About Dr Neil Riordan
Neil Riordan, PhD is the founder and chairman of Medistem Panama, Inc., (MPI) a leading stem cell laboratory and research facility located in the Technology Park at the prestigious City of Knowledge in Panama City, Panama. Founded in 2007, MPI stands at the forefront of applied research on adult stem cells for several chronic diseases. MPI's stem cell laboratory is ISO 9001 certified and fully licensed by the Panamanian Ministry of Health. Dr. Riordan is the founder of Stem Cell Institute (SCI) in Panama City, Panama (est. 2007).
Under the umbrella of MPI subsidiary Translational Biosciences, MPI and SCI are currently conducting five IRB-approved clinical trials in Panama for multiple sclerosis, rheumatoid arthritis and osteoarthritis using human umbilical cord-derived mesenchymal stem cells, mesenchymal trophic factors and stromal vascular fraction. Additional trials for spinal cord injury, autism and cerebral palsy are slated to commence in 2014 upon IRB approval.
Dr. Riordan’s research team collaborates with a number of universities and institutions, including National Institutes of Health, Indiana University, University of California, San Diego, University of Utah, University of Western Ontario, and University of Nebraska.
Dr. Riordan has published over 60 scientific articles in international peer-reviewed journals and authored two book chapters on the use of non-controversial stem cells from placenta and umbilical cord. In the stem cell arena, he and his colleagues have published more than 20 articles on Multiple Sclerosis, Spinal Cord Injury, Heart Failure, Rheumatoid Arthritis, Duchenne Muscular Dystrophy, Autism, and Charcot Marie Tooth Syndrome. In 2007, Dr. Riordan’s research team was the first to discover and document the existence of mesenchymal-like stem cells in menstrual blood. For this discovery, his team was honored with the “Medical Article of the Year Award” from Biomed Central. Other notable journals in which Dr. Riordan has published articles include the British Journal of Cancer, Cellular Immunology, Journal of Immunotherapy, and Translational Medicine.
Dr. Riordan is an accomplished inventor; listed on more the 25 patent families, including 11 issued patents. He is credited with a number of novel discoveries in the field of cancer research since the mid-1990s when he collaborated with his father Dr. Hugh Riordan on the effects of high-dose intravenous vitamin C on cancer cells and the tumor microenvironment. This pioneering study on vitamin C’s preferential toxicity to cancer cells notably led to a 1997 patent grant for the treatment of cancer with vitamin C. In 2010, Dr. Riordan received another patent for a new cellular cancer vaccine.
Regarding plans for the U.S., I have thankfully partnered with Dr. Wade McKenna, who is Board Certified in Orthopedic surgery and Fellowship trained in Trauma and Trauma Reconstructive Surgery. Dr. McKenna has more experience using bone marrow concentrate for orthopedic conditions that anyone I know. We are opening a regenerative orthopedic center in the Dallas area hopefully by mid-April of this year. It will be in a new building and is being built out now. The center is called the Riordan McKenna Institute. It is located in Southlake, Texas, which is between Dallas and Ft. Worth, very near DFW airport.
Contact Information:
Email: riordan@medistemresearch.com
Website for Stem Cell Institute: www.cellmedicine.com
Phone number for Stem Cell Institute: 1 800 980 7836.
Website for our clinical trials: www.translationalbiosciences.com
Questions & Answers
Q: I have heard from patients that you are doing intralymphatic stem cell injections. I think there are a lot of IntraLymph studies on other things like allergies, but none on stem cells that I can find. What is the reasoning behind this new route of administration? If stem cells get stuck in the lungs and we worry about that, why inject them directly into the lymph system where they would go to the spleen?
A.The goal of our treatments umbilical cord mesenchymal stem cells for patients with multiple sclerosis really has nothing to do with repairing the damaged or destroyed myelin in the lesions found in the brain and spinal cord. Because multiple sclerosis is first and foremost an autoimmune disease our goal is to address the immune dysfunction. At the root of the disease is a pool of immune cells called T-cells, which actively proliferate, cross the blood brain barrier, and attack myelin. Our primary goal then is to interfere with myelin-specific T-cell reproduction (something called “clonal expansion’). Mesenchymal stem cells (MSCs) have been shown in multiple studies to have the capacity to block this so-called clonal expansion of activated T cells. In a way MSCs immunosuppress, but unlike some drugs that suppress the immune system this specific blocking of activated T cells does not quash the entire immune system—the cells and their secretions only block the clonal expansion. Other drugs that suppress the immune system—for example hydrocortisone—have an effect on the entire immune system, which can increase the risk of the recipient to infectious diseases and even some cancers.
If it were the goal of the treatment to induce remyelination then certainly the route of delivery would be of greatest importance. You would want for the cells (or whatever proposed remyelination agent) to be as close to the lesions requiring the repair as possible. So I understand the rationale for the question.
In my opinion it will be difficult to successfully treat multiple sclerosis by remyelination alone because if you do not address the immune problem you will continue to lose myelin. Therefore, getting the cells to the lesions for myelin repair is not particularly important. Further support for this opinion is that there is very good evidence that the body has the innate ability to regenerate myelin without intervention. There are two good examples of this. The first example comes from a condition called Guillain–Barré syndrome. The syndrome is an autoimmune disease that results from an immune attack on the myelin of peripheral nerves. There is an ascending paralysis and the condition can be life threatening if the paralysis gets high enough to affect breathing. It is treatable and generally temporary. In 80% of the patients the underlying nerves are not irreparably damaged and there will be no long-term neurologic symptoms. 20% experience permanent nerve damage because the axons of the nerves are damaged. The good news is that the disease is temporary. The better news is that in the mild cases in which the axons were not destroyed, complete remyelination occurs—the body has the capacity to restore myelin.
The second example comes from a phenomenon seen with serial MRI images of the brains in people with MS. Fifty percent of these low intensity lesions known as “black holes” revert within one month of appearance, indicating that remyelination has occurred spontaneously.
Further support for the “treat the immune system and not the Central Nervous System” in MS comes from the work of several groups, including Northwestern University who are using chemotherapeutic “conditioning”, ie. wiping out the immune system (and the by-standing hematopoietic stem cells) followed by bone marrow reconstitution using previously harvested bone marrow stem cells. There are published results of many cases improving without anything having been done to address the myelin loss.
