Installment 10 - 10 Questions with Dr. Anthony Payne, PHD

[Technocracy]

1) I'm just wanting to know if there are any stem cell treatments available for someone who has Familial Polyposis (FAP). It's a rare genetic form of colon cancer.

Regrettably, none that I am aware of.



2) I was diagnosed with IPF (pulmonary fibrosis) in 1998, in 1999 I had cancer followed with chemo. I feel the chemo slowed down the lung deterioration, so therefore, I have survived longer than 80% with this disease. I am now looking at stem cell transplant. In theory which stem cell treatment would give me the best chance of success? Direct placement, bone marrow extraction? (This member is on O2 24/7 with low saturation and low diffusion, lung capacity is normal).

I assume you are asking about therapy for the IPF and not cancer (Albeit your statement and questions leave me wondering if you are looking for treatment for both). As you may already know from your own quest for answers, there is a body of published research indicating that bone marrow mesenchymal stem cells have a salutary impact on induced pulmonary fibrosis in animals. Many researchers and research-oriented clinicians feel that the same benefits are also conferred by umbilical cord blood-derived mesenchymal stem cells.

Now let me digress and point out something just for the record – just so you know: Not “all things stem cell” are necessarily good for you. How so? Well, a team of UCLA researchers led by Dr. Robert Strieter discovered that a particular adult stem cell in IPF patients travels to their lungs and produces collagen that contributes to scarring! (BTW, in a separate line of research, UCLA scientists found that Viagra® improves exercise capacity in IPF patients).

OK, so when it comes to IPF stem cells are a two-edged sword. A set of a patient’s own stem cells may contribute to evolution and progression of the disease, while it is possible others may help ameliorate it. Logic suggests that an ideal scenario is to suppress the adult stem cells that contribute to the problem, while concomitantly putting something in place that promotes healing. Or barring this, at least get some stem cells or other cells on-the-job whose activity will outstrip or otherwise undermine the disease process. The latter scenario appears more likely thanks to some enterprising Spanish researchers. Let me now spell this out for you:

First, I must set the stage with some background on the players involved in creating healthy alveoli:
Gas exchange develops in the lung thanks to a particular cell called the type I pneumocyst in the alveoli (Small air sacs in the lungs). Co-existing alongside the type I pneumocyst is the type II pneumocyst, which repairs and regenerates damaged or diseased alveolar tissue. In IPF, the repair and regenerative process is compromised as the disease progresses.
Enter the Spanish scientists -- researchers from the Biomedical Research Institute of Barcelona CSIC (IIBB-CSIC). What they did was induce an IPF-like condition in female rats, then transplant type II pneumocysts from male rats (using a minimally invasive intratracheal technique). The end result: The fibrotic alveoli in the rats with induced pulmonary fibrosis were regenerated!

A clinical study is to be launched at the Hospital Clinic de Barcelona involving six (6) recently diagnosed IPF patients who will be treated using the CSIC (patented) technique. If I were a betting man, I would wager this technique will produce some clinically significant results.
OK then, so maybe the Calvary is going to eventually arrive to save the day – the Spanish Calvary in this instance. What to do in the meantime, right? Wait? I would guess that if successful the CSIC will not wind up in FDA approved studies here before 2009 or 2010. If the outcome is good, FDA sanction of the technique for use in hospitals and clinics may not come before 2011. Given this, what should IPF patients do in the interim?
This brings me full circle to both bone marrow and cord blood derived mesenchymal stem cells. So far as I know, ...hypothetically, if you will....this is likely the best cell-based approach to ameliorating IPF available at this time. As such, you might want to research this further including soliciting input and guidance from a physician – hopefully someone knowledgeable in both pulmonary medicine and stem cell biology.

Also, click on this link For Those Considering Doing Stem Cell Therapy Abroad and read this particular medical consumer article I penned. It contains issues to bring up and questions to ask folks offering stem cell therapy abroad.


3) If we get the adult stem cells and they are removed from our bone marrow then put right back in without any altering, etc., will they be as potent as the ones that are altered through a laboratory?

