizon.

To learn more about Mesenchymal Stem Cell research, check out our articles on MSCs and autoimmune or neurological disorders.

To see if MSC therapy might be an option for you, check out our general overview of stem cell therapy.

Finally, until the end of July 2023, we’re providing special offers for those suffering from joint pain, which you can learn more about here.

References:

1. Young, J., Rhodes, M. Safety of Autologous Adipose-Derived Mesenchymal Stem Cells in OA of the Knee.
2. Wang, LT., Ting, CH., Yen, ML., Liu, KJ., Sytwu, HK., Wu, K. K., Yen, B. L (2016). Human mesenchymal stem cells (MSCs) for treatment towards immune- and inflammation-mediated diseases: review of current clinical trials. J Biomed Sci 23, 76. https://doi.org/10.1186/s12929-016-0289-5
3. Migliorini, F., Rath, B., Colarossi, G., Driessen, A., Tingart, M., Niewiera, M., & Eschweiler, J. (2020). Improved outcomes after mesenchymal stem cells injections for knee osteoarthritis: results at 12-months follow-up: a systematic review of the literature. Archives of orthopaedic and trauma surgery, 140(7), 853–868. https://doi.org/10.1007/s00402-019-03267-8
4. McIntyre, J. A., Jones, I. A., Han, B., & Vangsness, C. T., Jr (2018). Intra-articular Mesenchymal Stem Cell Therapy for the Human Joint: A Systematic Review. The American journal of sports medicine, 46(14), 3550–3563. https://doi.org/10.1177/0363546517735844
5. Reissis, D., Tang, Q. O., Cooper, N. C., Carasco, C. F., Gamie, Z., Mantalaris, A., & Tsiridis, E. (2016). Current clinical evidence for the use of mesenchymal stem cells in articular cartilage repair. Expert opinion on biological therapy, 16(4), 535–557. https://doi.org/10.1517/14712598.2016.1145651
6. Centeno, C. J., Al-Sayegh, H., Bashir, J., Goodyear, S., & Freeman, M. D. (2015). A prospective multi-site registry study of a specific protocol of autologous bone marrow concentrate for the treatment of shoulder rotator cuff tears and osteoarthritis. Journal of pain research, 8, 269–276. https://doi.org/10.2147/JPR.S80872
7. Young, J., Rhodes, M. Safety of Autologous Adipose-Derived Mesenchymal Stem Cells in Osteoarthritis of the Shoulder.
8. Jo, C. H., Lee, Y. G., Shin, W. H., Kim, H., Chai, J. W., Jeong, E. C., Kim, J. E., Shim, H., Shin, J. S., Shin, I. S., Ra, J. C., Oh, S., & Yoon, K. S. (2014). Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem cells (Dayton, Ohio), 32(5), 1254–1266. https://doi.org/10.1002/stem.1634
9. Lamo-Espinosa, J. M., Mora, G., Blanco, J. F., Granero-Moltó, F., Nuñez-Córdoba, J. M., Sánchez-Echenique, C., Bondía, J. M., Aquerreta, J. D., Andreu, E. J., Ornilla, E., Villarón, E. M., Valentí-Azcárate, A., Sánchez-Guijo, F., Del Cañizo, M. C., Valentí-Nin, J. R., & Prósper, F. (2016). Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). Journal of translational medicine, 14(1), 246. https://doi.org/10.1186/s12967-016-0998-2
10. Zhao, X., Ruan, J., Tang, H., Li, J., Shi, Y., Li, M., Li, S., Xu, C., Lu, Q., & Dai, C. (2019). Multi-compositional MRI evaluation of repair cartilage in knee osteoarthritis with treatment of allogeneic human adipose-derived mesenchymal progenitor cells. Stem cell research & therapy, 10(1), 308. https://doi.org/10.1186/s13287-019-1406-7
11. Freitag, J., Bates, D., Wickham, J., Shah, K., Huguenin, L., Tenen, A., Paterson, K., & Boyd, R. (2019). Adipose-derived mesenchymal stem cell therapy in the treatment of knee osteoarthritis: a randomized controlled trial. Regenerative medicine, 14(3), 213–230. https://doi.org/10.2217/rme-2018-0161

About Celltex

Celltex Therapeutics Corporation is an international leader in cryopreservation, or banking, and culturing of autologous, adipose-derived Mesenchymal Stem Cells (MSCs) for therapeutic use and has remained committed to improving and maintaining clients’ quality of life. Celltex has the unique ability to do what no one else can: isolate, expand and cryopreserve your own MSCs to create your master cell bank, all from one small sample of your adipose tissue. This bank of MSCs can then be used to produce hundreds of millions of clinical-grade, genetically stable MSCs that are available for therapeutic use. To learn more about Celltex, visit www.celltexbank.com

Post Tags: adult stem cell therapy, arthritis, medical research, Orthopedics, pain relief, stem cell therapy