Jimmy was a teenage baseball player with a history of severe abdominal pain. I think his case illustrates how many M.D.’s have lost our ability to structurally diagnose patients with chronic pain. Since he had high abdominal pain below the ribs, he had the million dollar GI work-up for his abdominal pain. He was ultimately placed on very high dose narcotics and other drugs by a local Childern’s hospital. When he first came to our clinic, his pain was across the top of his stomach and he couldn’t sleep more than 1-2 hours a night. He wasn’t eating well and had given up baseball (his passion). What was striking on initial exam was that if this patient had an internal organ problem, you wouldn’t expect his upper abdomen to be tender, right along the rib cage. When these lower ribs were followed to his upper back, he had muscle spasms in this area as well. Since nobody had ever found anything wrong with little Jimmy’s internal organs, it was a safe bet that he had a lower thoracic problem leading to pain in the ribs, which masqueraded as a stomach problem. Further exam in Jimmy’s case showed that the abdominal muscles had significant trigger points and the area that attached to the ribs had a significant enthesopathy (swelling at the tendons that attach to bone, due to excessive pulling on the attachment by tight muscles). Our plan was to begin injecting the lower ribs with prolotherapy solution to allow these abdominal muscle attachments to heal and to get rid of trigger points in the abdominal and upper back muscles using an IMS technique. Within 12 weeks (Jimmy had suffered for two years), Jimmy was back to playing baseball and without pain. He went off all meds and at one year follow-up, he’s still off meds and without pain. His case is a good example of how a simple musculosketal pain problem can be misdiagnosed, cost a bunch of money in expensive diagnostic work-up, and if undiagnosed and without proper treatment, would have led to a teenager addicted to narcotics.
Are your adult stem cells drugs? The FDA has been sparring with physicians and patients over this issue. Today a patient group registered it’s opposition to this FDA stem cell position. For a real dose of reality about how good you have it, check out the “Patient Voices” section of this site. These are people with terminal illness who are dying. This whole debate started with the FDA’s position that the minimal stem cell culture process of the Regenexx procedure should be classified as a drug. Why? No real specifics give, it seems to be a “cause I said so” issue. This lead to physicians organizing to regulate themselves so that patients can have access to safe adult stem cell therapy now. Where is all of this going? Adult stem cells processed with minimal culture techniques aren’t drugs, I suspect the best quote is from a physician from Ft. Meyers Florida who recently joined The American Stem Cell Therapy Association (ASCTA), “This is a patient physician situation and the FDA needs to stay out.I commend all of you for starting this.” Enough siad.
As you may recall, the International Society of Stem Cell Researchers (ISSCR) released their new guidelines in response to many “off-shore” stem cell companies offering unknown origin “stem cells” to treat just about any illness. I was happy to see these guidelines. We think it’s important to compare the Regenexx Procedure to these guidelines. To make these easier to follow, the guidelines have been paraphrased.
Stem cells from other people are more risky and need to be more closely monitored. The Regenexx procedure only uses autologous mesenchymal stem cells (MSC’s). This means that the stem cells that are used are only from the same patient. Research would suggest that stem cells from a donor may carry a genetic disease transmission risk. This means that cells from the bone marrow of another patient with osteoporosis may transmit that genetic disease to another patient.
The use of animal components to grow cells must be replaced by human or non-animal components. Stem cells are commonly cultured in Fetal Calf Serum. With the infectious risks associated with FCS (for example, mad cow disease), FCS is not appropriate for human use. As a result, the Regenexx procedure (using a patent pending procedure) grows the patient’s stem cells in the natural growth factors obtained from the patient’s own blood platelets.
Adverse changes to cells during culture must be minimized. In research, stem cells are often tricked into growing for extended periods. This can cause problems to develop in the cells, which can lead to the possibility of tumor formation. Extensive medical research has shown that MSC’s can be grown for about 5-6 weeks before they show signs of problems. We take a more conservative stance, that cells should only usually be grown for a maximum of 10-20 days.
The level of oversight of stem cell therapy should be proportional to the risk. Stem cells from someone else’s body (allogeneic) should be scrutinized more closely than autologous (from the same person). Stem cells that are embryonic or cord blood in origin should also be considered to have more risk than adult stem cells. In addition, cells that are either heavily modified or manipulated (for example stem cells with changes to their genes) are more risky than cells that have been minimally manipulated. Finally, stem cells, which perform a certain function in the body, that are used to perform a different function in therapy (non-homologous) are more risky than homologous (stem cells that usually repair cartilage being used to repair cartilage). The Regenexx procedure takes the safest route on all of this issues-we use only autologous, adult origin, minimally manipulated, and homologous cells.
