In this article I will present research to support the use of stem cell treatments for knee osteoarthritis. I will discuss newly published research by the Darrow Stem Cell Institute on the use of bone marrow derived stem cells and discuss the use of amniotic and placenta tissue treatments, umbilical cord blood treatments and adipose or fat derived stem cells. We will explore the newest research and clinical applications. I also invite you to ask your questions using the form below about your knee pain.
Before we get to updates on umbilical cord blood stem cells, let’s review the research we conducted at the Darrow Stem Cell Institute in Los Angeles, California on patients with knee osteoarthritis.
Short-Term Outcomes in Treatment of Knee Osteoarthritis With 4 Bone Marrow Concentrate Injections
Brent Shaw, Marc Darrow, MD JD : Darrow Stem Cell Institute, Los Angeles, CA, USA
Armen Derian : Mayo Clinic, Phoenix, AZ, USA
Clinical Medicine Insights: Arthritis and Musculoskeletal Disorders June 18, 2018
Preliminary research suggests that bone marrow concentrate (BMC), which contains mesenchymal stem cells and platelets, is a promising treatment for knee osteoarthritis. The aim of this study was to build on this preliminary research by reporting the short-term progress of 15 patients (20 knees) with knee osteoarthritis through 4 BMC (bone marrow derived stem cell treatments.)
The timetable of the four treatments:
- First treatment
- Second treatment approximately 14 days after first treatment.
- Third treatment, approximately 21 days after second treatment, 35 days after first treatment
- Fourth treatment, approximately 34 days after the third treatment. Approximately 69 days on average after first treatment
- The last follow-up was conducted a mean 86 days after the first treatment.
What we measured: Overall improvement percentage was compared after each treatment for the following:
- pain at rest
- pain during activity
- functionality scale scores
What we found:
- Patients experienced statistically significant improvements in active pain and functionality score after the first treatment.
- Additionally, patients experienced a mean decrease in resting pain after the first treatment, yet outcomes were not statistically significant until after the second treatment.
- On average, patients experienced:
- an 84.31% decrease in resting pain,
- a 61.95% decrease in active pain,
- and a 55.68% increase in functionality score at the final follow-up.
- Patients also reported a mean 67% total overall improvement at study conclusion. Outcomes at the final follow-up after the fourth treatment were statistically significant compared to outcomes at baseline, after first treatment, after second treatment, and after third treatment.
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Supportive research on bone marrow derived stem cells
A study in the journal Cytotherapy. (1) , examined the injection of mesenchymal stromal cells (bone marrow derived stem cells) as a treatment for knee osteoarthritis.
The study subjects were randomized into two groups:
- A single injection of stem cells, or
- A placebo injection of saline solution
Patients were followed up for 6 months after the injection.
Scores were recorded for :
- Pain level and function improvements to include: walking distance, painless walking distance, standing time and knee flexion compared with the placebo group at 3 and 6 months
The conclusion of this research was the bone marrow derived stem cell injection demonstrated safety and effectiveness.
- Bone marrow derived stem cell injection provided significant and clinically relevant pain relief over 6 months versus placebo.
Researchers at Georgia Regents University are looking at stem cells for osteoarthritis treatment. The reason? “Current pharmacological treatment strategies are ineffective to prevent the osteoarthritic progression; however, cellular therapies have the potential to regenerate the lost cartilage, combat cartilage degeneration, provide pain relief, and improve patient mobility.” Among the cellular therapies are bone marrow-derived stem cells which have been shown to have a higher chondrogenic capability (the ability to make cartilage) than fat derived stem cells, and they have been studied more extensively than the fat derived stem cells.(2)
- Chinese university researchers writing in the journal Molecular medicine reports found that bone marrow stem cells increase the cell proliferation of chondrocytes (cartilage builders) and inhibit inflammatory activity in osteoarthritis. In common language, stem cell injections regrow cartilage and halt damaging chronic inflammation.(3)
- In one of the most cited research studies on the subject, with over 178 listed publications referencing their study, doctors in Iran found that six months after stem cell treatments, patients displayed an increase in cartilage thickness, extension of the repair tissue over the subchondral bone and a considerable decrease in the size of edematous subchondral patches (damage).(4)
As the above research shows, cartilage can be regrown, bone can be regrown, and chronic inflammation (swelling) shut off. The long-term outlook for the patients with bone marrow derived stem cells has to be thought of as a treatment with a curative effect.
Our conclusions about bone marrow derived stem cells for knee osteoarthritis
Returning to our own published research cited above, I would like to recap the learning points:
- We found that in the short-term, receiving multiple injections may be more effective than receiving a single BMC stem cell injection.
- Outcomes at the final follow-up after the fourth treatment were statistically significant compared with outcomes at baseline, after first treatment, after second treatment, and after third treatment.
- Functionality score increased after first treatment, illustrating that patients experienced an immediate benefit in performing everyday activities with less difficulty.
- By the second injection, patients began to report improvement with pain at rest. Patients then experienced additional decreases in resting pain with each treatment thereafter.
