Adipose Derived Stem Cell
*** NOTICE- Adipose Derived Stem Cell therapy is no longer offered at Advanced Orthopedic Specialists. There are two major reasons for withdrawing this therapy. The first reason is the fact that we discovered a "flattening effect" of this therapy option in many patients. We keep very close track of all our patients with standard outcome tools such as the visual pain analog score and the Western Ontario McMaster's University Arthritis Osteoarthritis Index (WOMAC). Over the past four years and evaluating over 400 treatments, we discovered that the benefits of this therapy were good, but only for periods shorter than we were seeing with Bone Marrow Concentrate therapy. Although, you may read studies or opinions where more stem cells are found within adipose tissue, these cells are not the only cells important in the relief of pain and restoration of function. Bone marrow therapies provide a complete package of regenerative therapies including reducing the levels of IL-1b as well as adding in platelet derived growth factors and reducing harmful chemicals found throughout your joint . Only bone marrow can provide this complete package.
The second, yet very important issue is the fact that as of December of 2016, the FDA has made it very clear that adipose derived stem cell therapies are considered a drug and thus, they must now comply with the same strict protocols and pathways for the approval of this therapy through a drug trial. The use of adipose derived stem cells is now considered to be a therapy where the cells are more than minimally manipulated and the use of fat tissue within a joint is not considered to homologous use. Violation of these two principles, now automatically qualifies this treatment as a drug and any clinic or physician offering these therapies is now subject to an FDA investigation and more than likely a situation with eventual loss of ability to practice medicine. We we will leave this page available for search purposes to demonstrate our diverse experience with many forms of regenerative medicine, yet our respect for the laws of our country as well as safe and effective treatment for our patients.
Adipose Derived Stem Cell (ADSC) treatments are now only used in special circumstance cases such as patients with known bone diseases. Special arrangements for this procedure must be made. We do not normally provide this procedure as our first line of treatment for arthritis. The cost for this procedure is significantly higher and the time required for this procedure is also longer. Although Dr. Loniewski has had extensive experience with this procedure with excellent outcomes and safety profiles, we have found that the Bone Marrow Derived Stem Cell procedures have provided superior results with a lower cost and faster processing times.
What are they?
Adipose cells are your fat cells. These cells have small blood vessels that feed the cells and keep them alive. Within these vessels is a very rich supply of mesenchymal stem cells. These blood vessel cells can be concentrated into a small pellet called the stromal vascular fraction. This pellet not only contains the valuable stem cells, it also contains pericytes that help cells talk to each other and act like a normal functioning organ.
How does this work?
Currently, patients report to our office to ensure optimal sterility and quality control. Medical Assistants and technicians using highly regulated standard operating procedures ensure that you will have the safest procedure possible.
Most patients will not generally require the supervision of an anesthesiologist since the procedure is done through a simple local anesthetic fluid. Some patients will be administered oral Halcion or Valium (muscle relaxer) if necessary within a half hour of the procedure.
There is no need to start an IV or antibiotics since these will be given by mouth about an hour prior to the procedure. A small incision will be made on either side of the abdomen for entry of the local anesthetic. The abdominal area is numbed with a specially prepared fluid called tumescent fluid. A small liposuction tool called a Mercedes cannula is inserted. The liposuction is carefully performed in a fan wise motion on one side of the umbilicus removing only 30 to 60 cc of fatty tissue form each side of the abdomen to ensure even sculpting. However, the procedure is not designed to provide any aesthetic effect (it is not designed to make you look good). During this procedure, four to eight 10cc tubes of blood are taken for preparation of the platelet rich plasma. The fat cells are processed in a strict and regulated manner. A registered perfusionist, with training in this procedure, processes the adipose tissue and blood. He or she will follow the strict lab protocol for washing the fat cells and spinning these down to produce the stromal vascular fraction (SVF) layer containing the stem cells. During this process, the platelet rich plasma is also prepared yielding between 4-5 cc of the growth factor rich fluid. Think of the PRP as fertilizer and the stem cells as seeds. The two work with each other to provide a higher yield. The two are mixed together for the final process. The entire process is completed in one setting using a sterile hood, strict sterile technique, and a Current Good Manufacturing Process (cGMP). The final product is injected with a small amount of local anaesthetic into the joint(s) under sterile conditions. Patients are required to have someone drive them home because some patients may still feel tired from the muscle relaxant. The entire process will take between 2-3 hours. Most patients take it easy with no heavy lifting for about 1 week to protect the abdomen but the joint can be used normally in 24 hrs.
