Dr. Bunyak was asked by the San Diego Union-Tribune to comment on today’s news story regarding a recent study of clinics across the country offering “unapproved” stem cell therapies.
The Trib article can be found online here:
After reading the article in full, Dr. Bunyak would like to add the following:
“There has been a lot of media attention on stem cell therapies and stem cell therapy providers in the recent months. Positive studies showing adult stem cell therapy efficacy in certain disorders like osteoarthritis, heart failure, peripheral vascular disease, and stroke, to name a few, are printed side by side with alarmist reports warning consumers away from “cowboy” stem cell clinics and smear campaigns by one group of stem cell clinicians and/or researchers against another. The truth is difficult to separate from fiction.
Here’s my analysis:
There are two main autologous sources (from and returned to the same patient) of stem cells currently used in musculoskeletal clinical practice: bone marrow concentrate and fat cell portion called stromal vascular fraction (SVF).
The bone marrow concentrate is usually an in-office procedure where a sample of bone marrow is aspirated from the posterior iliac crest, concentrated in a centrifuge or commercially available system, and re-injected into an arthritic joint or area of injury. The downsides of this source of stem cells are the relatively low numbers of mesenchymal stem cells per ounces of bone marrow, the decrease in the numbers and quality of these stem cells with time, and the minor risk and pain related to the procedure. The benefits include the possible advantage the bone marrow mesenchymal stem cells have over their fat-derived counterparts in their ease/speed of differentiation into orthopedic tissues such as bone, the possible role of hematopoietic stem cells in augmenting the regenerative process, the relatively longer history in medicine of using bone marrow as a stem cells source, and the perception that bone marrow is somehow a more homologous source of stem cells than fat in joint arthritis applications.
The stromal vascular fraction is obtained, also, in an office-based mini-liposuction/aspiration procedure. The fat sample is then washed with saline, releasing the stem cells, which are found around the capillaries, into the aqueous solution. The fat is the discarded and cells are concentrated and collected after a brief centrifugation, before being injected into the arthritic joint or soft tissue defect. While enzymes such as Collagenase can be used to release greater numbers of cells, recent research demonstrates that enzymatic digestion is unnecessary, and that minimal processing such as that described above yields millions of mesenchymal stem cells safely, easily, and in an FDA-compliant way. The benefits of using fat as a source of stem cells are: 1) numbers–fat has many more mesenchymal stem cells per once than does bone marrow; 2) The mini-liposuction technique is extremely low risk and is relatively comfortable; 3) The clinical studies that use fat as a stem cell source show greater percentages of arthritis patients having higher levels of improvement than do the studies using bone marrow; 4) Fat retains higher levels of stem cells later in life, making it an attractive stem cell source for patients over 65. The downsides are the strengths of bone marrow–namely, the lack of hematopoietic cells and the slightly lower differentiation potential.
As stem cell knowledge evolves, it is becoming clear that each stem cell source has some unique features/advantages/disadvantages and that each patient may benefit from a personalized treatment plan including, when appropriate, fat, bone marrow, or a combination of stem cell sources for optimum results.
The evidence in adult stem cell use is growing. There is emerging evidence, including several large-scale studies, demonstrating both safety and efficacy of stem cell therapies in orthopedic conditions:
Michalek, et. al., published a multi-center study involving 1,114 patients with knee or hip arthritis, grade 1 (mild) to grade 4 (severe), who received SVF (fat-derived cellular therapy, most cases processed without enzymes in a minimally manipulated fashion) and followed up to 54 months. 91% of patients sustained at least a 50% improvement as measured at the 12-month mark without any serious complications.
Centeno has published numerous case series demonstrating the safety and efficacy of bone marrow stem cells in arthritis.
Several recent intradiscal injection studies looking at injections of PRP, SVF, or bone marrow concentrate for discogenic pain related to degenerative disc disease show response rates of 60-90%, rivaling that of fusion or disc replacement surgery.
These studies add to the knowledge on the safety and efficacy of cellular therapies gleaned from over a decade of animal SVF research and practice as well as human bone marrow experience.
The FDA has guidelines in place that differentiate medical procedures using a patient’s own tissue (which are governed by the medical boards rather than the FDA as part of the practice of medicine) from drugs, devices, and foods under FDA oversight. To qualify as a medical procedure and not a drug, thus maintaining FDA compliance, the procedure needs to satisfy the following criteria: it needs to be autologous (or belonging to the same patient); it needs to be minimally manipulated (so it can be washed, shaped, and cells can be selected and collected, but it cannot be grown in a lab and the cells cannot be altered in any way); it needs to be homologous (or placed in a body part where such tissue is or can be present naturally and performs the same or similar function as in the donor tissue); and the procedure needs to be completed during the same visit (rather than on two or more occasions). Both bone marrow and fat-derived stem cell procedures fit the above criteria:
1) Both are autologous–both are collected from the same patient.
2) Both are minimally processed–as described above, each procedure entails nothing more than collecting the tissue (bone marrow or fat), washing the tissue (fat), and selecting the cells we need by centrifugation (bone marrow or fat).
3) Both involve collecting the tissue, selecting the cells, and re-injecting them during the same procedure and on the same day.
4) Both involve homologous use of tissue when injected in a joint, tendon, or ligament. Bone marrow is present inside the bones and is found inside the joint in cases of fracture and during surgical procedures such as microfracture. Fat, too, is normally found in and around the joint. In the knee, Hoffa’s fat pad is intracapsular, attaches to the anterior horns of the menisci, inserts on the intercondylar notch in 50% of patients, and can be injured during ACL tears. The pericruciate fat pad is located in the intercondylar fossa, intimate with the cruciate ligaments. Additionally, when a popliteal cyst ruptures or there is a capsular tear, the joint fluid comes in contact with the fat deposits in the soft tissues around the joint, bringing SVF cells into the aqueous joint fluid. Both sources contain mesenchymal-type stem cells that can differentiate into cartilage cells, tendon/ligament cells, fat cells, and bone cells, thus performing the same function as the native mesenchymal stem cell population found in and around the joint and replacing the mesenchymal stem cells and cartilage cells lost in arthritis.
This fall, the FDA will be holding hearings with researchers, clinicians, industry leaders, patients, and lawmakers to further clarify its stance on stem cell procedures. I, alongside most reputable physicians and researchers involved in stem cell therapies, have been watching the evolving debate closely. Many of us are working with the FDA in shaping this policy. At this time, both procedures are clearly within the current definition of minimally processed tissue and thus compliant with the current FDA regulations. If these change, we will follow the new regulations while continuing to strive to offer our patients the best treatments supported by the latest research.
I would like to end in saying that I, as a physician, feel a responsibility to each of my patients to keep them informed of all of the options available to them, to educate them on the risks, benefits, alternatives, and current state of research of each option, and to help them decide on their individualized treatment plan. Given the recent explosion in regenerative research, controversy, and marketplace, stem cell therapy is necessarily part of these discussions. I would not be doing my job if I did not include a discussion of both fat and bone marrow-derived stem cells, as much to answer questions and share data, as to correct misinformation disseminated by less scrupulous stem cell clinics and the media. Recent articles and blog sites obscure the issue in inflammatory language, and while trying to protect patients from questionable providers, limit patient access to, and understanding of, recent scientific advances in regenerative medicine and how these can translate to expanded choices and better outcomes today.”