CHAPTER 1
THE SCIENCE OF STEM CELLS
Stem cell: an unspecialized cell that can differentiate (i.e. change into) a specific specialized cell; also has the capability to replicate.
The mention of stem cells raises tremendous controversy, such that the American public tends to presume two things: 1) That the cells in question are embryonic cells, harvested from the tissue of aborted fetuses, or dead fetuses created and altered in a laboratory for scientific purposes, and 2) That actual operations using stem cells derived from human tissue will be a phenomenon of the distant future – they won't be available here in the United States for at least another decade. Yet here at the California Stem Cell Treatment Center, our patients have been receiving "stem-cell" injections since December of 2010. If conventional thinking places stem cells squarely in the future, how is it possible for us to offer leading-edge treatment right now? And is this even legal?
For starters, the cells that our team works with are non-embryonic cells; CSCTC uses strictly adult (not fetal) tissue and autologous cells, meaning the cells are taken from the person that receives them – donor and recipient are one and the same. Embryonic cells are hailed in the media for their pluripotent property, meaning they can differentiate into any type of cell in the body. However, embryonic cells don't relate well to adult tissue; they want to grow into a fetus, which is abnormally rapid growth in any context other than a pregnancy, resulting in the formation of teratomas which is a type of uncontrolled neoplastic (cancerous) growth. Such tumor formation has been clinically documented and has severely limited the clinical use of embryonic stem cells which is problematic since most of the basic science stem cell work done in the past 15 years has been using these embryonic cells. The adult cells that we use at CSCTC are not pluripotent, but they are plenty potent for regenerative healing. These adult stem cells (ASCs) derived from fat have been documented to be capable of forming nearly every type of tissue in the human body except placental tissue. We have proof that fat derived stem cells can form nerve tissue and other complex organs. (See addendum- History of Adipose Derived SVF).
Learn to love your body fat: It's loaded with mesenchymal stem cells, a.k.a. multipotent stromal cells, or MSCs, that can differentiate into a variety of cell types. These same cells may also be isolated from several other sources in the body, including bone marrow and the umbilical cord (cord blood cells are adult cells, not embryonic ones). For millennia, the lifeline joining mother and infant was discarded after birth; in recent years, however, growing scientific awareness that the umbilical cord is a rich reserve of stem cells has spurred the development of technology enabling parents to choose the option of having their cord blood preserved and cryobanked (deep frozen at -190°C) for their own and their children's future medical use. However, the focus on the cryopreservation of cells has been to bank HSC's also known as hematopoetic stem cells, which are a type of stem cell that is especially intended to form blood products and can be useful in patients that have blood line tumors like leukemia and need therapies that destroy the persons own blood and immune cells which then need to be repopulated with HSC's. There are a very small number of MSC's in umbilical cord but this is a poor source compared to fat.
Bone marrow MSCs have been used for a number of years, particularly for a variety of orthopedic conditions; however, they are found in relatively low numbers, and require FDA approved laboratory growth (using GMP also known as "good manufacturing practices") to ensure adequate amounts for regenerative purposes. Also, with chronic illness and advanced age the bone marrow is suppressed, and this negatively impacts the quality and quantity of the cells. As cancer patients who have undergone harvesting of their bone marrow appreciate, the removal process is difficult, painful, and invasive. As noted above, the MSCs used at our practice are adipose-derived cells, meaning they are harvested from the patient's own fatty tissue. It turns out that fat has 2,500 times the number of MSCs as bone marrow; the cells simply lie dormant in the collagen matrix of the fat, but can be made readily available for release and bio-available to our damaged tissue for repair purposes. Scientists abbreviate the term adipose-derived stem cells as ASC, to distinguish them from bone-marrow-derived stem cells, or BSC. While different camps will try to argue that bone marrow cells have advantages over fat-derived cells, studies show that the cells derived from fat are equal – if not superior – in regenerative potency to the stem cells derived from bone marrow.
At CSCTC we employ a "mini-liposuction" technique to remove the fatty tissue. Liposuction has been the single most popular cosmetic procedure in the United States for several years now. Of course, with basic liposuction the goal is to remove unwanted fat that the patient can't otherwise lose by normal diet and exercise. Amazingly, while fat frequently finds use in transplantation for facial rejuvenation, breast augmentation, buttock augmentation, and a variety of "defect" repairs, it is otherwise largely discarded. Today, we know that there are 500,000 to 1 million stem cells in each milliliter of fat – yet during routine cosmetic procedures, surgeons were discarding what amounted to billions of these incredibly important regenerative cells. In most cases, the MSC-rich adipose tissue continues to be discarded. Most liposuction procedures require some type of sedation in addition to local anesthesia; however, at CSCTC we've developed a very rapid and simple technique for harvesting fat using only local anesthesia. It's over in about 15 minutes. Even doctors that perform liposuction that have had the procedure done on themselves find it surprisingly pain-free and simple. "It's like going to the dentist," they say (plus, it's usually a lot less painful).