Cells should be handled with adherence to set industry guidelines. The Regenexx procedure lab undergoes voluntary annual or biannual audits by Reglera, a leader in the cell culture standards industry. We follow all cGTP guidelines.
Cell banking should have high standards. We offer patients the ability to freeze and store cells that are not being used for an active procedure. Rather than rely on the industry standard of liquid nitrogen storage, we have decided on the more expensive and higher standard of dry phase storage. Our rationale is that recent research questions whether viruses may be transmitted between patient’s samples via liquid nitrogen.
Successful animal models are needed before stem cell therapy can be tried in humans. The Regenexx procedure uses only successful animal models before considering a treatment trial in human patients. For example, animal data must exist on the use of MSC’s for a specific application (like cartilage or tendon repair) before we will consider adding that disease to be treated. In addition, each new application for the procedure goes through a trial test period in an IRB approved study. Clinic physicians then use 3.0T MRI, exam, and patient reporting to decide if the procedure is working before releasing that treatment for commercial patients.
Large animal models need to be used for tissue repair studies such as tendon, bone, or cartilage. Regenerative Sciences spent a year porting a large animal model treatment to a human model. The large animal model had proved successful before we considered moving the procedure to a human model.
The cell line chosen for the therapy must first be shown not to be toxic or have adverse effects in the test tube or in animal models. We chose MSC’s because as of 2009 there are more than 7,000 published articles on this cell line. MSC’s are the most extensively researched of almost any stem cell line and known in animal models (as we deploy them) not to be toxic or associated with significant adverse outcomes.
The risk of stem cell lines causing tumors must be accessed. We have already submitted early safety data for publication and maintain an extensive tracking database to rule out that stem cells from the Regenexx procedure are causing tumors. As of early 2009 this tracking database had 300 patients, with 600 expected by the end of 2009. No tumorogenicity has been observed.
Animal models should exist which allow the clinician to determine the response of the stem cells to drugs the patient may be taking. The reason we chose the MSC stem cell line was the fact that so much data has been collected in animal models. We have many papers on the effects of everything from NSAID’s to obscure drugs on MSC’s. In addition, we have extensive clinical culture experience and have developed our own database of drugs that will reduce stem cell yield. Finally, we council our patients to get off of all possible prescription and non-prescription drugs prior to the procedure.
All studies performed using stem cells should have a multidisciplinary review board to oversee human safety. The Regenexx procedure was developed under the auspices of a department of Health and Human Safety registered Institutional Review Board.
The stem cell based therapy must offer a clinical advantage over existing therapies. The Regenexx procedure offers a lower risk option over traditional surgical options, which produce more tissue trauma, more downtime, more risk for infection or surgical adverse events.
Patient monitoring and adverse event reporting are key components of stem cell therapy. As discussed above, we maintain a comprehensive complications and outcomes tracking database with regular patient contacts.
The clinical outcomes (both good and bad) must be published in peer reviewed medical journals. We at RSI have already published imaging based case reports and are now moving onto clinical case series and safety studies. We are currently preparing for publication larger case series and will eventually move onto to randomized controlled placebo trials.
In 2005-2006 we mixed up BMAC in our cell biology lab. It was easy to create from a marrow aspirate. We performed some basic MRI studies with pre and post 3.0T high field studies and ran outcome questionnaires for knee and hip arthritis patients. We were unimpressed by the results and because of this experience moved on to culture expanded mesenchymal stem cells.
BMAC has become popular of late. In this procedure, a physician takes a bone marrow aspirate, places it in a specially designed centrifuge and pulls out a concentrate of bone marrow nucleated cells. This has been billed as a stem cell concentrate, but the stem cells that are concentrated in reasonable numbers tend to be CD34+ heme progenitors (stem cells that make new blood) and not MSC’s (Mesenchymal Stem Cells). Since MSC’s are the MVP of the adult stem cell mix available in a bone marrow concentrate, their concentration is very important to the success of such a treatment. A recent study on bedside bone marrow concentrate machines for MSC’s (BMAC) determined what concentrations were possible from a commercially available centrifuge unit. Using this study to calculate MSC numbers, a 60 ml bone marrow draw would produce 70,000-90,000 MSC’s. The Regenexx procedure yields after culture expansion are in the 5M-100M range. Based on this data, the Regenexx procedure produces approximately 100-1,000 times more cells than you can obtain with BMAC bedside systems. Based on this and other data, our best estimate is that the average micro fracture procedure would release 5-10 ml of un-concentrated marrow, so about 500-1,000 MSC’s into the defect site. Our own dosing data and the copious animal research would suggest that for appropriate cartilage, tendon, ligament, muscle repair the necessary MSC dose is in the millions range. Obtaining that amount of MSC’s from a BMAC system would require unacceptably high volumes of whole marrow from the patient. The conclusion, while very convienent, BMAC doesn’t have the right stuff.
