By Sairam Atluri MD
Does Stem Cell Therapy Work in Knee Pain from Arthritis? Explanation of Clinical Trials for Patients.
July 21, 2018

https://www.stemcures.com/does-stem-...-for-patients/

If you are suffering from knee pain due to arthritis and are exploring Stem Cell options, you probably had these questions.

Are there any clinical trials for stem cells to treat knee arthritis?
Does stem cell therapy work in knee pain?
Can stem cells be an alternative to total knee replacement?
Do stem cells regenerate knee cartilage?
I looked into the medical literature to find answers. I was looking specifically for FDA allowed treatments.

Why did I look for only FDA allowed treatments? Because legitimate stem cell clinics offer FDA compliant treatments.

So that restricted me to only bone marrow stem cells. I eliminated cultured or expanded bone marrow stem cells. What are Cultured stem cells? These are stem cells are taken out of your bone and cultured in a lab to increase the numbers. They are then re-injected into the areas of pain. They are not approved by FDA. Since FDA does not also allow Allogenic bone marrow stem cells [stem cells from others], I did not include their studies. I also ignored Fat, Amniotic, Umbilical Cord stem cells as they are also not allowed per FDA regulations. I also did not include any study which involved surgical placement of stem cells.

To summarize, only studies which met the following criteria were analysed in this blog.

Patient’s own bone marrow stem cells
After centrifugation and concentration, Stem cells were immediately injected back into the knee
Stem cells were placed into the knee percutaneously [using needles and not surgery]
Pain coming from osteoarthritis of the knee
There were a lot of clinical trials for stem cells to treat knee arthritis. However, only 7 studies specifically used bone marrow stem cells to treat knee pain. I will be talking about these studies in this blog.

This study published by Dr.Hernigou in January of 2018 says that stem cell therapy is better than knee replacements.
Here, 30 patients with bilateral knee osteonecrosis were randomly assigned to receive either the traditional total knee replacement in one knee or their own bone marrow stem cells in the other knee. Stem cells were injected into the 2 knee bones. These patients were followed for an average of 12 years. In terms of pain relief, both groups had similar decrease in pain scores. However, in the stem cell group, there was about 4% increase in the knee cartilage and a 3cm cubic area decrease in the bone arthritis. Most importantly, 21 of the 30 patients were satisfied with stem cell therapy compared to only 9 of the 30 patients who had the knee surgery. 6 of the 30 knees which were operated required a second surgery where as only 3 in the stem cell group needed a second surgery. 30% of patients in the surgery group had blood transfusion versus none in the stem cell group. 15% of patients in the surgery group had clots develop in their legs. None of the patients in the stem cell group had clots. This is important to note because these clots in the leg, if undetected can travel to the lungs and cause death.No major side effects were reported in the stem cell group.

To summarize this clinical trial, stem cells provided similar relief to total knee replacement but had more patient satisfaction, less complications and less revision surgery. Regeneration of knee cartilage and decrease in the bone arthritis was also seen in the stem cell patients.

This study is important because it is the only study to date which compared the efficacy of bone marrow stem cells with total knee replacement. It is also the only study which tracked outcomes for about 12 years.

Does stem cell therapy work in knee pain from Arthritis? According to this elegant study by Hernigou, IT DOES WORK.

Can stem cells be an alternative to total knee replacement? According to this study, IT SEEMS LIKE A BETTER ALTERNATIVE.

Do stem cells regenerate knee cartilage? Based on MRI findings in this study, YES.

A large study by Dr.Centeno published in September of 2015 says that stem cell therapy works and the dose of the Stem Cells matters.
In this study, 373 patients that received stem cell injections intraarticularly, either with ultrasound or flouroscopy, to treat 424 osteoarthritic knee joints. Most joints were diagnosed with early stage knee osteoarthritis. TNC [Total Nucleated Cell] count is a surrogate marker for the number of stem cells. He divided patients into two groups. One group had a lower (≤4 × 108) cell count and the second group had a higher (>4 × 108) cell count. There were 185 patients in the high cell count group and 224 in the lower group. The stem cells were mixed with platelet lysate and injected into the joint. If some patients exhibited meniscal injury, the meniscus was also injected. Patients in both the higher and lower cell counts groups showed improvement in pain and function. However patients in higher cell count group received 50% more relief than the lower group. This underscores the importance of proper aspiration technique to maximize the stem cell count. No major side effects were reported.

This study is important because of large number of patients and they followed for more than a year.

Does stem cell therapy work in knee pain from Arthritis? According to this large study by Centeno, IT DOES WORK AND IS DOSE DEPENDENT.,

Can stem cells be an alternative to total knee replacement? According to this study, IT SEEMS LIKE A POSSIBLE ALTERNATIVE.

Do stem cells regenerate knee cartilage? This was not addressed in the study.

Another big study, also from Dr.Centeno, published in September 2014 shows that bone marrow stem cells work. Addition of fat graft did not improve results.
In this study 840 procedures were performed in 742 patients with knee arthritis. Bone marrow concentrate injected intra-articularly, either with ultrasound or flouroscopy in the knee. 224 were done with adipose graft and 616 were done without. The stem cells were mixed with platelet lysate and injected into the joint. If some patients had meniscal injury, the meniscus was also injected. Although functional improvement was mixed, pain relief was observed in both groups even after one year. Addition of adipose graft did not improve results. No major side effects were reported.

