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You can’t open a newspaper or hit Google or Facebook without seeing an ad for stem cells for knees. The ads discuss how stem cell injections can basically regrow you new knees if yours are worn out with arthritis. Is this true? Let’s dig in.

Why Stem Cells for Knees?

If you have moderate or severe knee arthritis you are likely a knee replacement candidate. Based on research performed in the early 2000s, it was estimated that approximately 700,000 knee replacement surgeries happened each year in the United States (1). This already very high number was expected to balloon to roughly three and a half million knee replacements annually by the year 2030!

Knee replacement involves the amputation of the arthritic joint and the surgical placement of a knee replacement prosthesis. The complications are pretty substantial and can include death, blood clots behind the knee or in the lungs, infection of the joint, a heart attack, a serious stroke, and more pain than you had before the surgery (2). Hence, this is not a small surgery but instead a major surgical endeavor.

You would think that we have loads of research showing that knee replacement is VERY effective. However, you might be very surprised to learn that a large study showed that in many younger and more active patients the procedure had less efficacy (3). There were better outcomes in patients who were older and in more pain. Meaning if they couldn’t walk the mall because of pain they did well, but if they were in pain from a 20-mile bike ride they tended to be dissatisfied with the results. To learn more about the research on knee replacement, check out my video below:

maxresdefault - Stem Cells for Knees?

Hence, the concept of stem cells for knees is that a minimally invasive injection could help stall the need for big knee surgery or get rid of the need for knee replacement altogether. Is there any research that shows that this is possible?

Do Stem Cells for Knees Work as Advertised?

Our clinic was the first in the world to inject stem cells into a knee joint to treat arthritis. That was way back in 2005. However, in the last several years we’ve seen an explosion of poorly trained providers offering these therapies and promising results that aren’t real. Let me explain.

So what’s real and what’s fiction? Let’s look at what the science says. The first published research studies on stem cells for knees were performed by our group using bone marrow stem cells taken from the same patient in which they were used (4,5). These results were solid and even demonstrated some MRI improvement in cartilage lesions and the size of degenerated meniscus tissue.

Our clinic then published several more studies showing that using a same-day bone marrow concentrate produced good results. While our first research patients were treated with cells that were grown to bigger numbers in the lab, these patients were treated with the stem cell fraction taken from their own bone marrow (6,7). We have since performed a high-level randomized controlled trial using our unique stem cell protocol to treat for knee arthritis showing better results than physical therapy (8). This is significant, as a recent randomized trial of knee replacement showed that the invasive procedure barely beat the results that physical therapy offered (19).

Other clinics and medical schools have produced research showing promising results for stem cells for knees. For example, a recent study on the Lipogems fat system demonstrated that it worked about the same as bone marrow concentrate (9). In addition, there are other stem cell procedures (like bone marrow cells that are grown in a lab) that have also shown promise in treating knee osteoarthritis (10-12).  However, none of these treatments where stem cells are grown to bigger numbers have US FDA approval.

In summary, there is mounting evidence that certain stem cell treatments for knee arthritis may help pain and function for patients who otherwise would need a knee replacement. Now let’s dive into the different types out there.

Are There Different Kinds of Stem Cell Procedures for Knees?

There are two main stem cell procedures types that are commonly used to treat knee arthritis: autologous and allogeneic. Autologous is a term that means using your own cells to treat your knee. The two most common autologous stem cell procedures used to treat knee arthritis are either derived from bone marrow or fat.

Autologous

Bone marrow concentrate is by far the most popular type of knee stem cell treatment. This procedure begins with the doctor taking a sample of bone marrow aspirate from the back of the hip area (PSIS). The sample is then placed in a specialized centrifuge to isolate and then extract the stem cell fraction of the bone marrow. The product that’s produced is called Bone Marrow Concentrate (BMC) or Bone Marrow Aspirate Concentrate (BMAC). Be careful here, as we have seen some clinics cut corners by skipping the critical centrifuge concentration step because it’s easier for the doctor. However, this short cut dramatically reduces the number of stem cells your doctor will have available for your injection.

Fat is another common procedure used to treat knee arthritis. In this procedure, liposuction is used to get adipose tissue. In the United States, there is a procedure called Lipogems that breaks the fat down into micronized pieces. This is also called a Mfat or a Micro-fat procedure. There is some new research demonstrating that this procedure can help patients with knee arthritis (9).

There is another fat-based procedure called “SVF” which stands for Stromal Vascular Fraction (22). This begins the same as a Lipogems procedure but then digests the fat using an enzyme. Why do this? The fat in a Lipogems procedure has stem cells encased in collagen so the stem cells aren’t freely available. However, disgesting the collagen breaks them open out of their collagen prisons. However, please note that as of this writing, this procedure is NOT legal in the US, even though many clinics offer it. Hence, please don’t sign up for this procedure due to issues with the feds.

