Reading the recent media on Stem cells, it’s easy to see why many patients would consider stem cell therapy the modern equivalent of the “fountain of youth”. As a result, many patients believe magical things can happen if their stem cells are used for treatment. The ISSCR has criticized many international stem cell clinics for only touting their case reports of successes without also discussing their treatment failures. I have blogged on the fact that we don’t have a 100% success rate and that we spend a lot of time trying to see if patients are a good fit for our type of stem cell therapy. Our prospective grading system (where we review films to determine if the patient is or isn’t a GOOD, FAIR, or POOR candidate) shows that we tell about twice as many people that they are FAIR candidates and twice as many that they are POOR candidates for every one person we classify as a GOOD candidate. This means that few patients are told they are GOOD candidates. While we’re very proud of some of the amazing things we’ve been able to do to help patients avoid the need for surgery, even in patients who we classify as “GOOD’ candidates, sometimes the procedure doesn’t work. Why?
There are many factors in the research and in our experience that explain why a stem cell procedure may not work in any given patient. The surgeons have known for years that what works well in one patient may fail in another. In stem cells, we believe the following variables are important:
1. Age. There are conflicting studies on how age impacts adult stem cells. Some show profound declines in stem cell function in older animals while other show the same function, but fewer adult stem cells. The truth may be somewhere in between. Older patients likely do have fewer adult stem cells and the very old may have less stem cell function.
2. The local micro-environment. What does that mean? Picture growing a plant in your garden. You take for granted that the soil conditions, water availability, and sun exposure can impact if a plant grows well in a certain spot or poorly in that area. These conditions are the local micro-environment for the plant. The same holds true for stem cells. The place where they get re-implanted may or may not be suitable to support their growth and engraftment. This can be as simple as poor blood supply in an area or as complex as the area being too acidic or having too much bio mechanical pressure to support growth. It may take decades to figure out all of these variables.
3. Medications. We have seen that certain prescription medications make stem cell expansion more difficult. This also isn’t the same for everyone. For example, while some patients on certain blood pressure medications may be able to grow cells well, others may have difficulty. Some of these may be differences in the way the genetics of certain patients react with certain drugs. After all, practicing physicians have known for years that drugs well tolerated by most patients often cause significant side effects in others. It may take decades before we fully understand all of these genetic interactions with medications. In the meantime, we often council our patients to get off as many prescription meds as possible before their cells are harvested.
4. Physical activity. We generally find that patients who are at the highest levels of physical activity (5-10 hours a week of high level physical activity) produce better cells than the average American couch potato. This makes some sense, as these patients with extremely high activity levels generally have more natural growth hormones circulating in their bodies and have fewer physical conditions such as insulin resistance which may impact stem cell function.
5. Health status. We see clear trends that patients in poor physical condition with co-morbid diseases such as heart disease, diabetes, hypertension, etc… generally produce poorer stem cell yields than their healthy counter parts.
6. Severity of disease. We do see trends that more severe disease is harder to treat than less severe, but are constantly surprised that some patients we expected to do poorly do well and vice-versa. It may be that some of the factors above come into play. I can recall a case of an 88 year old man with hip osteoarthritis that we classified as a poor candidate because of his age. He wanted to try anyway. He did extremely well. However, at 88 he was a “specimen”, still able to hike in the mountains for 3 hours a day despite his pain and ski racing until age 85.
7. Unknowns. All of the factors that impact stem cell function may not be fully deciphered in our lifetimes. This is because there is a complex interplay of factors including genetics, epi-genetics, chemical, environmental, that can impact cells in chaotic ways.
The best any physician practicing regenerative medicine will be able to manage for the next few decades is controlling some of these variables. We constantly look at who’s doing well and who’s not, but even large studies can only say who might be more likely to respond, not who exactly will respond. Such is the “art” of medicine.