This study is important as it had the largest number of patients so far and they followed for more than a year.

Does stem cell therapy work in knee pain from Arthritis? According to this large study by Centeno, IT DOES WORK AND ADDITION OF FAT GRAFT DID NOT IMPROVE RESULTS.

Can stem cells be an alternative to total knee replacement? According to this study, IT SEEMS LIKE A POSSIBLE ALTERNATIVE.

Do stem cells regenerate knee cartilage? This was not addressed in the study.

Study from Dr.Oliver published in 2015 showed that bone marrow stem cells along with fat graft works.
In this study, 70 patients with moderate to severe knee osteoarthritis received intraarticular bone marrow stem cells along with fat graft. Ultrasound guidance was used inject the joint capsule. Even after 180 days, patients reported pain relief and increase in activity. No major side effects were reported.

Does stem cell therapy work in knee pain from Arthritis? According to this study, IT DOES WORK ALONG WITH THE ADDITION OF FAT GRAFT.

Can stem cells be an alternative to total knee replacement? According to this study, IT SEEMS LIKE A POSSIBLE ALTERNATIVE.

Do stem cells regenerate knee cartilage? This was not addressed in the study.

The study reported by Dr.Shaw in June of 2018 reveals that small doses of stem cells injected at 4 different times helps with knee arthritis.
In this study, 15 patients [20 knees] with moderate to severe knee osteoarthritis had bone marrow stem cells injected 4 times over a period of about 9 weeks. Procedure was performed under ultrasound guidance into the knee joint capsule. Traditionally 60 cc of bone marrow is aspirated and centrifuged to generate 3-5 cc of bone marrow concentrate which is full of stem cells. Here only 20 cc of bone marrow was aspirated. So, small doses were injected 4 times instead of one large dose one time. With respect to subjective overall improvement, the largest improvement (43.8%) occurred after the first treatment. The next 3 treatments were associated with a 7.95% mean improvement resulting in a mean 67% total overall improvement after 4 treatments. In addition, 7 knees reported 80% or more overall improvement. Functionality also improved with each treatment. No major side effects were reported.

Does stem cell therapy work in knee pain from Arthritis? MULTIPLE SMALL DOSE BONE MARROW INJECTIONS DO WORK .

Can stem cells be an alternative to total knee replacement? According to this study, IT SEEMS LIKE A POSSIBLE ALTERNATIVE.

Do stem cells regenerate knee cartilage? This was not addressed in the study.

The study from Dr.Shapiro which was published in 2016 shows that “salt water” is as good as stem cells. Both gave good pain relief.
In this study, 25 patients with bilateral knee pain from osteoarthritis [mild to moderate] received bone marrow stem cells into one knee and saline [salt water] in the other knee. Both the procedures were done under ultrasound. Interestingly both groups reported significant pain relief along with increase in function up to at least 6 months. Interestingly, even the authors struggled to explain why saline provided similar relief as stem cells. No major side effects were reported.

Does stem cell therapy work in knee pain from Arthritis? BONE MARROW STEM INJECTIONS DO WORK AND INTERESTINGLY GIVE SIMILAR RELIEF AS SALINE. EVEN THE AUTHORS WERE UNABLE TO EXPLAIN WHY SALINE PROVIDED PAIN RELIEF.

Can stem cells be an alternative to total knee replacement? According to this study, IT SEEMS LIKE A POSSIBLE ALTERNATIVE.

Do stem cells regenerate knee cartilage? This was not addressed in the study.

A small study by Dr.Rodriguez showed that stem cells help with patients with low grade arthritis.
In this study, 10 patients with early osteoarthritic knees joints were injected with stem cells. Even after more than a year, most patients reported pain relief along with improvement in function. No complications were noted.

Does stem cell therapy work in knee pain from Arthritis? BONE MARROW STEM INJECTIONS DO WORK.

Can stem cells be an alternative to total knee replacement? According to this study, IT SEEMS LIKE A POSSIBLE ALTERNATIVE.

Do stem cells regenerate knee cartilage? This was not addressed in the study.

Summarized the findings from the above studies are found in the Table below



Author Patients Arthritis Area Injected Pain Relief Follow up in Years Functional Improvement Regeneration seen Complications
Henrigou 30 Severe SC Yes 12 Yes Yes None
Centeno 373 Early stage IA Yes >1 Yes NE None
Centeno 742 Mild to Severe IA Yes >1 Yes NE None
Oliver 70 Moderate to Severe IA Yes 0.5 Yes NE None
Shaw 15 Moderate to Severe IA Yes 0.25 Yes NE None
Shapiro 25 Mild to Moderate IA Yes 0.5 Yes NE None
Rodriquez 10 Early IA Yes >1 Yes NE None


NE: Not Evaluated, SC: Subchondral, IA: Intra-articular


CONCLUSION

7 studies with a total of 1265 patients, evaluated the efficacy of stem cells for arthritis pain in the knee. All the studies reported pain relief with improvement in function. Most importantly there were no side effects or complications. Based on the current available clinical studies, bone marrow stem cells seem like a viable option to treat knee arthritis and maybe a good option to avoid surgery.

In our clinic, we are seeing good results as reflected in the above studies. Watch the video to see Carole’s pain relief from knee arthritis using her own bone marrow stem cells. https://youtu.be/DxESq8KKaP8