- The increase in mean functionality score with successive BMC treatments shows that increasing the number of BMC treatments improves patient performance in daily activities.
The present findings may provide new clinical insights into treating OA with BMC. If BMC treatments become more affordable or covered by insurance companies, there could be an increase in the number of patients receiving multiple BMC treatments for OA. If patients who reported improvement to a single injection received multiple, they may experience increased symptomatic relief such as the patients in our study. An additional finding illustrated that patients experienced a greater pain relief when injected with a high-nucleated cell count compared to a lower dose.21 Our study demonstrates that gradual increase in BMC injections in a short time period may be more effective than a single injection.
When patients were asked whether they experienced adverse side effects at each follow-up, the most common complaints were pain at the extraction site and inflammation at the injection site. Grinding, popping, and snapping sensations in the knee joint were common with specific movements, as was joint stiffness, especially 1 to 2 days following treatment. However, the stiffness generally resolved by the next follow-up visit.
LONG-TERM OBSERVATIONS ON RISK AND THE USE OF DONATED UMBILICAL CORD BLOOD STEM CELLS: THE FINDINGS OF A 7-YEAR STUDY.
In 2017, doctors reported their findings in the journal Stem cells translational medicine (5) of a seven-year observation of patients who had received human umbilical cords stem cell therapy for knee osteoarthritis:
Here are the safety learning points of this research:
- This study revealed that treatment with an allogeneic human umbilical cord blood stem cells is safe.
- The results of the study show that the patients had no significant adverse effects or undesired effects over the seven years of follow‐up.
- None of the study participants had substantial permanent degenerative disease.
- The study found no evidence of abnormal findings suggesting rejection or infection.
- The researchers suggest that the characteristics of the human umbilical cord blood stem cells such as hypoimmunogenicity (does not cause an immune system reaction) and immunomodulatory (the immune system does not consider these “foreign” cells to be invaders) activity contributed to the lack of the stem cells rejection.
- There were no cases of osteogenesis (bone mutation) or tumorigenesis over 7 years.
Here are the learning points regarding the outcome of the patient’s human umbilical cord blood stem cells knee osteoarthritis treatment:
Not only did the doctors report that none of the seven patients in the study needed to undergo knee replacement despite the severity of their degenerative knee disease, but umbilical cord blood stem cells appear to be safe and effective for the regeneration of durable articular cartilage in osteoarthritic knees.
RESEARCH ON UMBILICAL CORD BLOOD STEM CELL TREATMENT
In the Chinese journal of reparative and reconstructive surgery, (6) doctors reported on the effects of umbilical cord blood stem cell therapy on their patients. Here are the learning points of their study:
- Between January 2015 and January 2016, 36 patients with moderate or severe degenerative knee osteoarthritis were randomly divided into 2 groups of 18 patients each.
- Intra-articular injection of human umbilical cord stem cell suspension was performed once a month for 2 times as a course of treatment in the cell treatment group; sodium hyaluronate by intra-articular injection was used once a week for 5 times as a course of treatment in the control group.
- All patients of 2 groups received a course of treatment.
- The patients were followed up for 6 months.
- In the stem cell treatment group, standardized pain and function scores at 2-6 months after treatment were significantly better when compared with scores before treatment, and no recurrence of knee pain was observed during follow-up.
- The standardized pain and function scores at 1 and 2 months after treatment between 2 groups were similar but the scores of the cell treatment group were significantly better than those of the control group at 3 and 6 months.
Conclusion: Human umbilical cord stem cells can significantly improve the joint function and quality of life for patients with degenerative knee osteoarthritis. It takes effect after 1 month and the treatment effect can be sustained for 6 months.
A December 2018 study in the medical journal Stem cells translational medicine (11) examined single versus multiple umbilical cord blood stem cell treatments in patients suffering from knee osteoarthritis.
The patients in this study either:
- Received hyaluronic acid injections at the baseline of the study and at 6 months.
- Received a single-dose umbilical cord blood stem cell treatment at baseline.
- Received two umbilical cord blood stem cell treatments at baseline and 6 months.
- Clinical scores and magnetic resonance images (MRIs) were assessed throughout the 12 months follow-up.
- No severe adverse events were reported.
- Only umbilical cord blood stem cell treatment patients experienced significant pain and function improvements from baseline.
- Patients reached significantly lower levels of pain in the two umbilical cord blood stem cell treatment group as compared with the hyaluronic acid injection group.
- Repeated umbilical cord blood stem cell treatment is safe and superior to hyaluronic acid injections in knee osteoarthritis at 1-year follow-up.
There is a controversy surrounding umbilical cord blood stem cells therapy offered in the United States. The controversy surrounds the makeup of the injectable solution. There are those in the medical community who insist that the injectable solution contains beneficial and abundant live umbilical cord blood stem cells. There are those who suggest that there were no live umbilical cord blood stem cells in the injectable solution. As of the time this question remains debated. I have tried this treatment on myself, and, on numerous occasions. Once satisfied that I was personally attaining good results, our office slowly began offering it to our patients. We monitored and noted the empirical, observational evidence and found that this treatment would be effective for certain patients. We can report at this time, with confidence, that this treatment is helping people.
