The confusion over fat vs bone marrow stem cells has always been fascinating to watch. At the end of the day, being the first physician in the US to use stem cells to treat orthopedic problems in patients, I’ve seen it all. This week a physician was discussing with his colleague the merits of their practice either adopting stem cells from one of these sources and I thought this would be a great way to educate patients and physicians about some of the things we know about this comparison.
There’s little doubt that bone marrow vs. fat stem cells is a bit like the Coke versus Pepsi of our time. Feelings run deep on both sides and when that happens, sometimes reality gets tossed out the window. For the most part, physicians have little verifiable fact, and an awful lot of either marketing speak or misinformation that some guy told some guy who told them.
To better put a little reality in the discussion, I’ll begin with one doctor’s statements in an e-mail to another doctor. The second physician contacted us because he liked what we did at Regenexx (Coke), while his colleague liked fat stem cells and a national network of clinics who use that technology (Pepsi). Here are excerpts from the e-mails:
“1. SVF is at least equivalent if not better than bone-marrow concentrate (BMC) techniques (that do NOT involve cell culture and expansion) in terms of mesenchymal stem cell counts, number of adherent cells, pericytes, and colony forming units. There’s also at least in vitro evidence that SVF more effectively differentiates into cartilage than BMC, and SVF typically contains fewer leucocytes than BMC, which some authors believe may impede healing.”
Let’s break these down erroneous statement by even more erroneous statement:
“SVF is at least equivalent if not better than bone-marrow concentrate (BMC) techniques (that do NOT involve cell culture and expansion) in terms of mesenchymal stem cell counts, number of adherent cells, pericytes, and colony forming units.” As I’ve discussed before, this concept that SVF has more stem cells is based on a 5th grade math division error. This is a great video that discusses the fat stem cell vs. bone marrow count problem. So in reality we have no data that shows that fat has any more stem cells than bone marrow, in fact it lacks or is poor in important cells for orthopedic purposes that bone marrow has in spades (see video).
“There’s also at least in vitro evidence that SVF more effectively differentiates into cartilage than BMC…” This statement isn’t supported by the literature at all, in fact it’s 180 degrees from what’s published. This is a link to an infographic that looks at 13 consecutive studies that show that MSCs from bone marrow have greater ability to differentiate into cartilage than those from fat. Why is this the case? The ability of any resident stem cell to differentiate into any tissue is generally governed by the functions that those cells perform in the body. Bone marrow interacts with the joint space all the time, as it lives just below the cartilage surface in every joint. Subcutaneous fat from your belly or thighs or butt has nothing to do with any joint function.
“…and SVF typically contains fewer leucocytes than BMC, which some authors believe may impede healing.” This statement is like a 30,000 foot view of a football stadium out of a plane window where the guy in the window seat claims to be able to make out the numbers on the jerseys of the players. For it to have any meaning, we need to first bring it down to earth a bit.
Both fat and bone marrow contain leukocytes, or white blood cells. These are the cells that respond to disease and make up a part of the immune system and they include lymphocytes, granulocytes, monocytes, and macrophages. There’s an unsettled debate in platelet rich plasma (PRP) research over whether having these cells in the mix is a good or bad idea-there is no such debate in the stem cell community on this issue as both same day bone marrow and fat stem cell procedures have them in spades. Of these cells, one stands out as being a big player in regenerative medicine-macrophages.
Macrophages are physically huge cells that dwarf other cells and can act like a janitor who cleans up messes. Their job is not only to gobble up debris from injuries, but they can also have a Dr. Jekyll and Mr. Hyde personality in that they can also gobble up good cartilage in arthritic joints. These two forms of a macrophage-activated and non-activated are key to understanding their utility in tissue repair.
Activated macrophages (Dr. Hyde cells) are critical for fighting invading bacteria and as such they’re switched on by inflammatory cytokines that are present in acute infections. However, American couch potatoes with big waistlines have a little problem, inflammatory cytokines course through their bodies in a big way leading to diabetes, heart disease, and stroke. These same chemicals also activate their macrophages, turning the mild mannered inactivated Dr. Jekyll cells into Mr. Hyde beast mode cells that attack cartilage.
While bone marrow has a reasonable number of macrophages, obese patients have a hugely amplified number. For example, in lean animal models, only about 5% of the cells are macrophages, but in the severely obese this climbs to as high as 50%! This macrophage accumulation in fat is considered a key problem of obesity and a big player in the bad health effects of metabolic syndrome. Hence while lean patients may have few activated Dr. Hyde type macrophages, the patients most likely to have arthritis (those who are overweight), have huge reservoirs of these cells in their fat that will end up in the stem cell treatment once that fat is harvested. In addition, obese patients also have less potent mesenchymal stem cells in their fat than lean patients and these stem cells cells are less healthy.
“The only Regenexx procedure that actually isolates and cultures cells, thus greatly increasing cell counts and the likelihood for good results is the Regenexx “C” procedure, where harvested bone marrow is sent to the Regenexx lab for processing…the Regenexx “C” procedure is as of 2010 available only in the Cayman Islands. All of the other Regenexx stem cell procedures which are performed as “same day” or “SD”, use a simple mixture of bone-marrow aspirate and what amounts to essentially platelet rich plasma. Obviously, this does nothing to improve the harvested cell counts, which in most cases are at least 10 to 20 fold lower than cell counts for adipose harvest, even taking into consideration the potential errors inherent in methods used for performing these counts.”
This statement falls into the same 5th grade math division error as the one above, throwing out random numbers about how many more stem cells that fat has than bone marrow. Again, these numbers aren’t remotely accurate as the video above shows. Hence, there are not fewer stem cells in our same day bone marrow stem cell procedure than in a same day adipose stem cell procedure, only a heck of a lot more stem cells in the cultured procedure we license down in Grand Cayman.
The remainder of the e-mail exchange covers a gimmick that some adipose SVF physician networks use to try to avoid regulatory action. Basically, the e-mail acknowledges that adipose stem cells prepared in a doctor’s office are considered an unapproved drug by the FDA. However, the doctor who liked fat stem cells claims that he’s been told that if the marketing for the physician network focuses on an “IRB Approved Study” that this makes everything OK. Nothing could be farther from the truth, as this approach only compounds the doctor’s problems, let me explain.
IRB stands for institutional review board or a group of doctors and other community members who review and approve research to maximize patient protection. What most practicing physicians don’t realize is that there are two types of IRBs-a simple community model and usually an academic IRB that has a Federal Wide Assurance (FWA). Since adipose stem cells are a drug, the approval needed would be from an IRB that has an FWA to supervise drug approval studies. The IRB that this physician network used doesn’t have an FWA, so when the FDA decides to show up, not only is the doctor liable for not having FDA approval for the fat stem cell product which will be misbranded and adulterated, but also for the fact that there is no IRB approval from a review board licensed by the FDA to supervise drug studies. So the marketing gimmick of trying to look like the network is only performing research actually gets the doctor who is illegally manufacturing fat stem cells in his back office in more trouble, not less. Does the same thing apply to the same day bone marrow stem cells we use-no, as the end product of the processing isn’t considered a drug.
The upshot? I debated how best to rebut this e-mail, as we have two doctors who clearly are advocates for different technologies, which in and of itself is great. Having said that, when the marketing speak of one side gets disconnected from reality, it should be brought back to ground so that every doctor can learn.