To the question of intra-lymphatic injections: There has been no work on “intra-lymphatic” injections. We are looking into peri-lymphatic (near the lymph nodes) injections of huMSCs for patients who are refractory to intravenous treatment.
Here is a little background on this subject: Dr. Arnold Caplan of Case Western Reserve, the scientist to first describe mesenchymal stem cells, was in Panama last year consulting with us. He also presented at a conference that we cosponsored. In one of my discussions with Dr. Caplan he casually mentioned that whenever they injected mesenchymal stem cells into the abdominal cavity of animals that did not have an active inflammatory process in there in the cavity the MSC’s would automatically go to the abdominal lymph chains. They were able to determine this because they use cells that were labeled with the florescent probe. I found this very interesting given that the 70-80% of the immune cells of your body reside in the abdominal cavity in and around the intestines.
The rationale for peri-lymphatic treatment is relatively simple. Firstly, the goal of therapy in autoimmune disease is to induce immune tolerance in the face of immune intolerance. The majority of the immune cells are found in the lymphatic (which includes the lamina propria) system of the gut. MCSs will, when lacking a more compelling inflammatory signal, migrate to the lymph nodes. Once in the lymph nodes they will migrate and interact with the immune cells (T-cells and T-cell priming dendritic cells). We know for a fact that MSCs interfere with dendritic cell priming of T-cells.
My book will be coming out in April. It will go into greater detail on this subject and many more. There are case histories as well as treatment protocols and rationale for each condition. Information about how to get the book “Mesenchymal Stem Cells: Nature’s Pharmacy” will be on www.Riordanbooks.com, as well as on www.amazon.com.
Q: I am a parent of children, ages 2 and 5 with autism spectrum disorder. Do you think stem cell treatment would help and if so what kind of treatment would you suggest?
A: We are studying whether or not intravenous human umbilical cord expanded mesenchymal stem cells (huMSCs) will help children on the autism spectrum. In cooperation with Dr. Sandy Lowe in New York we are just completing a prospective analysis of 14 case series of autism patients who were treated with 4 series of umbilical cord MSCs. We are analyzing the data from those who have completed treatment at the moment. Those patients were treated serially on 4 occasions, 3 months apart with 4 IV infusion of donor UC MSCs. So far 7 of the patients have completed the trial, the other 7 are expected to finish by May of 2014. Initial data back on suppression of the inflammatory cytokines that are very prominent in people with autism and the stop and reduction of the inflammatory cytokines can help with the disease process. Initial quantitative EEG data on each patient in the trial are also being analyzed. The Autism Treatment Evaluation Checklist (ATEC—www.autism.com) scores are trending toward improvement in the cohort and are vastly improved in some individual cases. I will send the paper to Barbara when it comes out. We hope to submit for publication an article describing the effect of the cells by the middle of 2014.
For the person asking the question, as with anyone looking for medical advice for an individual (or individuals), I would suggest they contact our doctors and discuss the protocols with them to see if their children are candidates for treatment.
Q: I have CIDP with secondary axonal. My main question - Is there a way to inject stemcells in the spinal fluid to rebuild nerves and reconnect with muscles? If so, what is the best type of treatment - mesenchymal, umbilical cord or embryonic?
A: CIDP is the result of demyelination of peripheral nerves. It is actually the end result of Guillain–Barré syndrome that did not remyelinate, or the 20% of GB patients who do not recover. Stem cells can be injected into the spinal cord. The question of whether or not they will rebuild or repair the damaged axons has not been answered to my knowledge.
Q: Any estimate of how many (%) of IV MSC's make it past the blood brain barrier to the area that MS patients need treated? I realize this is a very ambiguous question, but would like an opinion.
A: Without the use of an agent to open the blood brain barrier (BBB), and in the absence of a defect in the BBB, the likelihood is of any passing is low. Please see my answer to question number one. The goal of treating the immunologic dysfunction found in MS patients does not require any cells to pass the BBB.
Q: Do you use all types of these stem cell applications—stromal vascular fraction and autologous and umbilical? If so, how do you decide which to use for a person?
A: Our doctors have used the patient’s own stromal vascular fraction (SVF) for several years for autoimmune and orthopedic conditions. To my knowledge we were to first to use SVF in humans. Dr. Bob Harman, the CEO of Vet-Stem has been using SVF in animals in the U.S. for years. It is a bit ironic that your dog, cat, or even horse can get this treatment in the U.S. but FDA is taking the position that your own cells are a new drug because an enzyme (found in nature) is used to isolate the cells, and you put the cells back in a different place than you found them (non-homologous use). Bob and I have had many conversations over the years. The first use of SVF in humans was a lady from the U.S.—the wife of a doctor who refers patients to us. She suffered from rheumatoid arthritis. She had a very good response to treatment. Prior to them coming to the clinic Bob had told me about a dog that had a disease similar to rheumatoid arthritis and had responded very well to intravenous SVF. I put the doctor on the phone with Bob and after our Ethical Review Committee approved the protocol, she was treated. Subsequently we started treating MS patients with a combination of SVF and umbilical cord cells. The two main points of rationale were that you could obtain such large numbers of MSCs from a single liposuction at a relatively low cost (at the time cultured MSCs were much more expensive to isolate and expand) and that the SVF had worked on the patient with rheumatoid arthritis which at it’s core has a very similar immune dysregulation. We wrote up the first three successive cases and submitted the manuscript for publication. All three patients had a very good response to the treatment, and had no side effects from the intravenous cell treatment (bruising from the liposuction though) and had follow up MRIs. The article, which includes follow up MRIs, can be found here: http://www.translational-medicine.com/content/7/1/29. We also wrote up a case of a lady with rheumatoid arthritis who continues to do very well without further treatment more than 5 years after her single treatment. That article can be found here: http://www.intarchmed.com/content/5/1/5.