For more information on different stem cell types, I’ve posted a video below:
A doctor discusses ACL Laxity and Knee Braces. The ACL is the duct tape in the knee that holds the big thigh bone (femur) to the leg bone (tibia). It stabilizes (along with the PCL) the knee in a front-back direction. A knee brace can be used to help the ACL. An ACL knee brace allows the knee to flex and extend while holding the thigh and leg bones in alignment. However,is there a better way than wearing a knee brace all the time? Knee surgeries to replace or reconstruct the ACL should only be performed (in my opinion) if the ACL is completely gone. if the ACL is just lax, an older method of treatment is prolotherapy. This is the injection of a substance to tighten the ligament. Reeves has shown that the ligament can be tightened in this way using monthly shots for about 6 months. Newer options already being performed in the US include seeding the patient’s own adult stem cells onto the ACL ligament to repair the damage. This only works if there are ACL fibers left to seed. Eventually, this same technique may be used to inject an ACL scaffold material into the knee with adult stem cells that can create a ligament. So if you have a stretched ACL and you’re using a knee brace for ACL laxity, investigate some of the injections that can help you loose the brace!
As a doctor, I get asked allot, “Does ibruprofen inhibit ligament repair?“. In short, likely. We know from the medical research that Ibuprofen belongs to a drug class (NSAID’s) that inhibits the cyclo-oxengenase pathway of inflammation (COX) and that this can inhibit bone healing. We also know from animal models that injecting NSAID’s into a joint can cause arthritis. We also know that NSAID’s can negatively impact adult mesenchymal stem cells that are key in the ligament healing process. The upshot, Ibuprofen and NSAID drugs like Alleve, Motrin, Celebrex, and others likely impair healing of bones, ligaments, tendons, and other musculoskeletal tissues by impairing adult stem cells in their normal role of tissue repair. The upshot, based on the circumstantial evidence, taking NSAID’s after a ligament injury is likely a bad idea.
So you’ve torn your rotator cuff, is there such a thing as rotator cuff pain relief therapy without surgery? Yes. First the simple stuff. If you can’t lift your arm, then you’re likely too injured for this particular blog post (more to come). However, if you just have pain on lifting, then this blog’s for you. If you’re in this later category, the good news is that you likely have a partial rotator cuff tear, where the muscle is torn, but not through and through. We frequently use treatment such as IMS to get rid of the muscle knots and help the pain. This is where a tiny acupuncture needle is used to eliminate painful portions of the muscle (this is very different than traditional Chineese acupuncture where the muscles aren’t treated). In addition, massage therapy of the supraspinatus, infraspinatus, subscapularis, teres, or upper trapezius may help. Finally, before you consider surgery, look at one of the newer injection based options to heal the tear with less down time. For example, the patient’s own stem cells can now be injected into the rotator cuff tear under x-ray guidance, so that no surgery is required. This gets rid of that big blue pillow immobilizer and the long recovery commonly associated with rotator cuff surgery. You should give your rotator cuff tear a 4-6 weeks to heal and if it’s staying the same, time to get something done. The big issue you want to avoid is muscle atrophy, so all of this should be performed with rotator cuff exercises.
The rotator cuff provides stability to the shoulder. The most commonly injured muscle of the four muscles that make up the “rotator cuff” (Supraspinatus, Infraspinatus, Teres, Subscapularis) is the supraspinatus. Exercises that stress the rotator cuffwould focus on use of these four muscles more than other surrounding shoulder muscles (like the trapezius). To stress the supraspinatus, the empty can maneuver is the best way to go. Place your arm out to the side with the thumb down like you’re pouring out a can of soda. The arm should be slightly forward. If you move your arm up and down from the side of your body to just shoulder level, the muscle being stressed is the supraspinatus. If this is painful and if when you place the thumb up much of the pain goes away, that’s a good indication that your supraspinatus muscle may be torn or injured. If you can’t do this at all, it may be completely torn and retracted (not connected). The infraspinatus and teres can be stressed by movements that externally roate the shoulder and arm (if you place your elbow at your side and start with your hand on your stomach and move it out to the side while keeping your elbow tucked in, that’s external rotation). The subscapularis goes the other way, it brings the hand in with the elbow tucked into the side. What if exercises won’t heal the problems? You might consider some of the newer non-surgical methods that use injections of thepatient’s own stem cells to heal the rotator cuff tear. The recovery times are much shorter and you can avoid the knife!
A pain doctor expert discusses how to fix low back disks without surgery. The tear in the disk must be repaired. The concept of disc repair is discussed and a video referenced.
