A few years ago we picked up on a medical publication that seemed to suggest that injecting mesenchymal stem cells through small bore needles may hurt the stem cells. The theory made some sense, because very thin needles might expose the stem cells to significant shear forces and turbulence that may damage the cells. The problem was that large bore needles used to place stem cells in a knee or shoulder tend to hurt patients more than tiny, thin needles. When looking at the publication more closely, it was clear that the authors had performed some strange machinations to try and replicate in the research lab what a medical provider might do in a clinic while injecting stem cells in a joint to manage arthritis. So we re-ran the experiment with very slow injection of cells and a more accurate representation of how stem cells get injected into joints and found no difference with the less painful thin needles. Since we had conflicting data we remained cautious and tended to stay with slightly bigger needles when injecting knees and shoulders. We just brought on a full-time researcher in the lab, so our research bandwidth has increased. As a result, we just re-performed the same experiment as part of another investigation and low and behold we got the same results-the smaller needles don’t hurt the stem cells. The graph above is from that recent experiment and shows stem cell viability (y axis) with differing needle sizes (x-axis) and shows no significant difference or trend toward less viability with smaller needle sizes. Thus, we will now use the smaller needles that our patients tend to like better. This again brings up again the Regenexx difference, we don’t just follow the directions that come in a kit we bought, we perform the basic research to make sure everyone else’s assumptions are accurate.
I’m busy this week preparing for 4 lectures in the last 2 weeks of April covering Beunos Aires, Florida, Las Vegas, and Pittsburgh. In preparing for one of those lectures and hunting for an interesting picture for a slide, I came across these pictures from the blog of a paraplegic patient who traveled to Europe for stem cell therapy. I thought they were such great examples of some of the problems we see with stem cell therapy, I would quickly blog on the issue. As I have blogged before, a procedure to harvest stem cells from bone marrow needs imaging guidance. This is because the area at the back of the hip where these cells are taken is very tricky. If you’re in exactly the right spot, you get stem cells, if you’re in the wrong spot (where the bone is paper thin and just a quarter of an inch from the right spot) you get blood and not many stem cells. The image on the left of the doctor taking a bone marrow aspirate shows that no imaging guidance was used to confirm where the needle was placed. If you ask pathologists about this issue (the doctors that examine these samples under a microscope for diagnosis), they will tell you this is a big problem-as often they get blood when they should get marrow because the doctor assumed he was in the right spot. Realize again that the stem cells this doctor is interested in are in the marrow . The image on the right is equally concerning. Here the doctor is inserting the cells in the spine of the patient. Knowing the clinic, it’s likely they’re trying to get these cells “intrathecal“, meaning inside the covering of the spinal cord. Again, no imaging is being used to make sure the cells in the stem cell injection are really getting there. This is concerning for a few reasons. The first is that the doctor may not be in the space he thinks he’s accessing (to hit this space being a few millimeters too shallow or deep can mean not getting the cells to the injured area). Even if he’s in that space, he’s got no way of knowing if the cells will ever make it to the injury site, because he has no way of observing where cells will go. Will the cells travel up, down, right, or left? Will they all get stuck in one spot which is nowhere near the lesion? If this injection of stem cells had just used a simple fluoroscopy unit (one can be purchased for about the cost of 3-4 treatments at this center) and some radiographic contrast (which can be seen on x-ray), the doctor could observe that the cells are likely or not likely to make it to the injury site. Obviously, if the cells can’t make it to the area in need of repair, then injecting stem cells may do no good. The upshot? Imaging needs to be used with a marrow aspiration and a stem cell re-injection to make sure that the doctor is actually harvesting the right tissue and re-injecting the cells in the right spot.
Interesting animal model of tendon healing using stem cell injections to help repair Achilles tendon injuries. The Achilles tendon is the large tendon in the back of the ankle, just above the heel. It’s also known as the “heel cord”. It’s the connection between the strong calf muscles and the heel, allowing forceful push off of the foot while walking and running. An Achilles tendon rupture is the most common injury of a tendon. It occurs more commonly in men and is usually seen in younger athletes or middle aged recreational athletes. In addition, the Quinolone family of antibiotics such as Cipro and Levaquin have recently been shown to be a cause of Achilles tendon ruptures. While this problem is commonly treated with surgery, the most modern randomized trials have showed no benefit to surgery. This is important, as Achilles tendon rupture surgery involves extensive downtime and surgical repairs have a high failure rate. To avoid Achilles tendon surgery, the above study sought to determine if the same type of stem cell mix used in Regenexx-SD might help Achilles tendon tears heal. It compared the injection of a bone marrow stem cell mix to cultured mesenchymal stem cells. What was interesting was that the Regenexx-SD type stem cell injection treatment into the Achilles tendon produced better results than the cultured cells. The authors thought this may have been due to the release of certain healing chemicals from the whole cell mix of the Regenexx-SD type therapy (which contains other stem cell types and other cells involved in tendon healing).
The failure of the cultured stem cells in this animal model may have been due to issues that we’ve observed in other research studies. One thing we’ve noticed is that to get enough cells to create a single treatment, it’s common for researchers to pool the cells of several subjects. In addition, the appearance of the stem cells used in these studies often shows that the cultured cells have been grown for too long a time and are under severe stress (not healthy). This may explain why the cultured cells didn’t work as well as fresh cells from a stem cell concentrate. However, the fact that this study confirms an animal model of tendon healing is consistent with results we’ve observed when we inject the stem cells obtained with the Regenexx-SD and Regenexx-C procedures into tendon tears. In addition, any injection based treatment for tendon tears will be significantly less traumatic and usually have a much shorter recovery time than any open surgical treatment.