It is up to the treating physicians which protocol to use. In the case of stromal vascular fraction (SVF) firstly the patient needs to be healthy enough to undergo a liposuction. The doctors also consider the age and co-morbidities (other diseases or conditions) of the patients since both can decrease the number and functionality of the MSCs from the patient. We are currently comparing, retrospectively, the clinical outcomes from patients who have received SVF versus huMSCs for both multiple sclerosis and rheumatoid arthritis. We plan on writing an article for publication on that comparison in the near future. There have been some very good responses in patients just using donor umbilical cord cells. There are two very good reasons for using umbilical cells—they are vetted, young, and robust, and they are off the shelf and do not require the patient to undergo liposuction. We are also starting two prospective studies in parallel, which will compare the outcomes of autologous SVF against huMSCs in patients with rheumatoid arthritis.
We currently have protocols for stromal vascular fraction for treating patients with rheumatoid and osteoarthritis.
For spinal cord injury we use a combination of the patient’s own bone marrow cells and huMSCs, both intravenously and intrathecally (into the spinal fluid).
Regarding SVF, I would like to make one more point regarding same day SVF treatments that are being offered by more and more clinics in U.S. and other countries. These clinics are often representing that they are doing the same treatments that we do at a lower price, oftentimes citing our articles as rationale for treatment. The problems are three-fold. Firstly you cannot possible ensure that the SVF is free of microbial contamination without a 7 day culture. Dr. Caplan who I mentioned earlier famously said in regard to same day treatments, “Same Day, No Way.” Secondly, the amount of liposuctioned material is typically 12% of the amount of product we isolate cells from. In conclusion, most same day clinics are not performing the same procedure, nor performing the quality controls that are done in Panama at our facilities. Thirdly, and most importantly in the case of intravenous treatments (usually for autoimmune diseases), is that MSCs very actively home to areas of inflammation. If you have just had a liposuction and you receive cells intravenously, the cells are going to head right back to the fat was removed and not have much of a chance to interact with the immune cells that are causing the problem. If SVF is used intravenously in our clinic, the patient waits for one week so their liposuction wounds have time to heal and their SVF can be appropriately tested for sterility. SVF treatments that patients receive in facilities doing same day procedures cannot be compared to SVF treatments done at our facility.
Q: Are there some conditions such as neurological ones that respond better when the cells are greatly expanded? Is a high quantity essential for success or is that something that may be more of a selling point at some clinics? I have also seen this advertised for COPD and other conditions. It's almost like the more cells the better, but I would like your opinion.
A: That really depends on the quality of the cells after expansion. If they are still robust, not senescent, and still have a good secretion profile, then the more the better may be useful up to a point. If you take a small pool of starter cells and expand them to exhaustion, then I don’t think you are going to have a very good product. The MSCs used in Panama are not expanded beyond passage 5—a point at which there is no senescence in the population and they have a robust cytokine secretion profile. In order to use only cells that meet our release criteria, cells from approximately one (1.2 to be exact) out of 10 donated umbilical cords are used.
Contrast that to cells from a patient’s own fat tissue that are expanded. Firstly, the starting cells may, and many times are not very robust—they secrete little or no beneficial cytokines or chemokines, and must be expanded to hilt in order to hit the cell number. Please see my answer to number 7 for more on this subject.
This brings up a slightly different, yet related topic. There has been a lot of talk at recent meetings about more defined endpoints for the cells being used, and I couldn’t agree more. There are MSCs from bone marrow, menstrual blood, fat tissue, umbilical cord (even different parts of the umbilical cord—around the blood vessels, from the Wharton’s jelly, from the subepithelium, from the cord blood itself—which are most likely contaminants from a bruised placenta rather than the blood), teeth, amniotic membrane, amniotic fluid just to name sources in the “we didn’t mess with mother nature” adult stem cell world. Add to that the infinite variables when you consider the age and physical condition of the donor, particularly when using adipose or bone marrow as a source material and we, as a field, could be saying almost anything by using the term, “mesenchymal stem cell.” I think it is time that there is standardization in the field beyond the current definition of expressing/not expressing certain surface markers and the ability to differentiate into fat, bone, and cartilage. That standardization could come from using endpoints such as “remaining proliferative capacity (the number of doublings achievable in culture from the treatment cell bank), the secretome, even if there is standardization of one or two molecules, such as HGF, or one of the prostaglandins.
In the future I believe the field will take it a step further by measuring, even by a surrogate marker, the potential effects of the cells on the target condition. In the case of autoimmunity the cells and their secretions could be tested for their capacity to modulate the immune system. In the case of inflammatory conditions, the cells and their secretions could be tested for the ability to control or block inflammation.
Q: Do you use HGF and other growth factors in your treatments? If so, have you done any studies with HGF?
A: Our license from the Panamanian Ministry of Health is for adult stem cells and stem cell products. We have tested the secretome (the molecules that are secreted from the cells) of our umbilical cord MSCs from our laboratory and have found that they do secrete HGF (hepatocyte growth factor) in significant quantities. HGF is one of the MSC-secreted molecules responsible for the cell’s protection of the liver from radiation damage. http://www.ncbi.nlm.nih.gov/pubmed/24369528
There was a recent article from Case Western Reserve that showed that the secretions of MSCs (conditioned medium) was effective in treating a mouse model of multiple sclerosis. The conditioned medium contained HGF. When they blocked the HGF the beneficial effect of the medium went to zero. So HGF secretion by MSCs looks to be quite an important topic.
http://www.ncbi.nlm.nih.gov/pubmed/22610068
We have been studying the MSC’s from the adipose tissue of patients with multiple sclerosis for several years now. Our data are similar to those just published in the bone marrow arena. We found that the cells from people with MS have a decreased capacity to replicate in culture, they have a decreased capacity for secretion cytokines (including HGF), and their level of senescence is much higher than people without MS or other autoimmune diseases.
Interestingly, there is a new article out in which they looked at the MSCs from multiple sclerosis patients. The MSCs were taken from their bone marrow prior to the patients undergoing a bone marrow transplant. And what they found was that the cells from the bone marrow did not divide, and the cells had a greatly decreased capacity to produce HGF.
http://www.ncbi.nlm.nih.gov/pubmed/24256874
In addition to the HGF produced by the MSCs themselves, there is also evidence showing that the transplantation of umbilical MSCs can stimulate the production of HCF stem cells found in diseased renal tissue in mice. http://www.ncbi.nlm.nih.gov/pubmed/23734757
Q: Dr. Riordan - Your clinic is considered "offshore". In the U.S. there is an elitist attitude that warns patients of the risks of offshore clinics. I see that you do clinical studies, you are the son of a respected researcher, you have written many papers, far more than many researchers in the U.S. have and yet you still come under fire. How do you respond to this criticism?