Although this is not a complete list, it is a general guideline to help you understand whom may be the ideal candidate for this procedure. You and your surgeon will always find exceptions since not every patient responds the same to each treatment:
• Patients looking for longer term pain relief of 4 or more years.
• Has enough abdominal fat to donate for the procedure.
• Mild to moderate arthritis of the joint based on x-rays although severe arthritic conditions may still benefit.
• No or limited instability symptoms of the joint (not more than 2 events per week).
• Lack of severe bowing of the joint.
• Lack of frequent severe joint swelling requiring needle aspirations (removing water from the knee)
• Lack of severe stiffness of the joint.
• Ability to stop anti-inflammatory medications (i.e. Motrin) for 2 weeks prior and 2 weeks after the procedure.
• Willing to participate in additional therapies to improve the health of the joint.
Safety of this Procedure
One of the best papers on the safety of this procedure comes from Pak, J in their paper entitled “ Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints.” 25 The authors concluded: “ Using both MRI tracking and telephone follow ups in 100 joints in 91 patients treated, no neoplastic complications were detected at any ADSC implantation sites. Based on our longitudinal cohort, the autologous and uncultured ADSCs/PRP therapy in the form of SVF could be considered to be safe when used as percutaneous local injections.” Another, more in-depth review surveying 100 private plastic surgical clinics, 68 plastic surgery departments at general and university hospitals, and 5 biotechnology companies by telephone. They found “ No toxicity resulting from residual collagenase or tumorigenicity associated with the ADSCs was observed.” 26 In summary, these studies revealed that this procedure does not cause cancer and there were no serious adverse reactions noted.
Is Adipose Derived Stem Cell Therapy Effective?
The purpose of this discussion is not to claim that this treatment cures or treats a specific condition, but to rather report the results of some previous studies.
Recent peer reviewed published studies also have some promising results. Yong-Gon Koh and his colleagues in S. Korea published an article entitled: “Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis”27. Dr. Koh treated thirty elderly patients, suffering from osteoarthritis of the knee with the same ADSC procedure and followed them closely for 2 years. He also took a second look of the knee through an arthroscopy in 16 of these patients. His published findings were the following: “Almost all patients showed significant improvement in all clinical outcomes at the final follow-up examination. All clinical results significantly improved at 2-year follow-up compared to 12-month follow-up (P\ 0.05). Among elderly patients aged (65 year)s, only five patients demonstrated worsening of Kellgren–Lawrence grade. On second-look arthroscopy, 87.5 % of elderly patients (14/16) improved or maintained cartilage status at least 2 years postoperatively. Moreover, none of the patients underwent total knee arthroplasty during this 2-year period. “ In plain English, this means that almost all the people in the study reduced their knee pain and increased their overall physical function over a 2 year period. A very interesting finding is the continued improvement over time. Patients not only improved from year 0 to year 1, but they also continued to improve further from year 1 to year two, showing continued improvement in almost all parameters. Best of all, none of the participants had their knee replaced. A sample picture of one patient in this study is included below. Picture “a” is the pre-procedure, “b” is the picture of the stem cells injected into the joint and “c” is the post procedure second look.
A controlled study comparing mesenchymal stem cells injections after an arthroscopy (common surgery used to treat cartilage tears of the knee) to a standard arthroscopy alone was published in 2010 by Dr. Varma in the Journal of the Indian Medical Assoc. 28 In this study, 50 patients with mild to moderate osteo-arthritis knee were selected and divided in two groups (group A and group B). Group A received arthroscopic debridement alone and group B received buffy coat (mesenchymal stem cell concentrate) injection along with the arthroscopic debridement of the knee. On follow-up, patients were assessed on the basis of visual analogue scale (VAS) score and osteo-arthritis outcome score, to compare results in both groups against each other to determine the efficacy of arthroscopic injection of buffy coat in the management of osteo-arthritis. The results suggest that the technique used in the study considerably improved the overall osteo-arthritis outcome score, especially the quality of life within the studied follow-up period and at the end of the follow-up. Although this study has some flaws in the reporting of the standardized testing, it reveals that stem cells are superior to a common treatment for degenerative arthritis.