The cosmetic surgeon and the urologist may seem like the premise for a "two doctors walk into a bar" joke. But believe it or not, it took exactly this medical odd couple to start a stem cell practice despite the mainstream media and medical community's insistence that stem cells are the stuff of theory, not practice – and to make this therapy available today to people who need it.
As a top cosmetic surgeon in Beverly Hills renowned for face lifts, Mark kept current with scientific studies of adipose tissue all over the world, fascinated by what was becoming increasingly evident: that "the magic of fat" went far beyond the cosmetic surgeon's gift for rejuvenating aging faces. ASC's healing potential may be easily, safely, and efficiently harvested and repurposed for therapeutic purposes including arthritis and orthopedic injury. Mark felt a professional duty to deploy SVF to help patients with more than just aesthetic medical issues. But, as a cosmetic surgeon, he would've been beyond his scope of practice if he were to start treating joint conditions. So he convinced a leading Westside orthopedic surgeon, Dr. Thomas Grogan, to consider treating patients with him. After discussing the possibilities, Grogan agreed to evaluate patients sent by Mark. Pretty soon, patients were asking Mark to address their issues with aging joints instead of aging faces.
Our original concepts were developed based on a casual conversation ... "I remember when Mark returned from Japan and was sitting with me talking about how using stem cells for cosmetics was actually a waste of valuable cells when one considers the tremendous therapeutic potential of these cells. It was one of those epiphany moments and I told Mark he was right and not only was he right, but that we were going to do just that. But we both understood that we had to do it correctly. We did not want to get painted with the same broad strokes as those clinics that offered cell therapy but without rigorous protocols, data collection, and standardization of procedures. Mark and I decided to study the investigational use of stem cells found in stromal vascular fraction and offer it to our patients ethically and safely. We understood that we had to charge our patients but we set fair rates and called it patient funded research. After all, who else would fund such a project? Government and private industry had no industry in funding the study of a person's fat derived stem cells- a personal biologic that was not patentable or capable of being manufactured for commercial purposes."
Elliot as a urologist, quickly began thinking about treating so many urologic degenerative disease, such as erectile dysfunction which afflicts some 65 million Americans. The possibilities were unlimited: if this could be done as a surgical procedure rather than a laboratory based product application, then cell therapy could be made readily available to patients everywhere in the world today without an expensive laboratory or inaccessible university research program.
A cosmetic surgeon ... a urologist ... well, who else is going to undertake this work? There is no special residency or training for stem cell therapy. But if you're a surgeon, and someone arrives from Japan to hand you a new recipe with tremendous healing potential, aren't you obligated to do something with it, to help people? We think so. We're all physicians before we differentiate into specialists. Eager to help patients struggling with medical issues that were more than just cosmetic, and anticipating demand for this exciting new therapy, Mark crossed over into therapeutic practice – a rare move for a cosmetic surgeon. Meanwhile Elliot, the urology specialist, undertook something equally out of the ordinary: mastering the cosmetic surgeon's liposuction procedure, so he too would be ready to extract and deploy ASC.
The procedure is simple enough that any physician with an MD degree, regardless of his or her chosen specialty, can easily perform it after undergoing a training session. Here's how it works: Patients undergo a mini-liposuction that yields the stromal vascular fraction (SVF), a protein-rich segment from processed adipose tissue. SVF contains a mononuclear cell line comprised mainly of autologous mesenchymal stem cells (fat derived and peri-vascular blood vessel derived stem cells), macrophage cells, endothelial cells, red blood cells, immune cells, and growth factors that facilitate the stem cell process and promote their activity. The fat sample is processed in a centrifuge in our treatment room as part of the surgical procedure; our technology enables us to isolate large numbers of viable cells, for optimal regenerative effect. The patient's SVF is then injected back into their body, either directly into the inflamed area (such as the knee or hip joint) or into the bloodstream, via an intravenous injection. When delivered by IV, the cells travel through the vascular system in search of areas of inflammation; the cells target those areas and then the damaged tissue activates the stem cells to begin the regeneration process.