Allogeneic

Allogeneic means that the stem cells are from a donor. A very common source of “stem cells” being offered right now is birth tissues. The most common treatments here are those that are derived from umbilical cords or amniotic tissue. Why did I put the term stem cells in quotes above? Several studies have now been performed on the commercially available stem cell products used by clinics offering amniotic and umbilical cord “stem cell” treatments. Three university labs and our lab at the Centeno-Schultz Clinic have all confirmed that there are no living cells in these products, let alone living stem cells (16-18).

How is it possible that these clinics can advertise these therapies as having many stem cells? Check out this piece by ProPublica on the topic. It’s an eye-opener. 

Can Your Stem Cells Repair Your Knee Cartilage?

This is the million-dollar question, right? You’ve been told that your problem is that you have lost cartilage in your knee, so stem cells should be able to grow that back, right? The real answer, outside of all the seminar hype, is “maybe”.

First, in some patients with smaller holes in the knee cartilage, also called a chondral or osteochondral lesion, you can expect some healing from a properly delivered stem cell treatment. Our clinic and others have published research papers showing cartilage improvement on MRI (4,5,13). Having said that, not everyone responds in this way.

The next most obvious questions here are about what patients with more severe knee arthritis can expect and this is where the answers get a bit fuzzier. For example, if you have some cartilage remaining in your arthritic knee, can stem cell injections make that cartilage better? Yes, that can happen. For instance, several research papers in real-world patients have shown better cartilage quality from the injection or surgical placement of Mfat and bone marrow concentrate (14,15).

The most common question I get is whether knee stem cell injections can regrow lots of lost cartilage in arthritic knees that are “bone on bone”? Regrettably, the answer to this common question is a firm “No”. There is no credible research published by our clinic or others that has shown this is possible. Now, despite this not happening, we still see good results in patients with “bone on bone” arthritis. Why?

If the procedure is not regrowing lost of cartilage in severely arthritic knees, how does the procedure help patients? Lots of ways. The first is taking a painful and pro-breakdown witches brew of destructive chemicals and turning that into a positive pro-repair environment (23). Another is by the stem cells giving their good batteries (mitochondria) to cartilage and other cells that have bad batteries (20). Stem cells can also deactivate bad “Pac Man” (macrophage) cells that eat cartilage (21).

I created a video to highlight some of the before and after cartilage repair (and other effects) that we have seen in the last decade and a half:

maxresdefault - Stem Cells for Knees?

Is Stem Cell Treatment for Knees Covered by Major Insurance Plans, Medicare, Or Medicaid?

Regrettably, there is no insurance coverage for this knee stem cell therapy. The company we founded, called Regenexx, has gotten self-funded health plans (insurers who pay for their own medical care rather than using an insurance company) to cover these procedures. They have millions of covered lives to date.

How Long Does Knee Stem Cell Therapy Last?

Based on our research, knee stem cell procedures work for about 70% of patients. Of those patients, these procedures can last for 2-7 years, The procedure then often needs to be redone.

Knee Stem Cell Therapy Cost?

The cost for these treatments can be as little as a few thousand dollars to 8-10 thousand dollars. You usually get what you pay for, meaning cheaper procedures are usually performed by non-physicians with little expertise about how to do this right.

The upshot? Knee stem cell procedures are an up and coming way to avoid knee surgery or replacement. However, doing your homework is critical!

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References:

(1) Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am. 2007 Apr;89(4):780-5. DOI: 10.2106/JBJS.F.00222

(2) Healy WL, Della Valle CJ, Iorio R, et al. Complications of total knee arthroplasty: standardized list and definitions of the Knee Society. Clin Orthop Relat Res. 2013;471(1):215–220. doi:10.1007/s11999-012-2489-y

(3) Ferket Bart S, Feldman Zachary, Zhou Jing, Oei Edwin H, Bierma-Zeinstra Sita M A, Mazumdar Madhu et al. Impact of total knee replacement practice: cost effectiveness analysis of data from the Osteoarthritis Initiative BMJ 2017; 356 :j1131 doi: https://doi.org/10.1136/bmj.j1131

(4) Centeno CJ1, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Regeneration of meniscus cartilage in a knee treated with percutaneously implanted autologous mesenchymal stem cells. Med Hypotheses. 2008 Dec;71(6):900-8. doi: 10.1016/j.mehy.2008.06.042 

(5) Centeno CJ, Busse D, Kisiday J, Keohan C, Freeman M, Karli D. Increased knee cartilage volume in degenerative joint disease using percutaneously implanted, autologous mesenchymal stem cells. Pain Physician. 2008 May-Jun;11(3):343-53. https://www.ncbi.nlm.nih.gov/pubmed/18523506

(6) Centeno C, Pitts J, Al-Sayegh H, Freeman M. Efficacy of autologous bone marrow concentrate for knee osteoarthritis with and without adipose graft. Biomed Res Int. 2014;2014:370621. doi:10.1155/2014/370621

(7) Centeno CJ, Al-Sayegh H, Bashir J, Goodyear S, Freeman MD. A dose response analysis of a specific bone marrow concentrate treatment protocol for knee osteoarthritis. BMC Musculoskelet Disord. 2015;16:258. Published 2015 Sep 18. doi:10.1186/s12891-015-0714-z