Another study published in the prestigious Journal of Bone and Joint Surgery ( JBJS) , by C. Thomas Vangsness Jr, MD entitiled “Adult Human Mesenchymall Stem Cells Delivered via Intra- Articular Injection to the Knee Following Partial Medial Meniscectomy”. 29 introduced some interesting findings.This was a nicely designed double-blinded, placebo-controlled, randomized trial of the use of manufactured product of stem cells taken from someone else and injected into knees after a surgery was performed to remove a portion of the patients meniscus (which is a cartilage ring in the knee).The placebo group received a sodium hyaluronate (i.e. Supartz) injection and the intervention groups received different doses of the stem cells along with the sodium hyaluronate. Everyone was followed up with magnetic resonance images (MRI) and exams at six weeks, six months, one and two years. The MRI’s of the stem cell treatment groups revealed both an increase in the volume of regenerated meniscus tissue as well as a reduction of pain as compared to just the Supartz (hyluronate) injection over a two-year period without any adverse side effects. Although this is a different technique, this study does reveal that stem cell injections can increase tissue growth of the meniscus and reduce pain in arthritis of the knee better than a common injection used by many orthopedic surgeons for arthritis.
Another study published by Biomedical Research and Therapy, by Khanh Hong-Thien Bui and colleagues 31 at Ho Chi Minh University (obviously in Vietnam) also injected 21 patients with ADSC along with PRP and evaluated the patients pain and return of activities of living through questionnaires called the Visual Analog Scale (they rate their pain on a scale of 0-10) and the Lysholm score (asking how much pain, swelling, and instability they have as well as ability to climb stairs, squat and climb stairs). All of the 21 patients improved at 6 months.
The VAS pain score reduced on average from 7.6 to 1.5 and the Lysholm Score increased from 61 to 82. Furthermore pre and post MRI’s were reviewed and revealed that the cartilage layers were partially regenerated. There were no adverse reactions or side effects and 100% of the participants were happy with the treatment results. Although this study also has some flaws, it continues to provide some further evidence of efficacy in the short term.
How Long will this treatment last?
Patients rightfully ask this question. Here is some evidence to show that this is not a short term solution, but hopefully a long term solution. First, many of the studies above show results at 2 years and some as short as 6 months. However, this does not mean that the treatment stopped working at this interval. This merely means that the study was designed to stop at this point. If you look at some of these studies, there are some promising results showing positive structural reversal of the arthritic disease. For example, Koh et al in his arthroscopic second look study revealed reversal of the arthritic changes on visual inspection of the knee through arthroscopy. This finding was confirmed by the South Korean dosing study. In addition, Khanh Hong-Thien Bui and colleagues 31 found positive structural changes on serial MRI’s. Thus, we can conclude that this is not just a band aide type of treatment, but this evidence helps point us in the direction of positive reversal of the underlying destructive process of arthritis. This is unlike any other current treatment available in orthopedics.
A large multi-national, multi-center study evaluating patients of all ages with all levels of severity gives us some further evidence that this is a longer term treatment for arthritis. In the study by Michalek J, et al. entitled “Autologous adipose tissue-derived stromal vascular fraction cells in patients with osteoarthritis,”(Cell Transplant, 2015 Jan 20. doi: 10.3727)32 followed 1128 patients for up to 54 months (over 4 years). A majority of these patients (63%) had at least 75% improvement of pain and function and 91% had at least 50% improvement. However, obese patents and patients with more severe arthritis took longer to show this response. This is the largest and longest term study showing promising positive results in the longer term. Our own experience confirms this result. Our own unpublished close evaluation of pain and function using a visual analog scale and the WOMAC on hundreds of patients receiving a very similar procedure for over 2 years reveals similar results with an excellent safety profile and no serious adverse events.