A: When I spoke at and IFATS (International Federation for Adipose Therapeutics and Science) meeting a few years ago, I was introduced by Dr. Spencer Brown, who at that time was at UT-Southwestern (now at McGowan Institute at Pittsburg). During the introduction Dr. Brown mentioned, much to his credit, that one of the reasons he invited me to speak was because he didn’t feel the “offshore” community was able to have a voice at their meetings.
Before my talk I jokingly corrected him by saying that Panama is technically not “offshore” since you can drive there from the U.S.
When I come under fire, I just try to keep my head down and keep working. The only people we seem to “come under fire” from are those with a vested interest in not seeing what we do become more commonplace. The worst example is a blogging critic (I think we all know his name) who has no credentials in science or bioethics, and works for a company (public/private conglomerate) that has more to lose than any other entity on the planet if what we are doing in Panama becomes a part of mainstream medicine. The entity in question has a vast amount of intellectual property (patents) on iPS cells, or induced pluripotent stem cell technology. If off the shelf umbilical cord MSCs, and patients’ own fat or bone marrow derived stem cells provided to us in plentitude by Mother Nature are widely used, the value of iPS cells will greatly diminish.
I also find it interesting that, with the exception of the person mentioned above who has no scientific training, the most vocal critics are Ph.D.’s in academia without medical degrees or medical training. These are people who have never been in the medical trenches. People who have never had to look a patient (or hundreds of patients) with a terminal or intractable disease in the eye and say, “Wait until it is FDA approved.” It’s quite easy and safe to say “That treatment hasn’t been approved by the FDA so don’t do it.”
In my mind the most inappropriate critics are those who paint everyone performing treatments with adult stem cells with the same brush. In comparison to most other treatment facilities our organization is quite different. As you mentioned we publish our data (not necessary as much as we and others would like to). We collaborate with several Universities. On our SVF/MS paper alone our co-authors were from University of California, San Diego, Indiana University, University of Western Ontario, and the University of Utah. Our BSL-2 laboratory is fully licensed by the Ministry of Health, is cGMP and cGLP compliant, and ISO-9001 certified. We are in the process of beginning clinical trials approved by the National Bioethics Committee of Panama. The first five studies were approved and can be found on the NIH site www.clinicaltrials.gov. We are transparent—not only in our publications that describe in detail what we do and how we do it, but also by allowing anyone in academia to visit our facilities. We have had multiple visits from physicians and researchers from all over the world. Doctors from The University of Miami, Project Cure for Paralysis visited us several times and even reviewed many of our spinal cord injury patient charts. Another major difference is the fact that we accept a minority of patients who apply for treatment. We have strict inclusion and exclusion criteria. Given the above examples, I don’t think you can paint us with the same brush as everyone else in the field.
Regarding my father, we worked together for many years. The biggest contribution of our collaboration came from of our studies of the effects of high dose intravenous vitamin C on malignancy. We were the first to demonstrate that vitamin C, in high enough doses, could act similarly to chemotherapy in a non-toxic way. We showed that levels of vitamin C could be achieved in the blood of cancer patients high enough to selectively kill cancer cells. Many physicians continue to use the “Riordan Protocol” to treat cancer patients. There was plenty of ridicule and opposition to our work. Our paradigm-changing article was published in 1995. Prior to 1995 no prospective trials of intravenous vitamin C had been done. Now, in 2014, five prospective clinical trials have been completed and seven trials currently are currently recruiting patients on http://clinicaltrials.gov. The trials are being done at such Universities as Thomas Jefferson and Kansas University.
If readers are interested in reading more, here is the website that chronicles our intravenous vitamin C work: http://www.neilriordanivc.com. The Riordan Protocol can be found here: http://neilriordanivc.com/wp-content/uploads/2013/04/Clinical-Protocol-Riordan-IVC.pdf.
My father wrote a trilogy of books entitled “Medical Mavericks” in which he chronicled the history of innovations in medicine. The innovations were ahead of their time. The moral of the vignettes is that, in spite of professional and in some cases literal tarring and feathering of medical innovators, the truth usually comes out and the concepts/therapies become mainstream. As Arthur Schopenhauer said, “All truth passes through three stages: First, it is ridiculed; Second, it is violently opposed; Third, it is accepted as self-evident.” Hopefully I’ll be around for the third phase of the truth about adult stem cells.
Q: If the FDA loosens regulations in the U.S., do you have any plans to open a clinic here?
A: Unfortunately I don’t see FDA loosening regulations any time soon so I have no plans to do anything in the U.S. using umbilical cord MSCs or even autologous SVF in the near future.
It would be great if the U.S. would follow Japan’s lead. The Japanese parliament passed legislation in November of last year that essentially allows a company to market a cell product after the product has been demonstrated to be safe. Quoting from an Athersys press release: “Recently, Japan's parliament enacted new legislation to promote the safe and accelerated development of treatments using stem cells. The new regenerative medicine law and revised pharmaceutical affairs law define products containing stem cells as regenerative medicine products and allow for the conditional approval of such products if safety has been confirmed in clinical trials, even if their efficacy has not been fully demonstrated.”
So you can guess where everyone is running to and isn’t the U.S. Here are press releases from Mesoblast and Athersys, respectively: http://finance.yahoo.com/news/japanese-regenerative-medicine-legislation-commercial-001627681.html
http://finance.yahoo.com/news/athersys-announces-patents-japan-stem-120000430.html
Regarding plans for the U.S., I have thankfully partnered with Dr. Wade McKenna, who is Board Certified in Orthopedic surgery and Fellowship trained in Trauma and Trauma Reconstructive Surgery. Dr. McKenna has more experience using bone marrow concentrate for orthopedic conditions that anyone I know. We are opening a regenerative orthopedic center in the Dallas area hopefully by mid-April of this year. It will be in a new building and is being built out now. The center is called the Riordan McKenna Institute. It is located in Southlake, Texas, which is between Dallas and Ft. Worth, very near DFW airport.