(8) Centeno C, Sheinkop M, Dodson E, et al. A specific protocol of autologous bone marrow concentrate and platelet products versus exercise therapy for symptomatic knee osteoarthritis: a randomized controlled trial with 2 year follow-up. J Transl Med. 2018;16(1):355. Published 2018 Dec 13. doi:10.1186/s12967-018-1736-8

(9) Mautner K1 Bowers R, Easley K, Fausel Z, Robinson R. Functional Outcomes Following Microfragmented Adipose Tissue Versus Bone Marrow Aspirate Concentrate Injections for Symptomatic Knee Osteoarthritis. Stem Cells Transl Med. 2019 Jul 21. doi: 10.1002/sctm.18-0285.

(10) 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;20(10):1238-1246. doi: 10.1016/j.jcyt.2018.08.005.

(11) Lee WS, Kim HJ, Kim KI, Kim GB, Jin W. Intra-Articular Injection of Autologous Adipose Tissue-Derived Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis: A Phase IIb, Randomized, Placebo-Controlled Clinical Trial. Stem Cells Transl Med. 2019;8(6):504–511. doi:10.1002/sctm.18-0122

(12) Chahal J, Gómez-Aristizábal A, Shestopaloff K, et al. Bone Marrow Mesenchymal Stromal Cell Treatment in Patients with Osteoarthritis Results in Overall Improvement in Pain and Symptoms and Reduces Synovial Inflammation. Stem Cells Transl Med. 2019;8(8):746–757. doi:10.1002/sctm.18-0183

(13) Vangsness CT Jr, Farr J, Boyd J, Dellaero DT, Mills CR, LeRoux-Williams M. Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study. J Bone Joint Surg Am. 2014 Jan 15;96(2):90-8. doi: 10.2106/JBJS.M.00058.

(14) Krych AJ, Nawabi DH, Farshad-Amacker NA, Jones KJ, Maak TG, Potter HG, Williams RJ. Bone Marrow Concentrate Improves Early Cartilage Phase Maturation of a Scaffold Plug in the Knee: A Comparative Magnetic Resonance Imaging Analysis to Platelet-Rich Plasma and Control. Am J Sports Med. 2016 Jan;44(1):91-8. doi: 10.1177/0363546515609597.

(15) Hudetz D, Borić I, Rod E, et al. The Effect of Intra-articular Injection of Autologous Microfragmented Fat Tissue on Proteoglycan Synthesis in Patients with Knee Osteoarthritis. Genes (Basel). 2017;8(10):270. Published 2017 Oct 13. doi:10.3390/genes8100270

(16) Panero, A, Hirahara, A., Andersen, W, Rothenberg J, Fierro, F. Are Amniotic Fluid Products Stem Cell Therapies? A Study of Amniotic Fluid Preparations for Mesenchymal Stem Cells With Bone Marrow Comparison. The American Journal of Sports Medicine, 2019 47(5), 1230–1235. https://doi.org/10.1177/0363546519829034(

17) Becktell L, Matuska A, Hon S, Delco M, Cole B, Fortier L. Proteomic analysis and cell viability of nine amnion-derived biologics. Orthopedic Research Society Annual Meeting, New Orleans, 2018. https://app.box.com/s/vcx7uw17gupg9ki06i57lno1tbjmzwaf

(18) Berger D, Lyons N, Steinmetz, N. In Vitro Evaluation of Injectable, Placental Tissue-Derived Products for Interventional Orthopedics. Interventional Orthopedics Foundation Annual Meeting. Denver, 2015. https://interventionalorthopedics.org/wp-content/uploads/2017/08/AmnioProducts-Poster.pdf

(19) Skou ST, Roos EM, Laursen MB, Rathleff MS, Arendt-Nielsen L, Simonsen O, Rasmussen S. A Randomized, Controlled Trial of Total Knee Replacement. N Engl J Med. 2015 Oct 22;373(17):1597-606. doi: 10.1056/NEJMoa1505467.

(20) Ahmad T, Mukherjee S, Pattnaik B, et al. Miro1 regulates intercellular mitochondrial transport & enhances mesenchymal stem cell rescue efficacy. EMBO J. 2014;33(9):994–1010. doi:10.1002/embj.201386030

(21) van Lent PL, van den Berg WB. Mesenchymal stem cell therapy in osteoarthritis: advanced tissue repair or intervention with smouldering synovial activation?. Arthritis Res Ther. 2013;15(2):112. Published 2013 Mar 20. doi:10.1186/ar4190

(22) Bora P, Majumdar AS. Adipose tissue-derived stromal vascular fraction in regenerative medicine: a brief review on biology and translation. Stem Cell Res Ther. 2017;8(1):145. Published 2017 Jun 15. doi:10.1186/s13287-017-0598-y

(23) Barry F, Murphy M. Mesenchymal stem cells in joint disease and repair. Nat Rev Rheumatol. 2013 Oct;9(10):584-94. doi: 10.1038/nrrheum.2013.109.