View Full Version : Installment 62 - Ask the Doctor with Ricardo Luis Rodriguez MD

09-02-2013, 04:36 PM
About Ricardo Luis Rodriguez MD

Dr. Rodriguez is a Board Certified Plastic Surgeon with 25 years experience, having both academic and clinical practice interests. Academic interests include stem cell research and fat graft technical development. He has ongoing development relationships with several Biotech companies.
His clinical practice is in Baltimore, Maryland. It encompasses the spectrum of cosmetic and esthetic Plastic Surgery.
A significant proportion of his practice is from out of town and he has operated on patients from as far afield as Europe and Asia.
In June, 2013, His appointment of faculty as a member of the University of Maryland School of Medicine Center for Stem Cell Biology & Regenerative Medicine recognizes a level of excellence in and dedication to stem cell research, relevant patient care, education, and/or community outreach activities.
The mission of the University of Maryland School of Medicine Center for Stem Cell Biology & Regenerative Medicine is to encourage collaboration in stem cell research among faculty members across the University of Maryland System and beyond. The Stem Cell Center will foster synergistic biomedical interactions in Maryland between public and private institutions using all kinds of stem cells, various species models and basic and translational research to enhance the diagnosis, treatment, and prevention of multiple human diseases. The Center will cultivate a broad range of interdisciplinary research in a highly collaborative environment while encouraging the translation of these discoveries into new commercial products to maximize the impact on human health and disease.
Dr. Rodriguez is a Clinical Instructor of Surgery at Johns Hopkins Medicine in Baltimore, MD. He participates in lectures to Resident Physicians.
He has a research affiliation with Dept. of Radiology (MRI cell Imaging). Residents in training for Plastic Surgery Johns Hopkins Dept. of Surgery will start operating in his Surgicenter this year.

Dr. Rodriguez is President of ICMS
Ricardo Luis Rodriguez MD
(office)410 494-8100

Q & A

Q: I have read about a person's own stem cells being placed into a transplanted organ in the hopes of preventing rejection and the possibility of not needing to take anti-rejection drugs. Has this procedure been performed during transplants at your hospital? If not, are their plans to do so?
A: This is a complex question. I'll start with the basics.
First- Stem Cells do not express the cell surface markers that tag them as "foreign". For that reason, you can inject them into another person and they will likely not get rejected (at least immediately). The prevailing evidence is that over time the stem cells disappear in their new host, although they do influence the behavior of the host tissues beyond the time they are detectable. Thus they seem to reprogram the behavior of key populations of host cells.
Second- Stem cells can blunt the immune response. For example, in Graft versus host disease, a bone marrow transplant is done and the transplanted cells attack the recipient because they see it as "foreign". Stem cells have been used in this case to blunt the immune response of the transplanted cells. In this case, the timing is important. If you give the stem cells at the same time as the transplant, the results are not great. If you give the stem cells after the transplant, when the immune attack is beginning, the results are much better.
Finally- At Johns Hopkins, where they are doing whole limb transplants, what they have discovered is that the stem cells present in the donor bone marrow do seem to blunt the immune response so that the dosage and timing of immune suppression medications can be reduced. This raises the possibility that transplanting organs WITH donor stem cells may reduce the need for immune suppressive therapy, but much research still needs to be done.

Q: US based researchers from Wake Forest School of Medicine and Saint Louis University looked at a disintegrin and metalloprotease (ADAM)gene known as ADAM33 in 880 long-term heavy smokers. Located on chromosome 20, ADAM33 has been linked with asthma in previous studies. This new study is unique in comparing long term smokers with COPD versus a control group of long term smokers without COPD. The research found 5 single nucleotide polymorphisms (SNPs) - human DNA sequence variations in ADAM33 that were more frequent in the COPD group than in the group of smokers without COPD. One SNP, known as S1, had a particularly strong link to lung abnormalities. "Functional studies will be needed to evaluate the biologic significance of these polymorphisms in the pathogenesis of COPD," according to the authors.
My question: If this defective gene is still defective after stem cell treatment then wouldn't stem cell treatment have to be combined with gene therapy for effective correction?
A: When a researcher says "functional studies will be needed to evaluate the biologic significance", what it means in plain English is "we have no clue if this means anything in real life". It is a just finding, and research is full of findings that turn out to be red herrings or blind alleys.
What I'm beginning to think about most chronic diseases is that they represent final common pathways of the body reacting to a certain stimulus. In the example of COPD, there are many causes but one final common pathway- destruction of pulmonary alveoli. Thus, if we can affect the body's response to the different stimuli, the pathway can be aborted.
In this particular case, one would have to ask if the behavior of the patient's own stem cells would be affected by this mutation. If it was, then autologous therapy would be questionable. Perhaps allogenic (from a different donor) would be preferred because these cells would not have the genetic defect.
As far as genetic therapy, the downstream effects of changing even SNP's is so unpredictable that years of research would be needed just to answer what these SNP's do before deploying genetic therapy in humans.

