Ask Dr. C – Episode 4

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I love getting all of these questions to answer in more depth, so here’s another episode of Ask Dr. C! Today we’ll cover diets to improve stem cell function, using BMP-2 for cartilage repair, and single vs. multiple PRP shots to treat knee arthritis. Let’s dig in.

4 years ago had a successful platelet lysate procedure and Recently had SD stem cell injections by regenexx in two lumbar discs. Any comments on intermittent fasting and or ketogenic diets impacting stem cells function? Also had my blood panel done and the recommendations included some vitamin D, K2, and some testosterone supplementation. Any data or comments to optimize probability of successful outcome.

Intermittent fasting and ketogenic diets are great topics and ones that we bring up quite a bit. Stem cells, just like all of your cells, get hurt by blood sugar that isn’t in tight control. Hence, we believe that patients who have metabolic syndromes that involve poor blood sugar control may be harming their own adult stem cells. For example, researchers have found damage to the stem cells of patients with blood sugar problems (1). One way to help control blood sugar is intermittent fasting or a ketogenic diet. Hence, we often recommend one or the other if you’ve got blood sugar control problems (are pre-diabetic or have type II diabetes). In addition, intermittent fasting has been shown to improve stem cell function (2).

We tested testosterone supplementation for stem cells many years ago and looked at bone marrow stem cell function. Regrettably, it didn’t help the cells in any way that we could discern. To learn more, see my video below:

This is an amalgam of a few questions on the same topic: Does BMP-2 help cartilage repair and should Regenexx be considering it for use?

Every few months, there’s another paper on some drug or cytokine that can help cartilage repair in animals. The problem is that nobody knows if this works in humans. Recently a very interesting paper came out that suggested that a growth factor called Bone Morphogenic Protein-2 (BMP-2) helped cartilage repair in mice that had a microfracture procedure (3).

This is certainly a promising development for two reasons. One is that like many different growth factors and cytokines, BMP-2 helps cartilage repair. However, perhaps most importantly is that this growth factor is actually commercially available as a drug sold by Medtronic and is called Infuse. Let’s dive in there a bit.

Infuse is FDA approved to enhance the likelihood of a low back fusion during spine surgery. The idea is that since BMP-2 is like a super quadruple espresso shot for bone-forming cells, it should be able to enhance the chance that two vertebrae will fuse together during a fusion surgery. Does it work? Yes. However, it’s had some problems. One of the major problems was growing extra bone in the spine, which could press on spinal nerves or the spinal cord (4). Other concerns included increased cancer rates, infections, and nerve injury. Because of these issues, we would proceed very cautiously before ever using BMP-2 in humans in the knee.

I note some groups suggest multiple PRP injections given a few weeks apart to treat knee arthritis. Do you feel, at anytime; this plan is better then a one shot regimen?

This is a great question. A handful of studies have compared single shot PRP versus multiple shots. First, before we get to that research, we need to get a handle on a big issue in PRP. What one clinic calls PRP and what you get at another clinic also offering PRP is quite different.

One difference is the amount of red and white blood cells in the mix. If there’s a lot of both, the PRP tends to be red, if there’s little of both, it tends to be amber. Studies comparing the two have generally favored the amber PRP.

Then there’s the issue of PRP dose. This is commonly measured as a multiple of the number of platelets in the original blood sample. For example, 2-3X PRP means that the product has 2-3 times as many platelets as in the whole blood. If you’re younger (generally early thirties or less), the dose isn’t as big a deal and the simple machines in doctor’s offices that produce 2-5X PRP will get the job done. However, our research has shown repeatedly that if you’re older, you need higher concentrations of PRP (5). Why?

As we age, the amount of growth factors in each platelet declines. It’s these growth factors that allow platelets to stimulate healing. Hence, by increasing the concentration of the platelets in the PRP into the 7-20X range, we can overcome those lower growth factor levels. There’s just one problem. Most bedside machines used by doctors can’t get to these concentrations. To do that, you need a lab, which is what we require of all of our Regenexx Affiliates.

Hence, now that you know that all PRP is NOT created equal, let’s look at single versus multiple-dose PRP research (6). One study found that multiple PRP injections helped more than a single injection, but only for patients who had mild arthritis. This approach didn’t work if the arthritis was severe. A larger study that looked at many studies on PRP dosing and concluded that for the most part, a single PRP injection worked as well as multiple for reducing pain, but the patients that had multiple shots had better functional improvements at 6 months (7). However, they noted that this issue wasn’t yet close to settled and more research was needed.

Given that we use very high dose PRP, which none of these studies could achieve, our experience is that a single shot is usually fine to get great results in the right patients. However, if there’s partial relief, we sometimes use a series of shots.

The upshot? I love getting all of these questions. Please keep them coming as they let me tailor the blog to my readers!