Neil Riordan, PhD is the founder and chairman of Medistem Panama, Inc., (MPI) a leading stem cell laboratory and research facility located in the Technology Park at the prestigious City of Knowledge in Panama City, Panama. Founded in 2007, MPI stands at the forefront of applied research on adult stem cells for several chronic diseases. MPI's stem cell laboratory is ISO 9001 certified and fully licensed by the Panamanian Ministry of Health. Dr. Riordan is the founder of Stem Cell Institute (SCI) in Panama City, Panama (est. 2007).
Under the umbrella of MPI subsidiary Translational Biosciences, MPI and SCI are currently conducting five IRB-approved clinical trials in Panama for multiple sclerosis, rheumatoid arthritis and osteoarthritis using human umbilical cord-derived mesenchymal stem cells, mesenchymal trophic factors and stromal vascular fraction. Additional trials for spinal cord injury, autism and cerebral palsy are slated to commence in 2014 upon IRB approval.
Dr. Riordan’s research team collaborates with a number of universities and institutions, including National Institutes of Health, Indiana University, University of California, San Diego, University of Utah, University of Western Ontario, and University of Nebraska.
Dr. Riordan has published over 60 scientific articles in international peer-reviewed journals and authored two book chapters on the use of non-controversial stem cells from placenta and umbilical cord. In the stem cell arena, he and his colleagues have published more than 20 articles on Multiple Sclerosis, Spinal Cord Injury, Heart Failure, Rheumatoid Arthritis, Duchenne Muscular Dystrophy, Autism, and Charcot Marie Tooth Syndrome. In 2007, Dr. Riordan’s research team was the first to discover and document the existence of mesenchymal-like stem cells in menstrual blood. For this discovery, his team was honored with the “Medical Article of the Year Award” from Biomed Central. Other notable journals in which Dr. Riordan has published articles include the British Journal of Cancer, Cellular Immunology, Journal of Immunotherapy, and Translational Medicine.
Dr. Riordan is an accomplished inventor; listed on more the 25 patent families, including 11 issued patents. He is credited with a number of novel discoveries in the field of cancer research since the mid-1990s when he collaborated with his father Dr. Hugh Riordan on the effects of high-dose intravenous vitamin C on cancer cells and the tumor microenvironment. This pioneering study on vitamin C’s preferential toxicity to cancer cells notably led to a 1997 patent grant for the treatment of cancer with vitamin C. In 2010, Dr. Riordan received another patent for a new cellular cancer vaccine.
Regarding plans for the U.S., I have thankfully partnered with Dr. Wade McKenna, who is Board Certified in Orthopedic surgery and Fellowship trained in Trauma and Trauma Reconstructive Surgery. Dr. McKenna has more experience using bone marrow concentrate for orthopedic conditions that anyone I know. We are opening a regenerative orthopedic center in the Dallas area hopefully by mid-April of this year. It will be in a new building and is being built out now. The center is called the Riordan McKenna Institute. It is located in Southlake, Texas, which is between Dallas and Ft. Worth, very near DFW airport.
Contact Information:
Email: riordan@medistemresearch.com
Website for Stem Cell Institute: www.cellmedicine.com
Phone number for Stem Cell Institute: 1 800 980 7836.
Website for our clinical trials: www.translationalbiosciences.com
Questions & Answers
Q: I have heard from patients that you are doing intralymphatic stem cell injections. I think there are a lot of IntraLymph studies on other things like allergies, but none on stem cells that I can find. What is the reasoning behind this new route of administration? If stem cells get stuck in the lungs and we worry about that, why inject them directly into the lymph system where they would go to the spleen?
A.The goal of our treatments umbilical cord mesenchymal stem cells for patients with multiple sclerosis really has nothing to do with repairing the damaged or destroyed myelin in the lesions found in the brain and spinal cord. Because multiple sclerosis is first and foremost an autoimmune disease our goal is to address the immune dysfunction. At the root of the disease is a pool of immune cells called T-cells, which actively proliferate, cross the blood brain barrier, and attack myelin. Our primary goal then is to interfere with myelin-specific T-cell reproduction (something called “clonal expansion’). Mesenchymal stem cells (MSCs) have been shown in multiple studies to have the capacity to block this so-called clonal expansion of activated T cells. In a way MSCs immunosuppress, but unlike some drugs that suppress the immune system this specific blocking of activated T cells does not quash the entire immune system—the cells and their secretions only block the clonal expansion. Other drugs that suppress the immune system—for example hydrocortisone—have an effect on the entire immune system, which can increase the risk of the recipient to infectious diseases and even some cancers.
If it were the goal of the treatment to induce remyelination then certainly the route of delivery would be of greatest importance. You would want for the cells (or whatever proposed remyelination agent) to be as close to the lesions requiring the repair as possible. So I understand the rationale for the question.
In my opinion it will be difficult to successfully treat multiple sclerosis by remyelination alone because if you do not address the immune problem you will continue to lose myelin. Therefore, getting the cells to the lesions for myelin repair is not particularly important. Further support for this opinion is that there is very good evidence that the body has the innate ability to regenerate myelin without intervention. There are two good examples of this. The first example comes from a condition called Guillain–Barré syndrome. The syndrome is an autoimmune disease that results from an immune attack on the myelin of peripheral nerves. There is an ascending paralysis and the condition can be life threatening if the paralysis gets high enough to affect breathing. It is treatable and generally temporary. In 80% of the patients the underlying nerves are not irreparably damaged and there will be no long-term neurologic symptoms. 20% experience permanent nerve damage because the axons of the nerves are damaged. The good news is that the disease is temporary. The better news is that in the mild cases in which the axons were not destroyed, complete remyelination occurs—the body has the capacity to restore myelin.
The second example comes from a phenomenon seen with serial MRI images of the brains in people with MS. Fifty percent of these low intensity lesions known as “black holes” revert within one month of appearance, indicating that remyelination has occurred spontaneously.
Further support for the “treat the immune system and not the Central Nervous System” in MS comes from the work of several groups, including Northwestern University who are using chemotherapeutic “conditioning”, ie. wiping out the immune system (and the by-standing hematopoietic stem cells) followed by bone marrow reconstitution using previously harvested bone marrow stem cells. There are published results of many cases improving without anything having been done to address the myelin loss.