Confident that we both had sufficient experience with this new method, Elliot came up with the idea to join our two practices – Mark's Beverly Hills office and Elliot's office in Rancho Mirage – and reincorporate both as branches of the California Stem Cell Treatment Center- dedicated to the investigational study of SVF. We set up our educational website www.Stemcellrevolution.com and in December of 2010, we treated our first patient at CSCTC. The first person to be treated with his own stem cells at the newly renamed facility was a Canadian businessman who'd endured neck and shoulder pain for many years; he had full resolution of his symptoms, and his success is durable to the present time. Like many of our patients, he later offered to invest in our clinic but we continue to remain privately owned in alignment with our philosophy to be physician owned and controlled. Because the service we offer is a totally closed procedure (the entire process is performed without exposure to the environment) – basically a therapeutic variation of Mark's perfected technique of extracting fat for cosmetic purposes – it is absolutely legal to perform since it is a type of lipo-transfer surgery. If it would be a laboratory procedure, it would not be FDA compliant, but it's not a laboratory procedure. We modified the technology to make it a surgical procedure instead of a laboratory procedure; we're one of only groups in the world doing it this way.
Other American facilities working with stem cells are laboratories, and all labs must be overseen by the FDA, to prevent disease transmission. This explains why the science pundits predict that stem cell practice won't be available for years to come. But because we perform closed surgical procedures on individual patients, we don't have to worry about communicable disease. What we're doing is not FDA-approved, yet it's FDA-compliant, completely legal, and available right now. We proudly follow the FDA's guidelines, but what we're doing is not under the FDA's jurisdiction because it's a closed surgical procedure. The FDA regulates drugs and medical devices but it is the respective State Medical Boards that regulate the "practice of medicine." As such, our protocol is no different than Mark extracting fat from his aesthetic patients and re-injecting it into their faces – and he's been doing that for almost 30 years. As we've proved with our own on-the-job training, any doctor is able to pick up the technique, no matter how general or specialized the practice s/he operates.
CSCTC is the first American medical practice to offer treatment with adipose derived stem cells in a methodical, investigative, academic, and organized manner. As the first to do this the way we do, initially we faced a great deal of criticism. We had to fly in the face of some peer issues, as competing clinics were located offshore and their quality was perceived as dodgy. Plus, we didn't have any funding, so we invested thousands of dollars of our own money and substantial time diverted from our own lucrative practices because we believed in what we were doing. Colleagues advised us to wait for peer-reviewed studies, otherwise we're "charlatans" and our treatment is so much "snake oil." But we saw no reason to delay putting this proven technology to work, to help people who need it and to educate as many other doctors as possible. We've been doing this for four years now, in a meaningful, controlled way, and we've treated more than 2,000 patients. If we evaluate a patient only to conclude that SVF wouldn't help the person, we won't treat that patient. We turn away as many as 20 percent of people who apply to us for treatment.
What CSCTC definitely does not do is culture cells to increase their strength in numbers. We cannot by law. Although cell culturing is currently par for the course in Spain, Russia, Sweden, Asia, and offshore, here in the United States, if you grow (i.e. manipulate) cells, then by definition you become a drug manufacturer – and at that point you're under the auspices of the FDA. Culturing cells is beyond the scope of minimal manipulation, so growing is, for now, verboten. Hopefully, that restriction will soon change, as the ability to culture cells will permit American doctors to perform life-saving procedures such as generating custom, rejection-proof donor organs seeded with the transplant recipient's own cells (as Dr. Paolo Macchiarini did when he achieved the world's first tissue-engineered trachea transplant in Barcelona in 2008). Once an organization demonstrates FDA approved Good Manufacturing Practices (GMP) to culture (i.e. replicate and increase the numbers of cells), thus avoiding risk of disease transmission, then your own cells will eventually be available in even greater numbers. You will eventually bank your cells and get huge returns with interest. This brings possibilities are nearly unlimited such as creating your own individual lines of stem cells that could later be used not only for repair work but also to fight cancers since our stem cells have the ability to bring cancer therapies directly to damaged tissue where malignancies are growing. Many labs around the world are now looking at exploiting the cancer homing and identifying properties of stem cells and this area of stem cell science is attracting a lot of attention and interest today.
OK, we had "lightning in a bottle." We could have kept our technology proprietary by operating a niche clinic to help our patients exclusively, but our vision was to make regenerative therapies readily available to people who need them most, while rapidly increasing our ability to perform studies for safety and efficacy. Our hope was that someday, perhaps we could modify the way health care would be delivered in this country. In 2012, we made the decision to reach out to research partners and collaborate to spread the technology in a controlled fashion by starting the Cell Surgical Network to train research partners to collaborate on protocols and collect data together. If we selected key physicians who could participate in our investigative studies, and we conveyed our intellectual property freely to those physicians, then we could help even more people, and more rapidly advance the field.