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References:

(1) Kornicka, K., Houston, J. & Marycz, K. Dysfunction of Mesenchymal Stem Cells Isolated from Metabolic Syndrome and Type 2 Diabetic Patients as Result of Oxidative Stress and Autophagy may Limit Their Potential Therapeutic Use. Stem Cell Rev and Rep 14, 337–345 (2018). https://doi.org/10.1007/s12015-018-9809-x

(2) Brandhorst S, Choi IY, Wei M, et al. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015;22(1):86-99. doi:10.1016/j.cmet.2015.05.012

(3) Murphy, M.P., Koepke, L.S., Lopez, M.T. et al. Articular cartilage regeneration by activated skeletal stem cells. Nat Med (2020). https://doi.org/10.1038/s41591-020-1013-2

(4) Epstein NE. Complications due to the use of BMP/INFUSE in spine surgery: The evidence continues to mount. Surg Neurol Int. 2013;4(Suppl 5):S343-S352. Published 2013 Jul 9. doi:10.4103/2152-7806.114813

(5) Berger DR, Centeno CJ, Steinmetz NJ. Platelet lysates from aged donors promote human tenocyte proliferation and migration in a concentration-dependent manner. Bone Joint Res. 2019;8(1):32-40. Published 2019 Feb 2. doi:10.1302/2046-3758.81.BJR-2018-0164.R1

(6) Görmeli G, Görmeli CA, Ataoglu B, Çolak C, Aslantürk O, Ertem K. Multiple PRP injections are more effective than single injections and hyaluronic acid in knees with early osteoarthritis: a randomized, double-blind, placebo-controlled trial. Knee Surg Sports Traumatol Arthrosc. 2017;25(3):958-965. doi:10.1007/s00167-015-3705-6

(7) Vilchez-Cavazos F, Millán-Alanís JM, Blázquez-Saldaña J, et al. Comparison of the Clinical Effectiveness of Single Versus Multiple Injections of Platelet-Rich Plasma in the Treatment of Knee Osteoarthritis: A Systematic Review and Meta-analysis. Orthop J Sports Med. 2019;7(12):2325967119887116. Published 2019 Dec 16. doi:10.1177/2325967119887116

This blog post provides general information to help the reader better understand regenerative medicine, musculoskeletal health, and related subjects. All content provided in this blog, website, or any linked materials, including text, graphics, images, patient profiles, outcomes, and information, are not intended and should not be considered or used as a substitute for medical advice, diagnosis, or treatment. Please always consult with a professional and certified healthcare provider to discuss if a treatment is right for you.

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12 thoughts on “Ask Dr. C – Episode 4

  1. Anthony

    Is there evidence that suggests that stem cells can help regrow cartilage (specifically shoulder labrum) despite the areas lack of blood supply? Are there published studies/imaging on these results?

    1. Chris Centeno, MD Post author

      Shoulder labrum is a more fibrous tissue that’s connected as one piece to the shoulder capsule and capsular ligaments. The lack of blood supply isn’t usually an issue as both PRP and stem cells produce quite a bit of VEGF which can grow new blood vessels. On studies specifically on shoulder labrum, not much is published with imaging yet. However, we use PRP and bone marrow concentrate to successfully treat hundreds of patients a year. This is a good post to review: https://regenexx.com/blog/shoulder-labral-tear-surgery-pros-cons/

  2. Sheree

    Thank you Dr. Centeno for your passion to help others. My question is that my daughter is scheduled for surgery next week September 1. From the MRI it shows a cyclop lesion on her ACL (injury 10 years ago/they used patella to reconstruct) – is the only way to remove is surgery? Also meniscus had a bucket tear that was fixed 10 years ago but now this new MRI shows tear – I want to tell surgeon to leave the meniscus alone – Does your office remove lesion and at the same time do stem cells? – Another question, if one has little meniscus what is the best route to proceed with?

    1. Chris Centeno, MD Post author

      I had responded to the prior post, here is that response: I would have to know more. Happy to jump on a Telemedicine visit to look at the images. Generally, a cyclops lesion means a big piece of abnormal tissue in the middle of the knee near the ACL. Generally, I would say that we can treat ACL retears with grafts due to old surgeries, but this abnormal growth should likely be surgically removed. We don’t recommend partial meniscectomy (which is what they are likely going to do with the bucket handle tear) which is cutting out the torn part, as the research shows that surgery has no benefit. As far as treating with stem cells, we do have sites that could both do the surgery and treat the knee with stem cells.

  3. Harold Sauder

    Hi Dr. My daughter is loosing her hair. She is 32. I see some ads that say stem cell works to keep the hair from falling out. What is you idea to keep hair from falling out? Thanks Have a great day.

    1. Chris Centeno, MD Post author

      There is more research behind PRP for hair loss

  4. Lance Wolrab

    Maybe a question for another blog post: I am retired military and received a notice from Tricare Prime they are now covering PRP injections. I reached out to them to ask about this, and got a canned answer intended to discourage me, not enable me. Typical insurance. Are there experts in this field who can advise covered persons on how to submit these claims for fair reimbursement?

    1. Chris Centeno, MD Post author

      I know they cover it on a case by case basis, but I have yet to hear of anyone who has successfully bill it and get paid.

  5. Marlene Clinton

    6 weeks after a stem cell procedure to my knee should I be having any pain in my knee? First 6 weeks seemed good, a numbing down of the pain I had before, but then 6 weeks later a sharp pain in my knee occurred, came and went very rapidly. I was very active that day, lifting my grandchildren a lot, etc. Can I still be hopeful that much more healing will occur?

    1. Chris Centeno, MD Post author

      Marlene, I would need to know what type of stem cell procedure you had done and which structures were injected.

  6. Chris wetzel

    I am surprised you haven’t commented on the recent NY times article describing research on mice with arthritic knees. They had a microfracture, then some some stem cells injected along with a substance (FDA approved) that cuts the blood supply, which supposedly converts stem cells to cartilage. This sounds like exactly what you have been shooting for knee arthritis

    1. Chris Centeno, MD Post author

      That question was answered on an earlier post. That’s an animal experiment that has similar results to many others. The FDA approved BMP-2 is a pretty dicey drug that used to be used for spine fusion, but less so since serious side effects were detected.

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