To the question of intra-lymphatic injections: There has been no work on “intra-lymphatic” injections. We are looking into peri-lymphatic (near the lymph nodes) injections of huMSCs for patients who are refractory to intravenous treatment.
Here is a little background on this subject: Dr. Arnold Caplan of Case Western Reserve, the scientist to first describe mesenchymal stem cells, was in Panama last year consulting with us. He also presented at a conference that we cosponsored. In one of my discussions with Dr. Caplan he casually mentioned that whenever they injected mesenchymal stem cells into the abdominal cavity of animals that did not have an active inflammatory process in there in the cavity the MSC’s would automatically go to the abdominal lymph chains. They were able to determine this because they use cells that were labeled with the florescent probe. I found this very interesting given that the 70-80% of the immune cells of your body reside in the abdominal cavity in and around the intestines.
The rationale for peri-lymphatic treatment is relatively simple. Firstly, the goal of therapy in autoimmune disease is to induce immune tolerance in the face of immune intolerance. The majority of the immune cells are found in the lymphatic (which includes the lamina propria) system of the gut. MCSs will, when lacking a more compelling inflammatory signal, migrate to the lymph nodes. Once in the lymph nodes they will migrate and interact with the immune cells (T-cells and T-cell priming dendritic cells). We know for a fact that MSCs interfere with dendritic cell priming of T-cells.
My book will be coming out in April. It will go into greater detail on this subject and many more. There are case histories as well as treatment protocols and rationale for each condition. Information about how to get the book “Mesenchymal Stem Cells: Nature’s Pharmacy” will be on www.Riordanbooks.com, as well as on www.amazon.com.
Q: I am a parent of children, ages 2 and 5 with autism spectrum disorder. Do you think stem cell treatment would help and if so what kind of treatment would you suggest?
A: We are studying whether or not intravenous human umbilical cord expanded mesenchymal stem cells (huMSCs) will help children on the autism spectrum. In cooperation with Dr. Sandy Lowe in New York we are just completing a prospective analysis of 14 case series of autism patients who were treated with 4 series of umbilical cord MSCs. We are analyzing the data from those who have completed treatment at the moment. Those patients were treated serially on 4 occasions, 3 months apart with 4 IV infusion of donor UC MSCs. So far 7 of the patients have completed the trial, the other 7 are expected to finish by May of 2014. Initial data back on suppression of the inflammatory cytokines that are very prominent in people with autism and the stop and reduction of the inflammatory cytokines can help with the disease process. Initial quantitative EEG data on each patient in the trial are also being analyzed. The Autism Treatment Evaluation Checklist (ATEC—www.autism.com) scores are trending toward improvement in the cohort and are vastly improved in some individual cases. I will send the paper to Barbara when it comes out. We hope to submit for publication an article describing the effect of the cells by the middle of 2014.
For the person asking the question, as with anyone looking for medical advice for an individual (or individuals), I would suggest they contact our doctors and discuss the protocols with them to see if their children are candidates for treatment.
Q: I have CIDP with secondary axonal. My main question - Is there a way to inject stemcells in the spinal fluid to rebuild nerves and reconnect with muscles? If so, what is the best type of treatment - mesenchymal, umbilical cord or embryonic?
A: CIDP is the result of demyelination of peripheral nerves. It is actually the end result of Guillain–Barré syndrome that did not remyelinate, or the 20% of GB patients who do not recover. Stem cells can be injected into the spinal cord. The question of whether or not they will rebuild or repair the damaged axons has not been answered to my knowledge.
Q: Any estimate of how many (%) of IV MSC's make it past the blood brain barrier to the area that MS patients need treated? I realize this is a very ambiguous question, but would like an opinion.
A: Without the use of an agent to open the blood brain barrier (BBB), and in the absence of a defect in the BBB, the likelihood is of any passing is low. Please see my answer to question number one. The goal of treating the immunologic dysfunction found in MS patients does not require any cells to pass the BBB.
Q: Do you use all types of these stem cell applications—stromal vascular fraction and autologous and umbilical? If so, how do you decide which to use for a person?
A: Our doctors have used the patient’s own stromal vascular fraction (SVF) for several years for autoimmune and orthopedic conditions. To my knowledge we were to first to use SVF in humans. Dr. Bob Harman, the CEO of Vet-Stem has been using SVF in animals in the U.S. for years. It is a bit ironic that your dog, cat, or even horse can get this treatment in the U.S. but FDA is taking the position that your own cells are a new drug because an enzyme (found in nature) is used to isolate the cells, and you put the cells back in a different place than you found them (non-homologous use). Bob and I have had many conversations over the years. The first use of SVF in humans was a lady from the U.S.—the wife of a doctor who refers patients to us. She suffered from rheumatoid arthritis. She had a very good response to treatment. Prior to them coming to the clinic Bob had told me about a dog that had a disease similar to rheumatoid arthritis and had responded very well to intravenous SVF. I put the doctor on the phone with Bob and after our Ethical Review Committee approved the protocol, she was treated. Subsequently we started treating MS patients with a combination of SVF and umbilical cord cells. The two main points of rationale were that you could obtain such large numbers of MSCs from a single liposuction at a relatively low cost (at the time cultured MSCs were much more expensive to isolate and expand) and that the SVF had worked on the patient with rheumatoid arthritis which at it’s core has a very similar immune dysregulation. We wrote up the first three successive cases and submitted the manuscript for publication. All three patients had a very good response to the treatment, and had no side effects from the intravenous cell treatment (bruising from the liposuction though) and had follow up MRIs. The article, which includes follow up MRIs, can be found here: http://www.translational-medicine.com/content/7/1/29. We also wrote up a case of a lady with rheumatoid arthritis who continues to do very well without further treatment more than 5 years after her single treatment. That article can be found here: http://www.intarchmed.com/content/5/1/5.