Q: I am 42 years old and have the diagnosis of Facioscapulohumeral muscular dystrophy. In 2008, the disease progressed with my right foot dropping. From that date to now, I use an AFO in my right leg. I am very independent and active and walk without assistance, but this is a progressive disease and I would like to know:

Do you provide or know of stem cell treatment for patients with the same diagnosis as mine? If so, what has been the outcome in general?
Is there a specific stem cell therapy recommended? Please elaborate on details of the treatment and protocols if you have knowledge in this area. I am interested in knowing how the cells are collected, manipulated, method of delivery and post treatment.
We all hear that other countries are more advanced than the USA in stem cells. If treatment for my condition is not available in the US would you know of offshore clinics treating it that are reputable?

A: Your questions are very specific, and unfortunately I don't have specific answers for you.
The way stem cell therapy works in the US is that a trial is organized for stem cell therapy to treat a specific disease. If you want to know if a specific trial is recruiting patients for your particular condition go to http://www.clinical trials.gov and search for your particular condition. It is very hard to start a trial in the US and a lot of money is required so consequently very little stem cell activity is going in the US. We are ahead of everybody else in knowledge, facilities, and expertise, but not where it matters- implementation. This is because of the regulatory burden.
As for specific stem cell therapy, I can only offer general guidelines.

Your condition is systemic, therefore Intravenous delivery that delivers a systemic dose is preferred to injections at local sites.
Although there is no formal consensus, you will need a dose of at least 1.5 million cells per Kilogram of body weight. This means most probably cultured cells.
Autologous (using your own stem cells) is always preferable to allogenic or embryonic cells for a multitude of reasons. This means that you will donate tissue then wait for a couple of weeks while the cells are being cultured.
There are many offshore clinics doing stem cell therapy, but the problem is there are no formal accreditation bodies that are creating standards for accreditation. These would ensure that the clinics are processing tissue and delivering care in a proper way.

The ICMS is currently working with the AABB (American Association of Blood Banks) to develop such standards. We feel it is of extreme importance to patients like you and the many others that want therapy but are vulnerable to unscrupulous therapists.

Q: What are the risks to my health with autologous stem cell treatment? Are there adverse side effects? I've read that cells can morph into cancer cells. I had breast cancer, stage 1 and am a cancer survivor since 2000. I had a mastectomy and light chemo.
A: There is very little risk to autologous stem cell therapy in general.
Embryonic stem cells, Induced Pluripotential Stem Cells, and Stem Cells that have been cultured for a long time (over 30 cell cycles) can develop tumors, but so far autologous Stem Cells that have not undergone repeated cell cycle divisions have proven very safe.
As to your particular case, cancer survivors, there is a fly in the ointment. It is the issue of whether there is stem cell interaction in the tumor microenvironment that leads to tumor growth. There is enough contradictory evidence to give one pause. Granted, in your case the 13 year gap is very reassuring, but I would get a metastatic tumor work-up to make sure there is no evidence of disease before proceeding with your therapy.
We are presently about to initiate a clinical trial injecting Stromal Vascular Fraction cells into breast cancer survivors who have had irradiation to the breast. They will be labelled so that they can be tracked by MRI. In this case we should be able to see if the cells are attracted to a particular spot, which would make one suspicious. We do not expect this, rather we expect the cells to spread evenly through the irradiated tissue.

Q: Can you give me an update on the collaboration between ICMS and AABB to establish standards for stem cell therapy?
A: We just met last week with the AABB. They have a new CEO who is very motivated to proceed, but the terms of the agreement are being redefined. We project the new standards to put out for public comment in 12-18 months. We have gone through one revision so far, and the work can be slow and methodical, but with the recent publication of the 6th edition of the AABB Standards for Cellular therapy we expect to leverage those efforts to accelerate our own.