Adipose (Fat derived) stem cells for knee osteoarthritis
There are numerous studies on the benefit of adipose derived stem cells for knee osteoarthritis. It is for some an effective treatment. Most of the emails we get from people asking us about the difference between adipose derived stem cells and bone marrow derived stem cells are looking for that definitive edge in which treatment they should choose.
In our office we do not use adipose stem cells. A primary reason is the liposuction procedure needed to harvest the stem cells. We are also not convinced that adipose stem cells work better than bone marrow derived stem cells. So three important factors in our decision are extra expense, discomfort of the lipo cell harvest, no clear or definitive benefit of the adipose procedure.
- Doctors at Colorado State University wrote in the Journal of orthopaedic research of how patients saw a greater improvement with bone marrow-derived mesenchymal stem cells when compared to adipose-derived (fat) stromal vascular fraction and placebo treatment.(5)
- Doctors in Taiwan noted that: Mesenchymal stem cells (MSCs) isolated from either bone marrow or adipose tissue show considerable promise for use in cartilage repair. . . MSCs can directly differentiate into chondrocytes (cartilage building cells). . . hey also have immunosuppressive and anti-inflammatory paracrine effects. (They change the joint environment from breakdown to healing by telling the other cells to start repairing.) (6)
The experience factor
This article was prepared to be a jump start of where to follow up to get more research on comparing one stem cell treatment against another. One of the factors rarely, if ever highlighted in research is the experience of the physician in offering these treatments. At the time of this writing, we perform 100 stem cell procedures a month.
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1. Emadedin M, Labibzadeh N, Liastani MG, Karimi A, Jaroughi N, Bolurieh T, Hosseini SE, Baharvand H, Aghdami N. Intra-articular implantation of autologous bone marrow-derived mesenchymal stromal cells to treat knee osteoarthritis: a randomized, triple-blind, placebo-controlled phase 1/2 clinical trial. Cytotherapy. 2018 Oct 11. pii: S1465-3249(18)30605-4.
doi: 10.1016/j.jcyt.2018.08.005. PubMed PMID: 30318332.
2. Burke J, Hunter M, Kolhe R, Isales C, Hamrick M, Fulzele S. Therapeutic potential of mesenchymal stem cell based therapy for osteoarthritis. Clinical and Translational Medicine. 2016;5:27. doi:10.1186/s40169-016-0112-7.
3. Zhang Q, Chen Y, Wang Q, Fang C, Sun Y, Yuan T, Wang Y, Bao R, Zhao N. Effect of bone marrow-derived stem cells on chondrocytes from patients with osteoarthritis. Mol Med Rep. 2016 Feb;13(2):1795-800. doi: 10.3892/mmr.2015.4720. Epub 2015 Dec 28.
4. Emadedin M, Aghdami N, Taghiyar L, Fazeli R, Moghadasali R, Jahangir S, Farjad R, Baghaban Eslaminejad M. Intra-articular injection of autologous mesenchymal stem cells in six patients with knee osteoarthritis. Arch Iran Med. 2012 Jul;15(7):422-8.
5 Kurtzberg J, Lyerly AD, Sugarman J. Untying the Gordian knot: policies, practices, and ethical issues related to banking of umbilical cord blood. J Clin Invest. 2005;115(10):2592-7.
6 Kurtzberg J. Update on umbilical cord blood transplantation. Curr Opin Pediatr. 2009;21(1):22-9.
7. Frisbie, DD, Kisiday, JD, Kawcak, CE, Werpy, NM, McIlwraith, C. Evaluation of adipose-derived stromal vascular fraction or bone marrow-derived mesenchymal stem cells for treatment of osteoarthritis. J Orthop Res. 2009;27:1675–1680.
8 Chang YH, Liu HW, Wu KC, Ding DC. Mesenchymal stem cells and their clinical applications in osteoarthritis. Cell Transplant. 2015 Dec 18.
9 McIntyre JA, Jones IA, Danilkovich A, Vangsness Jr CT. The placenta: applications in orthopaedic sports medicine. The American journal of sports medicine. 2018 Jan;46(1):234-47.
There is controversy in the medical community about umbilical cord blood stem cells. Some insist that the injectable solution contains abundant live umbilical cord blood stem cells. Some suggest that the stem cells are not alive. I have seen the flow cytometry showing live stem cells. The research shows that these stem cells release cytokines and growth factors that awaken native stem cells. I have tried this treatment on myself for both shoulders and knees. After great success, I started using this treatment on patients. I still use PRP and bone marrow depending on the patient’s pathology and requirements. To date the results are excellent for all of these treatments. We are in the process of doing a study on cord blood stem cells (we have done others on bone marrow and PRP) to see which treatments are the most successful. We are awaiting more long term results.