It is up to the treating physicians which protocol to use. In the case of stromal vascular fraction (SVF) firstly the patient needs to be healthy enough to undergo a liposuction. The doctors also consider the age and co-morbidities (other diseases or conditions) of the patients since both can decrease the number and functionality of the MSCs from the patient. We are currently comparing, retrospectively, the clinical outcomes from patients who have received SVF versus huMSCs for both multiple sclerosis and rheumatoid arthritis. We plan on writing an article for publication on that comparison in the near future. There have been some very good responses in patients just using donor umbilical cord cells. There are two very good reasons for using umbilical cells—they are vetted, young, and robust, and they are off the shelf and do not require the patient to undergo liposuction. We are also starting two prospective studies in parallel, which will compare the outcomes of autologous SVF against huMSCs in patients with rheumatoid arthritis.
We currently have protocols for stromal vascular fraction for treating patients with rheumatoid and osteoarthritis.
For spinal cord injury we use a combination of the patient’s own bone marrow cells and huMSCs, both intravenously and intrathecally (into the spinal fluid).
Regarding SVF, I would like to make one more point regarding same day SVF treatments that are being offered by more and more clinics in U.S. and other countries. These clinics are often representing that they are doing the same treatments that we do at a lower price, oftentimes citing our articles as rationale for treatment. The problems are three-fold. Firstly you cannot possible ensure that the SVF is free of microbial contamination without a 7 day culture. Dr. Caplan who I mentioned earlier famously said in regard to same day treatments, “Same Day, No Way.” Secondly, the amount of liposuctioned material is typically 12% of the amount of product we isolate cells from. In conclusion, most same day clinics are not performing the same procedure, nor performing the quality controls that are done in Panama at our facilities. Thirdly, and most importantly in the case of intravenous treatments (usually for autoimmune diseases), is that MSCs very actively home to areas of inflammation. If you have just had a liposuction and you receive cells intravenously, the cells are going to head right back to the fat was removed and not have much of a chance to interact with the immune cells that are causing the problem. If SVF is used intravenously in our clinic, the patient waits for one week so their liposuction wounds have time to heal and their SVF can be appropriately tested for sterility. SVF treatments that patients receive in facilities doing same day procedures cannot be compared to SVF treatments done at our facility.
Q: Are there some conditions such as neurological ones that respond better when the cells are greatly expanded? Is a high quantity essential for success or is that something that may be more of a selling point at some clinics? I have also seen this advertised for COPD and other conditions. It's almost like the more cells the better, but I would like your opinion.
A: That really depends on the quality of the cells after expansion. If they are still robust, not senescent, and still have a good secretion profile, then the more the better may be useful up to a point. If you take a small pool of starter cells and expand them to exhaustion, then I don’t think you are going to have a very good product. The MSCs used in Panama are not expanded beyond passage 5—a point at which there is no senescence in the population and they have a robust cytokine secretion profile. In order to use only cells that meet our release criteria, cells from approximately one (1.2 to be exact) out of 10 donated umbilical cords are used.
Contrast that to cells from a patient’s own fat tissue that are expanded. Firstly, the starting cells may, and many times are not very robust—they secrete little or no beneficial cytokines or chemokines, and must be expanded to hilt in order to hit the cell number. Please see my answer to number 7 for more on this subject.
This brings up a slightly different, yet related topic. There has been a lot of talk at recent meetings about more defined endpoints for the cells being used, and I couldn’t agree more. There are MSCs from bone marrow, menstrual blood, fat tissue, umbilical cord (even different parts of the umbilical cord—around the blood vessels, from the Wharton’s jelly, from the subepithelium, from the cord blood itself—which are most likely contaminants from a bruised placenta rather than the blood), teeth, amniotic membrane, amniotic fluid just to name sources in the “we didn’t mess with mother nature” adult stem cell world. Add to that the infinite variables when you consider the age and physical condition of the donor, particularly when using adipose or bone marrow as a source material and we, as a field, could be saying almost anything by using the term, “mesenchymal stem cell.” I think it is time that there is standardization in the field beyond the current definition of expressing/not expressing certain surface markers and the ability to differentiate into fat, bone, and cartilage. That standardization could come from using endpoints such as “remaining proliferative capacity (the number of doublings achievable in culture from the treatment cell bank), the secretome, even if there is standardization of one or two molecules, such as HGF, or one of the prostaglandins.
In the future I believe the field will take it a step further by measuring, even by a surrogate marker, the potential effects of the cells on the target condition. In the case of autoimmunity the cells and their secretions could be tested for their capacity to modulate the immune system. In the case of inflammatory conditions, the cells and their secretions could be tested for the ability to control or block inflammation.
Q: Do you use HGF and other growth factors in your treatments? If so, have you done any studies with HGF?
A: Our license from the Panamanian Ministry of Health is for adult stem cells and stem cell products. We have tested the secretome (the molecules that are secreted from the cells) of our umbilical cord MSCs from our laboratory and have found that they do secrete HGF (hepatocyte growth factor) in significant quantities. HGF is one of the MSC-secreted molecules responsible for the cell’s protection of the liver from radiation damage. http://www.ncbi.nlm.nih.gov/pubmed/24369528
There was a recent article from Case Western Reserve that showed that the secretions of MSCs (conditioned medium) was effective in treating a mouse model of multiple sclerosis. The conditioned medium contained HGF. When they blocked the HGF the beneficial effect of the medium went to zero. So HGF secretion by MSCs looks to be quite an important topic.
http://www.ncbi.nlm.nih.gov/pubmed/22610068
We have been studying the MSC’s from the adipose tissue of patients with multiple sclerosis for several years now. Our data are similar to those just published in the bone marrow arena. We found that the cells from people with MS have a decreased capacity to replicate in culture, they have a decreased capacity for secretion cytokines (including HGF), and their level of senescence is much higher than people without MS or other autoimmune diseases.
Interestingly, there is a new article out in which they looked at the MSCs from multiple sclerosis patients. The MSCs were taken from their bone marrow prior to the patients undergoing a bone marrow transplant. And what they found was that the cells from the bone marrow did not divide, and the cells had a greatly decreased capacity to produce HGF.
http://www.ncbi.nlm.nih.gov/pubmed/24256874
In addition to the HGF produced by the MSCs themselves, there is also evidence showing that the transplantation of umbilical MSCs can stimulate the production of HCF stem cells found in diseased renal tissue in mice. http://www.ncbi.nlm.nih.gov/pubmed/23734757
Q: Dr. Riordan - Your clinic is considered "offshore". In the U.S. there is an elitist attitude that warns patients of the risks of offshore clinics. I see that you do clinical studies, you are the son of a respected researcher, you have written many papers, far more than many researchers in the U.S. have and yet you still come under fire. How do you respond to this criticism?
