First, I’m proud to say that our medical practice has cultured stem cells for almost 500 patients and about 1,000 procedures and treated another approximately 1,000 patients with same day processing of their cells without a single lab based infection. Having said that, to avoid those “misadventures” we use processing systems like sterile hoods, random testing of cells in culture, serial microscopic observation of cells, sterile transport of cells, strict SOP’s that define how the sample can be accepted, skilled technicians, and a level of sterility that exceeds the vast majority of in-vitro fertilization labs and operating rooms in the United States. While we’re proud of our practice’s safety record in cell handling, this blog highlights a serious growing patient safety risk that patients need to know about and all professional organizations need to place on the radar.
In the past 6 months there’s been an explosion of clinics offering “stem cell therapies”. We welcome this increased interest and availability of cell based therapies as long as these new clinics use physicians trained to understand the diagnoses and procedures they wield and they operate in a safe manner. Therefore evaluating a stem cell clinic both for safety and for results documented in a registry is essential. The biggest explosion has been in adipose (fat) derived stem cells, mostly used for cosmetic purposes. However, we’ve also noted a precipitous rise in the non-specialist treatment of arthritis with stem cells. Most of these docs are family physicians without specialized musculoskeletal training or cosmetic surgeons injecting joints (a cosmetic surgeon injecting a joint is like one of our doctors injecting cosmetic fillers). In addition, to liberate stem cells from the adipose tissue, many of these clinics use an off the shelf “Shaker Kit” being distributed in the United States as “Research Use Only”, but with the intention of being used clinically in patients. The kit contains a simple emulsifying agent (Lecithin) and a container. The doctor takes a liposuction aspirate, chops it up a bit (usually at the bedside), and then adds this chopped up fat to the container and adds an emulsifier. The mixture is then shaken (not stirred) and then centrifuged. The Lecithin breaks down the structural component of the fat so that the stem cells in the fat (along with many other cell types) are released. The doctor then manually removes the fraction of the centrifuged and enzyme digested fat that presumably is rich in stem cells. These cells are then exposed to a LASER to “activate” them and then finally injected. I say presumably containing stem cells, because there is no lab used to confirm what’s actually being isolated, if the stem cells are dead or alive, or if there are any stem cells at all. Since how the cells are processed will impact if viable stem cells are obtained, simply giving the doctor a training course on how to perform liposuction and use the kit won’t suffice. There has to be some validation that the doctor or medical assistant using the kit is actually able to obtain stem cells out of the process-which should be checked by a lab until the doctor demonstrates competency. There also has to be training about how and when these cells might be useful to the patient, which clinical diagnoses are more likely to be helped, and how to deploy the cells. These later details are often left out by the kit vendors. Finally, any physician using an “investigational” procedure has an ethical obligation to enter his or her patients into a registry that can track the patients for outcomes and complications. Simply applying usual in clinic follow-up care or having a nurse call the patient after the procedure is not nearly enough, as by definition, an investigational procedure still has unknowns. None of these last steps are often followed by the doctors using these “Shaker Kits” or many other doctors processing fat in their offices.
There are also safety issues with a doctor or assistant using this kit to process cells at the bedside. When one very smart colleague observed the kit in use, she noted that all of this was literally being performed in a dirty store room of a clinic where a non-sterile surgical drape had been placed on a card table. While the system had been advertised as a closed system (meaning that it was less likely to become contaminated) it wasn’t. There were multiple times that the tissue, exposed to the dirty air in the backroom and other dirty surfaces, could have become contaminated. Much to my colleagues surprise, that particular sample, after this less than aseptic processing, went back into a patient.