Most of these studies have small numbers and some are not controlled, blinded, or randomized, but they do show a common pattern of:
• Reduction of pain.
• Restoration of function.
• High rate of patient satisfaction.
• Improved MRI or physical findings (microscopic or arthroscopic).
• Safe use with little or no side effects or adverse events.
Convenience of this Procedure:
Because this procedure is performed in a certified surgical center, you must come in to our office for a history and physical visit about one week prior. We ask that you start on a medication called doxycycline to help reduce enzymes that might injure the new cells. In addition, we also provide you with a tapered dose of special steroid called dexamethasone. This helps prevent an important type of stem cell from migrating out of the joint and into your spleen. You will arrive about 30 min prior to the start of your procedure at our office. You can eat a light meal prior to your procedure. The entire liposuction, processing and injection will take about 3 hours. Someone will drive you home if you take the relaxing medication. There is no need for formal physical therapy, but we do ask that you complete some simple exercises daily. Some patients are requested to use a brace for 2 months after the procedure. You can resume all your normal activities with the exception of abdominal exercises in 48 hours and resume all sporting activities in 3 months. Most patients do not notice any significant relief of symptoms for 3 months, so immediate pain relief, is not a benefit of this procedure.
Pain of the Procedure:
Overall, there has been very little or mild pain reported by patients undergoing this procedure. Most of the discomfort is mild and relates to some bruising of the abdomen from the liposuction. Most patients do not take the pain medications given to them. There is some spasm-like pain reported by patients during the injection into the joint. This resolves within 4-5 minutes.
At the current time, this procedure is not covered by any known insurance in the United States. Thus, we have been very sensitive to the cost of this procedure and we want to ensure the highest quality service with the safest possible environment. This includes:
- Evaluation by a board certified and fellowship trained orthopedic surgeon.
- Procedure performed by a board certified orthopedic surgeon.
- Preparation of the adipose derived stem cell injection along with platelet rich plasma by a certified and credentialed perfusionist.
- Sterile injection of the properly prepared and labeled cell mixture.
- Follow up calls by the surgical center to answer any questions or concerns.
With the above quality control process, there is a monetary cost and we try to keep these costs to a minimum. These expenses may be reimbursable through qualified Health Spending Accounts (HSA), Flexible Spending Account (FSA), Medical Savings Account (MSA), or Health Reimbursement Arrangement (HRA). Please contact your plan administrator for details. Deferred payment plans are available is you are interested. Our surgical scheduler can provide you with the details of this simple plan.
25 Pak, J et al. Safety reporting on implantation of autologous adipose tissue-derived stem cells with platelet-rich plasma into human articular joints.” Biomed Central Musculoskeletal Disorders, December 2013, 14:337.
26 Chang, H. et al Safety of adipose-derived stem cells in collagenase in fat tissue preparation. Aesthetic Plastic Surgery, 2013 August; 37(4):802-8.
27 Yong-Gon Koh et al. Clinical results and second-look arthroscopic findings after treatment with adipose-derived stem cells for knee osteoarthritis” Journal of Knee Surgery, Sports , Traumatology and Arthroscopy, December 2013.
28 Varma HS, The new avenues in the management of osteo-arthritis of knee--stem cells Journal of Indian Medical Association 2010 Sep;108(9):583-5.
29 Vangsness T et al. Adult Human Mesenchymall Stem Cells Delivered via Intra- Articular Injection to the Knee Following Partial Medial Meniscectomy Journal of Bone and Joint Surgery, 2014 Jan 15;96(2):90-8.
30 Jo Ch et al, Intra-articular injection of mesenchymal stem cells for the treatment of osteoarthritis of the knee: a proof-of-concept clinical trial. Stem Cells, 2014 May;32(5):1254-66. doi: 10.1002/stem.1634.
31 Khanh Hong-Thien Bui et al , Symptomatic knee osteoarthritis treatment using autologous adipose derived stem cells and platelet-rich plasma: a clinical study, Biomedical Research and Therapy, 2014 (1):02-08