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!



(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).

(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).

(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

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Chris Centeno, MD is a specialist in regenerative medicine and the new field of Interventional Orthopedics. Centeno pioneered orthopedic stem cell procedures in 2005 and is responsible for a large amount of the published research on stem cell use for orthopedic applications. View Profile

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