Q: I have had expanded autologous stem cell therapy for progressive MS with great results. The FDA says the doctor was producing a drug. If the Regenerative Sciences vs FDA case is successful in October than a doctor can once again produce cultured cells in his office and give them to his patient. But what about cell banks like Celltex that want to culture expanded cells for a patient, and give them back to the doctor to administer? Would this still be FDA regulated as the production and distribution of a biologic to physicians?
A: We have no idea what the courts will say. A very good friend of mine who is a tenured Professor at Boston College Law School (Prof. Mary Chirba, MPH, PhD) and follows these matters closely predicts the courts will uphold the FDA position. She has been right on the money on all these legal developments so far so I see no reason to doubt her.
As for Celltex, there are multiple reasons why they ran afoul of the FDA, but suffice it to say that any culture expansion of cells in any way shape or form is viewed as production and distribution of a biologic by the FDA, even if it is your own cells.

Q: I have CIDP. since January 2011. I took ivig+plasmapheresis+prednisolone but my doctor said my inflammation is strong. Its turned to severe secondary axonal in November 2012. I walk with a walker. I take IVIG 1gm/kg every 2 weeks. I think the inflammation is stronger than ivig. I heard about stem cells. Which is better for me - bone marrow, cord, embryonic, mesenchymal? Do I have to take a high dose of chemotherapy with stem cells to get the inflammation under control with medication or is there anything else that might help?
A: I assume you mean Chronic Inflammatory Poly Demyelinating Neuropathy. We have no idea whether stem cells would work, but if we take the position that it is an inflammatory condition, and we take the position that Stem Cells are immune modulatory, then we could postulate that stem cells would work. But that is just a theory. One would have to have a clinical trial to see if it works.
On the other hand, as an informed patient you should have the right to try any therapy as long as you accept the risks and understand the uncertainty of outcome.
As to which type would be better for you, as I have stated above my bias is towards autologous (your own cells) stem cell therapy. I also favor adipose (fat tissue) derived stem cells because they are abundant, easily accessible, and can be cultured to therapeutic quantities in a shorter time than bone marrow.

Q: If all patient activists' efforts fail, do you see any way to encourage physicians to treat patients via the FDA's expanded access program?
A: I frankly do not see how the FDA's expanded access can be of help to significant numbers of patients. It is a procedure that involves FDA approval and that is never a speedy process. Secondly, by definition it is for "serious or immediately life-threatening" conditions that have no other therapeutic alternatives. Thus if a chronic condition has other alternative therapies it will be very hard to qualify for expanded access.

Q: Over one third of those with COPD have colonization of their lung tissue with a common pathogen according to a research study. The pathogen Pneumocystis was found in the lung tissue of smokers with COPD. Pneumocystis is a bacterium that causes pneumonia in those with weakened immunity. In this study 68 smokers with COPD of varying severity undergoing lung surgery or lung transplantation were compared with 44 patients receiving a transplant for other reasons. Lung tissue analysis showed how 37 percent of the 30 smokers with severe COPD had colonizstion with Pnemoncystis, compared to 5.3 percent of the smokers with less severe COPD. In the control group, the colonization rate was 9.1 percent. It looks as if Pneumocystis might be a factor in the progression of COPD. My question is that if a COPD patient tests positive for this pathogen, would a regimen of antibiotics slow progression? If a person has the pathogen would stem cell therapy not be as effective?
A: Refer to the second question above. This is another case of the myriad possible contributory factors to COPD. As I said before, if we approach the problem of COPD in the light of "final common pathway", the fact that there is Pneumocystis is not as important as the reaction the body has to it.
Antibiotics in the early stages of Pneumocystis carinii infection may be effective in preventing COPD in those cases of Pneumocystis, but Pneumocystis is not a common cause of COPD and is most often seen in immune compromised patients such as HIV.
Our bodies have many bacteria and viruses peacefully coexisting which become "pathogenic" when systemic alterations occur. Examples of this are immune compromise from disease or immune suppressive therapy, and even the use of powerful antibiotics that suppress natural competitors and favor the rise of "pathogens".

