Interesting study in the PLOS Medicine this am on an Israeli boy who has a benign brain tumor from donor derived fetal stem cells. For a less technical version of the story, see yahoo news. I have been asked by many people via e-mail if we would consider treating any number of horrible diseases. Since we have limited ourselves to Ortho, when I say that I can’t, the conversation usually turns to have I heard of this or that offshore outfit and do I think these out of country stem cell treatments are safe? Since the news this morning segways nicely into this topic, here goes.
First, it’s not that surprising that fetal or embryonic cells can cause tumors. They are absolutely not designed to repair things, but instead to build a person. The ISSCR guidelines have done a very nice job of helping to structure a conversation on the safety issues involved in using stem cells as therapy and how to mitigate these risks. However, to simplify:
1. Source of cells matters…
If you had to grade the risks from stem cell therapy from high to low risk, it would be: Donor Fetal or Embryonic Cells>Donor Adult Stem Cells>Your Own Adult Stem Cells. To find out more about this discussion of stem cell types, click here. Embryonic or fetal stem cells don’t have as their primary function, repair. We want stem cells to heal catastrophic disease by repairing diseased tissue. Adult stem cells are primed for repair, it’s what they do everyday you’re alive and kicking. Adult stem cells from somebody else (donor) have some additional risks. We don’t yet know if the host has the epigenetic machinery necessary to control donor cell growth (meaning if you have the ability to control the growth of someone else’s cells in your body). Also, recent research has shown that you not only get the donor cells, but their genes as well, which can add an additional layer of complications. So if you had to bet on one cell type being the safest, it’s your own adult stem cells.
2. Cell Type Matters
If the outfit you’re talking with can’t tell you which exact stem cell type they’re using, hang up the phone. Even if you stick with your own adult stem cells, the type of adult cell matters for the application, both for function and safety. Adult stem cells come in varieties: MSC’s, EPC’s, HSC’s, etc… HSC’s (also known as CD34+ cells) would likely help in cardiac and vascular applications, but not in ortho or neural applications. These cells were born to make new blood products. EPC’s might be good for cardiac applications. The MVP of the adult stem cell world is the MSC (the cell line we use). MSC research has shown evidence of repair of a wide variety of tissues including orthopedic, cardiac, vascular, neural, skin, and internal organs.
There are newer cell types such as VSEL (very small embryonic like). These have great potential, but not much is known or researched on safety. For example, a search of the national library of medicine turn up 15 references for VSEL’s. The same type of search under mesenchymal stem cells (MSC) this moring turns up almost eight thousand articles (7.918). So if we want to know if growing a cell line in culture might lead to cells capable of being cancerous, for VSEL’s we’d be out of luck. For MSC’s, there are multiple articles showing that short term culture has no detecable risk, while long term culture may be an issue (we use only short term culture). How about if we want to know how if the patient’s daily drugs might impact the cells? How about common drugs like NSAID’s and statins? For MSC’s, we can find out in seconds by looking it up in PubMed. For VSEL’s, no such luck. How about a more rare drug like EPO? For MSC’s, two studies, for VSEL’s none.
3. Cell Prep Matters
As discussed above, long term culture of any adult stem cell line will always pose risks. Why? Adult stem cells are repair and maintence cells. As an example, MSC’s in culture will grow quickly under ideal conditions for only a few passages (a week to 10 days), then most lines will peter out. Why? These cells are programmed to grow to the numbers needed for a repair, act as the general contractor to orchestrate the repair, then differentiate into the bricks and mortar. However, any cell line can be tricked into growing for longer than it’s design specs. This is where you can run into problems. So short term culture (like the Regenexx procedure) is better than long term culture.
4. Complications Tracking Matters
Regardless of how safe you make the cell type and prep choices, you still need a mechanism in place to track the outcomes of transplanted cells. This needs to extend for years and involve aggressive attempts to contact all patients treated. In addition, just patient contacts aren’t enough, visual surveillance (like 3.0T or high field MRI) in a certain number of patients is also needed. If the off shore outfit can’t give you details of at least a few years of trailing complications data, hang up the phone. There should also be some scientific publications planned, submitted, or published. If you get your cells and then nobody ever attempts to contact you again, not good. The Regenexx procedure prides itself in it’s complications tracking system that began in late 2005 and is constantly maintained. We also pride ourselves in our 3.0T MRI tracking program. We have submitted a scientific publication on this complications tracking and will continue to do so as the data becomes available.
5. Treating everything
Each stem cell therapy or treatment needs to be individualized for each condition. As an example, we strated trying to treat lumbar discs in late 2005 and just copying the existing animal modeles didn’t work. It took years to refine this treatment to the point where we can now successfully treat a slice of patients with disc bulges pressing on spinal nerves. It takes us months to years to dsevelop each approach to a different orhtopedic issue. The idea that any company could treat all diseases like diabetes, stroke, spinal cord injury, brain injury, degenerative joints, and anything else not tenable. If the compay you’re dealing with tells you they can treat a wide variety of different issues all the same way, hang up the phone.
6. IV Therapy
The research strongly suggests that the best delivery method for stem cells is to place them directly in the site in need of repair. When stem cells are delivered via a simple IV injection, they end up in the lungs. This is called a pulmonary first pass effect. So if you have a lung problem this may be a reasonable way to deliver cells, but delivering them IV does nothing for joints, pancreas, liver, brain, nerves, or spinal cord. So if you’re told that the clinic delivers the cells IV, then hang up the phone.
So in summary, how can you tell the “real deal” from dangerous snake oil? Let’s give an example. There is a reputable company called Regenocyte doing cardiac and vascular work out of the Dominican. They are run by an American cardiologist who places adult stem cells (CD34+ cells) minimally cultured to up regulate VEGF expression in Israel and placed via vascular or cardiac catheter at the specific site in need of repair. This is the “real deal”. Compare that to an outfit that won’t identify what cells they use or are vague on the topic, won’t tell you how the cells are prepared, can’t give you a complications tracking plan, treats everything, and delivers cells IV. Not the real deal.