The Future of Knee and Arthritis Pain
Dennis M. Lox M.D. is an expert in Sports and Regenerative Medicine. Dr. Lox was an early practitioner in sports and stem cell therapy, and this experience has led to a unique perspective on knee pain, arthritis and treatment options. There have been many proposed treatments utilizing stem cell drugs under clinical trials for knee osteoarthritis.
Knee Stem Cell Drug Clinical Trials
One study, which is worth closely looking at, was the Osiris company, a stem cell biotechnology company was in phase 2 clinical trials with its drug stem cell using other people’s stemCells (allogenic stem cells). This drug in clinical trials was called Chondrogen. Chondrogen was initially thought to have great promise, however at the 1 and 2 year followup mark, several problems were noted. The clinical trials were based on a prevailing thought at the time, that more stem cells equated with better results. The research design centered on 50,000,000 versus 150,000,000 stem cell injections into knees versus a placebo injection. Ultimately when the 2 year data was released the research premise that “more was better”, did not hold up, the 50,000,000 Stem cell injection outperformed the 150,000,000 Stem Cell injection.
Chondrogen
Chondrogen was pulled from clinical trials citing research. Design flaws. Many things were learned from the Chondrogen trials. Some patients indeed grew new cartilage after the stem cell injection into their knee.However, the study was based upon ages 18-65 years, injections were given 1 week following Knee arthroscopic meniscus surgery, there were multiple surgeons at different centers doing the surgery, and the placebo was hyaluronic acid, which was also present in the stem cell injection. Hyaluronic acid has a pain relief effect in approximately 1/3 of patients hardly a benign control, much less something inert to place into the stem cell injection. The most troubling finding was that there seems to be a greater percentage of cartilage regrowth in the 50 million dose rather than the 150 million dose. At 2 years, the 150 million Stem Cell dose knee injection was comparable to the placebo injection. This stirred reaction in critics that stem cell injections into knees didn’t work or we were not remotely ready to proceed with knee stem cell injections. The truth lies in just what Osiris Therapeutics said about Chondrogen’s clinical trials, there were design flaws.
Cartilage Regrowth
Any cartilage regrowth after a knee mensisctecomy is significant. Cartilage regrowth in adult knees does not spontaneously happen. There was an approximate 17 % cartilage regrowth noted. If the age range was 18-65 this is not the same patient population. 7 different surgeons performing knee meniscal surgery which was described as complete Medial meniscal debridement is not ideal for a large percentage of regrowth. We know from animal models, regrowth can occur after complete mensicectomy following stem cell injection. A much more favorable study would be to use uniformly graded osteoarthritis graded knees of same age, height and body weight. There are too many variables involved in human medicine that affects outcomes that are not present in animal models, including what humans do when they leave the doctors office that animal models of the goat and sheep do not do.
Animals vs. Humans
Dr. Lox has lectured with many acclaimed professors who do stem cell research. None have yet to state that their animal models run marathons. Dr. Lox has patients who do. Humans don’t always behave the way we want. Interpretation of clinical data needs to include this. Lastly, when the original research was designed knowledge of what happens to stem cells after they divided multiple times to create large numbers of cells was unknown. Now we know that multiple cell divisions actually AGE the stem cells by nearly 30 years. This was known previously with cartilage cell laboratory growth to larger numbers known as autologous chondrocyte implantation (ACI). ACI worked poorly in patients over 50, the chondrocytes were too old when re-implanted. Another important finding has been culturing and growing stem cells to larger numbers alters the stem cell surface membrane where cell-cell signals and cell-cytokine signals are read. This includes the ability of stem cells to home.
Stem Cell Homing
Stem cell homing is what allows the stem cells to migrate to injured or arthritic areas. Stem cells also function as mediators of the inflammatory cascade. This ability to modulate the inflammatory cascade via its secretory or inhibitory of catabolic cytokines is considered a vital component of stem cells medicinal effect.
New Therapies on The Horizon
Many other companies have knee stem cell drugs in clinical trials. The California Institute for Regenerative Medicine (CIRM) has recently given a $33 million grant to develop a knee stem cell drug. There is understanding of how society can benefit from such a therapeutic stem cell drug for knees. Progress is slow, as or current system is hospital based medicine, including surgery. Lastly, fully understanding human as unique individuals must be appreciated in interpreting clinical data.
Exosomes
Many are now switching gears towards microvesicles residing in cells. Exosomes are increasingly being studied. The signals that occur via micro-RNA synthesis may end up playing an important future role in knee pain and arthritis management.
Perinatal Stem Cells
Nothing seems to be more confusing to patients than the vast numbers of groups giving misinformation as the poorly or misstated information given about amniotic, umbilical cord, and placental cord stem cells. It becomes simple when looking at facts. A pure stem cell product derived from another human being to be used by another human being in the United States falls into the drug category. There is currently no pure knee stem cell drug derived from adults or newborns approved as a stem cell drug. What is approved, is tissue products classified as medical devices. These are approved for wound therapy and some are misrepresenting these “medical device” products as stem cells from a younger source “a newborn” therefore better than your own stem cells because “they are younger”. Pure and simple misinformation. Some purposefully misinform others, others do so out of their own lack of understanding, hardly expertise in the Regenerative Medicine or Stem Cell field. To make a pure stem cell product of larger numbers requires cultivation in a laboratory setting, remove all other cellular debris, and expanding the cells to a greater number. This then becomes under the FDA guidelines as a stem cell drug. There are no perinatal new born tissue pure stem cell drugs approved. Pure misinformation. It is up to each and every patient to do their homework and due diligence. If a company is claiming to treat everything from A to Z, this should be a large RED FLAG.
Synopsis of Knee Stem Cells
Companies that tout their ability to grow or culture your cells to greater numbers, and this is in your best interest, should make the keen researcher ask the following questions:
- Have they learned from the Chondrogen design flaws?
- Are they charging the patient more for what Chondrogen learned the hard way?
- Currently the FDA rules are same person same day. This means that your cells and tissue harvested must be used the same day within guidelines of how it may be harvested and prepared. Several companies have set up off shore clinics to do this outside of the US guidelines.
Every patient should do their own research while seeking stem cell treatment.
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