Q: Can you tell us about your work which was awarded a grant in 2013 by the Maryland Stem Cell Research Fund?
A: The specific grant is to label Stromal Vascular Fraction Cells with a Fluorocarbon compound that enables us to track the cells in the human body after injection. We track them using MRI, which allows us not only to see where the cells go, but how many cells there are.
Stromal Vascular Cells is a collection of cells obtained by digesting tissue with collagenase. The cells are a mixture of stem cels, precursor cells (Less "stem like" but still not fully differentiated), immune effector cells such as macrophages and lymphocytes, and stem cells proper. The percentage of stem cells in SVF has been quoted as anywhere from 5-20%. The theory is that SVF works more by cell communication and reprogramming rather than by stem cells differentiating into tissue types. The advantage of SVF is that one can get a therapeutic dose of cells in a single operative session.
Although in principle the technology could be used for any condition, the specific protocol we are using is on patients who have had Breast Cancer and have been treated with surgery and radiation.
Stem Cells are the only thing that work well to heal radiation damaged tissue so we are very excited about this trial. There are millions of patients who have painful and disabling after effects from radiation therapy and they have nowhere to turn as nothing else seems to work.
Likewise we are very excited about the possibility of tracking cells in patients as this technology could be used for many conditions.

Q: What is your personal opinion - Should physicians be allowed to treat their patients with expanded MSC therapy or should the FDA ruling be followed which would require years of being trialed as an Investigational New Drug before patients can have it in the U.S.?
A: Personal opinions are not worth much. In the end what counts are facts. I want to generate facts with my trials. One of the reasons I'm excited about SVF is that it is not expanded cells so it avoids many issues with the FDA and I am guessing that the FDA will ultimately look at the evidence and realize that SVF has a different risk profile. So I have short term goals and long term goals.
In the short term, SVF can be done safely with low complexity. For example, I'm working with a company named GID to develop a simple reliable method to get high yield of SVF in a sterile manner that can be done in a regular operating room with minimal training. That can be done now safely even if outside the US.
The problem with autologous stem cell culture expansion is that it is technologically very complex. So it may be safe when done right, but the problem so far is that so few people do it right. That is why you get the occasional horror stories. Frequently the problem is not the stem cells themselves but some other snafu in the procurement and delivery of the stem cells. We have seen improper evaluation of patients, deplorable lab methods, lack of quality control, etc.
For the long term I am involved with the AABB so we can publish standards and guidelines that will lift the quality of the produces in general. Having said all that, here is my opinion:
The FDA will not reverse itself. The technology will be developed in the US by people like me but deployed outside of the US. It will become a lot safer and predictable when standards and guidelines generated in the US are adopted by clinics outside the US. Patients will be able to pick the best clinics by virtue going to clinics that have gone through an accreditation process. Once there is a critical volume of patients going out of the US political pressure will rise to the point that there will be a legislative, not regulatory solution.

Q: Is there any historical analogy we can look to of an innovative therapy that has such good results that physicians started using it before the research caught up to explain why it works?
A: Most of the medications and surgical procedures we use today were adopted before we fully understood how they work. The belief that we must fully understand how something works and that everything has to be risk free is a recent attitude in or society.
Ironically, with stem cells a lot of work has been done to understand how things work, so it is not like we are proposing to use stem cells because they are "miracle cells". For example, in my specific case (using stem cells to combat radiation damage) there is a significant amount of knowledge about cytokine cascades, the role of TGF-Beta and Hepatocyte Growth Factor to explain how stem cells reverse radiation damage. Likewise, many pathways of the immune modulatory effects of stem cells have been mapped out to a very specific degree. So there is a lot of knowledge already about Stem Cells to go forward in a knowledgeable and thoughtful way.
Ultimately, the problem with progress in the stem cell field and medicine in general in the US is reflective of a wider conflict in society- the balancing of risk and benefit. Our society is defaulting on the side of safety. We have to become comfortable with the possibility that unusual benefits carry risk. The problem is that the safety default has stripped the patient of choice. And that is a big problem for the advancement of medicine.

Q: Inspired by your interview with Mary Ann Chirba, patient activists have attempted to express our concerns about the FDA's 2006 ruling in 21 C.F.R. 1271.3(d) that classified our stem cells as drugs. Can you comment on these efforts (see links below) and suggest any direction for the future?
A: All of us have a different role to play. I can do the science and push the science forward. But I am viewed as an interested party.
Anyone of you who reads this blog has a tremendous amount of power because you are a Constituent and you have a vote. Get involved, write to your congressman, talk to your friends, get them riled up. Use social media. If everyone of you posts about these links and issues in Facebook, Linkedin, etc, it is what's called a force multiplier. Nobody else is going to do it for you.

Sick patients want to sue the FDA over denial of access to our own stem cells for life saving therapies.


Finally, thank you for inviting me to this forum. I will be happy to contribute again at a future date.