A: When I spoke at and IFATS (International Federation for Adipose Therapeutics and Science) meeting a few years ago, I was introduced by Dr. Spencer Brown, who at that time was at UT-Southwestern (now at McGowan Institute at Pittsburg). During the introduction Dr. Brown mentioned, much to his credit, that one of the reasons he invited me to speak was because he didn’t feel the “offshore” community was able to have a voice at their meetings.
Before my talk I jokingly corrected him by saying that Panama is technically not “offshore” since you can drive there from the U.S.
When I come under fire, I just try to keep my head down and keep working. The only people we seem to “come under fire” from are those with a vested interest in not seeing what we do become more commonplace. The worst example is a blogging critic (I think we all know his name) who has no credentials in science or bioethics, and works for a company (public/private conglomerate) that has more to lose than any other entity on the planet if what we are doing in Panama becomes a part of mainstream medicine. The entity in question has a vast amount of intellectual property (patents) on iPS cells, or induced pluripotent stem cell technology. If off the shelf umbilical cord MSCs, and patients’ own fat or bone marrow derived stem cells provided to us in plentitude by Mother Nature are widely used, the value of iPS cells will greatly diminish.
I also find it interesting that, with the exception of the person mentioned above who has no scientific training, the most vocal critics are Ph.D.’s in academia without medical degrees or medical training. These are people who have never been in the medical trenches. People who have never had to look a patient (or hundreds of patients) with a terminal or intractable disease in the eye and say, “Wait until it is FDA approved.” It’s quite easy and safe to say “That treatment hasn’t been approved by the FDA so don’t do it.”
In my mind the most inappropriate critics are those who paint everyone performing treatments with adult stem cells with the same brush. In comparison to most other treatment facilities our organization is quite different. As you mentioned we publish our data (not necessary as much as we and others would like to). We collaborate with several Universities. On our SVF/MS paper alone our co-authors were from University of California, San Diego, Indiana University, University of Western Ontario, and the University of Utah. Our BSL-2 laboratory is fully licensed by the Ministry of Health, is cGMP and cGLP compliant, and ISO-9001 certified. We are in the process of beginning clinical trials approved by the National Bioethics Committee of Panama. The first five studies were approved and can be found on the NIH site www.clinicaltrials.gov. We are transparent—not only in our publications that describe in detail what we do and how we do it, but also by allowing anyone in academia to visit our facilities. We have had multiple visits from physicians and researchers from all over the world. Doctors from The University of Miami, Project Cure for Paralysis visited us several times and even reviewed many of our spinal cord injury patient charts. Another major difference is the fact that we accept a minority of patients who apply for treatment. We have strict inclusion and exclusion criteria. Given the above examples, I don’t think you can paint us with the same brush as everyone else in the field.
Regarding my father, we worked together for many years. The biggest contribution of our collaboration came from of our studies of the effects of high dose intravenous vitamin C on malignancy. We were the first to demonstrate that vitamin C, in high enough doses, could act similarly to chemotherapy in a non-toxic way. We showed that levels of vitamin C could be achieved in the blood of cancer patients high enough to selectively kill cancer cells. Many physicians continue to use the “Riordan Protocol” to treat cancer patients. There was plenty of ridicule and opposition to our work. Our paradigm-changing article was published in 1995. Prior to 1995 no prospective trials of intravenous vitamin C had been done. Now, in 2014, five prospective clinical trials have been completed and seven trials currently are currently recruiting patients on http://clinicaltrials.gov. The trials are being done at such Universities as Thomas Jefferson and Kansas University.
If readers are interested in reading more, here is the website that chronicles our intravenous vitamin C work: http://www.neilriordanivc.com. The Riordan Protocol can be found here: http://neilriordanivc.com/wp-content/uploads/2013/04/Clinical-Protocol-Riordan-IVC.pdf.
My father wrote a trilogy of books entitled “Medical Mavericks” in which he chronicled the history of innovations in medicine. The innovations were ahead of their time. The moral of the vignettes is that, in spite of professional and in some cases literal tarring and feathering of medical innovators, the truth usually comes out and the concepts/therapies become mainstream. As Arthur Schopenhauer said, “All truth passes through three stages: First, it is ridiculed; Second, it is violently opposed; Third, it is accepted as self-evident.” Hopefully I’ll be around for the third phase of the truth about adult stem cells.
Q: If the FDA loosens regulations in the U.S., do you have any plans to open a clinic here?
A: Unfortunately I don’t see FDA loosening regulations any time soon so I have no plans to do anything in the U.S. using umbilical cord MSCs or even autologous SVF in the near future.
It would be great if the U.S. would follow Japan’s lead. The Japanese parliament passed legislation in November of last year that essentially allows a company to market a cell product after the product has been demonstrated to be safe. Quoting from an Athersys press release: “Recently, Japan's parliament enacted new legislation to promote the safe and accelerated development of treatments using stem cells. The new regenerative medicine law and revised pharmaceutical affairs law define products containing stem cells as regenerative medicine products and allow for the conditional approval of such products if safety has been confirmed in clinical trials, even if their efficacy has not been fully demonstrated.”
So you can guess where everyone is running to and isn’t the U.S. Here are press releases from Mesoblast and Athersys, respectively: http://finance.yahoo.com/news/japanese-regenerative-medicine-legislation-commercial-001627681.html
http://finance.yahoo.com/news/athersys-announces-patents-japan-stem-120000430.html
Regarding plans for the U.S., I have thankfully partnered with Dr. Wade McKenna, who is Board Certified in Orthopedic surgery and Fellowship trained in Trauma and Trauma Reconstructive Surgery. Dr. McKenna has more experience using bone marrow concentrate for orthopedic conditions that anyone I know. We are opening a regenerative orthopedic center in the Dallas area hopefully by mid-April of this year. It will be in a new building and is being built out now. The center is called the Riordan McKenna Institute. It is located in Southlake, Texas, which is between Dallas and Ft. Worth, very near DFW airport.