Good medicine is good medicine. There are two extremes for cell processing and like anything in life, moderation is the best choice. On the one extreme, some believe that any cell processing should occur in a multimillion dollar drug manufacturing facility with millions a year in compliance costs. This makes little sense and will only serve to increase the cost of cell based therapies much more than reduce patient risk. As an example, surgical tissue is often handled in the Operating Room in a sterile manner by properly trained surgical staff with very low infection and cross contamination rates. In addition, cell culture for the 5 and 7 day blastocyst transfer procedure (one of the many in-vitro fertilization procedures couples use to conceive) has been performed for decades with operating room levels of sterility-with almost zero infection rates. So while drug factory processing doesn’t make sense, cells taken out of the body and processed by a medical practice during the same surgical procedure, whether outside the body for minutes or days, need special handling. For this type of processing, the sample should be collected in a sterile manner, transported some short distance over a short time (or validated in a longer transport so that the cells can be kept healthy and free of infection) and processed in a sterile hood by a technician observing good medical practices and sterile technique. If the cells are cultured this process should be performed with many more reasonable safeguards to reduce patient risk. Whether the tissue is delivered back to the physician the same day or cultured for some time, the processed tissue should be transported in the same safe manner to be re-injected. The International Cellular Medicine Society has promugated best practices guidelines for how this should occur. However, many of these key patient safety steps are skipped by physicians using the Shaker Kits I’ve described. In addition, many of these important safety steps are missed by many of the clinics processing fat in this country and overseas.
Take for example this story from courthouse news (my summary of the allegations leveled by the plaintiffs in the malpractice case):
-A patient wanted his knee arthritis, elbow, and low back pain treated
-The patient didn’t consult a medical specialist knowledgeable about knees, elbows, and backs, but instead a PhD who is a psychologist and hypo-therapist
-The patient went to see a cosmetic surgeon to have his fat stem cells harvested using liposuction (without confirming that the plastic surgeon had any idea of how to collect cells without traumatizing or killing the cells, not an easy task)
-Based simply on the details in this story, the cosmetic surgeon had limited knowledge of how this sensitive biologic tissue was to be transported, so he released it to the patient, who placed it in his refrigerator overnight
-The cells eventually made it to a lab in California that took several days processing the tissue (if the goal was to obtain stromal vascular fraction or SVF-the fact that the cell processing, which can be performed in about an hour by an experienced technician, took days is yet another red flag).
-The cells were then taken from California to a Mexican clinic in a grocery bag, where the Mexican doctors had the good sense to question the appearance of the cells and the manner which they were transported-but still injected them anyway
-The cells were then injected into the patient’s knee and elbow (unknown if imaging gidance was used to confirm that the cells were really making it into these joints-but unlikely) and eventually into the muscles of the low back
-While there is reasonable justification for placing fat derived stem cells into joints to help cartilage repair, there would be no rationale for why adipose stem cells injected blindly into low back muscles would help this patient’s chronic low back pain
-There seemed to be no diagnosis by any doctor of what was specifically causing this patient’s knee, elbow, and low back pain-which would have dictated exactly where to place which type of stem cells and why
-Within days of the injections, the patient developed a very serious and rare infection from contaminated cells, which more than a year later is still being treated
The patient is now suing the doctors for malpractice. Whatever the truth (or lack thereof) behind the allegations, this is the appropriate place for this type of cell therapy to be regulated (local medical boards and the courts). Just as a surgeon who handles tissue improperly without sterile technique and/or does a poor job performing the surgery, the doctor responsible is liable to his own medical board and can be sued in court for any misadventures. What’s frightening about this example is that we know of several companies performing this type of transport with cells and many more doctors using these shaker kits without processing under a sterile hood. Again, multimillion dollar drug factories are not required for autologous cell processing and in-vitro fertilization lab culture has been performed safely for decades with operating room type sterility. However, the type of operation described in this story and the ones springing up across the US as I write this post where physicians process stem cells outside of basic patient safety requirements like sterile hoods, makes me think we’ll see many more of these adipose stem cell “misadventures” in the days to come. In particular, since many of these physicians inject these cells intravenously, oblivious to issues like cell clumping that can lead to serious or fatal blood clots or contaminated cells that can cause serious body wide infection, regrettably the next complications we may hear about are the worse type possible – deaths.