The short & sweet is: It depends on what is done to the bone marrow that is harvested. If, for example, mesenchymal stem cells are extracted, cultured and expanded, this would likely be more efficacious for some conditions than merely re-infusing bone marrow. However, some of the compounds used in culturing bone marrow cells in most labs can (so to speak) embed in cell membranes or otherwise influence or alter the cells in ways that can have potentially dangerous consequences once the cells are infused or transplanted into the patient. While probably rare, cells so altered can evoke severe adverse reactions in patients. This is one of the reasons the FDA is adamant about having those who want to manipulate bone marrow do so under their watchful eye.

Just so you know: FDA regulations prohibit taking bone marrow extracted from a patient beyond “minimal manipulation” – essentially taking the marrow out and re-infusing it – in the absence of an IND (i.e., an FDA permit issued that authorizes specific research or to which OKs a treatment for administration on an emergency basis). As such, any clinic that removes bone marrow from a patient and then does anything that beyond “minimal manipulation” is technically guilty of violating FDA regulations and could be subject to prosecution.


4) I have been reading up on the different clinics and noticed that for example, a clinic in China uses anywhere from 4-7 transplants (one every week) versus other clinics that only use one total for the same ailment. I don't understand. Why this difference?

First off, you must take into account this: Most private, commercial stem cell operations abroad are (in my opinion) essentially carrying out largely unregulated human experiments. Many do so in the utter absence of regulations or accountability of the sort that prevails here in the USA (with respect to experimental medicine). This is good and bad in a way – good insofar as terminally and intractably ill folks who have no treatment recourse here in the States can try unapproved but promising treatments in a foreign setting (Treatments not likely to be tested out here for years to come) —bad in that when things go wrong or the treatment is bogus or even harmful there is often no legal or other recourse.

Now as these clinics and centers and such go about their work, some do so in a rigorous fashion – which is to say, they are systematic and scientifically methodical in devising treatments, administering them and carrying out pre- and post testing and then analysis of the results. Most (IMHO) do not (“Fill out these forms, wire your money, get treated and good-bye and good luck”). As these clinics gain insight from both published research (animal and human) and their own experience, many devise new treatment regimens and try them out. Some of these pan out for specific disease or conditions, many (maybe most) do not.

So, bottom line – what you likely see when it comes to the diverse and varied treatment schedules and regimens abroad is a reflection of experimentation in-progress informed by what their researchers (If they have any on-board, that is) and/or clinical staff gleam from the scientific literature and/or from the results, benefits, complications, odd occurrences, etc. that they see in treated patients.

This brings me to the example you cited: A clinic in China that does one (1) stem cell transplant per week over a four to seven week period vs. clinics that offer a single treatment. Is the Chinese approach better for condition x than the single dose treatment? This is very difficult to determine in the absence of well designed and executed studies. It is actually nearly impossible to compare outcomes – unless the cells administered are uniform in origin and nature (Say, a single cell line used to treat 2 groups with disease x – one on treatment schedule A, one on treatment schedule B). I am simplifying things way too much here – in hopes of communicating how difficult it is to access a given treatment in the absence of studies whose results are published in reputable journals (Why get published in a peer reviewed journal? Well, for one thing other researchers can try to replicate a given study, i.e., use the original study’s design, do their own study, and see if their results match up. If they do, this raises the bar of confidence in the given treatment or regimen. If the results do not line up, then something is amiss somewhere and its “drop back five and punt” time!)

Long story short: I cannot really tell you if regimen x for condition y is more effective than some other regimen – in the absence of valid scientific evidence.


5) Along the same lines as question number 4 - Why the difference in the amount of cells given also? The same ailment is treated so vastly different depending on the clinic. The cells could also be delivered sub-q or IV and yet it is for the same disease. As you are a theorist, what is the theory behind all this?

See my response to question 4 above.


6) In your article, "For Those Considering Doing Stem Cell Therapy Abroad", you mention that stem cells can't get past the blood brain barrier using IV method; that a better way would be catheter infusion or surgical implant. What is your recommendation for delivery for stroke-like brain injury? And why do some clinics still have success using IV or lumbar puncture?

What I said was, “Cells administered by IV would not, however, necessary breech the blood-brain barrier that keeps most chemicals with a molecular weight higher than 500 daltons out of the brain. One way to circumvent is to open up the BBB by use of a drug such as mannitol, which is what some stem cell clinics do. Another and most likely surer way to insure delivery of cells to the CNS is by direct catheter infusion or direct surgical implant.

The catheter infusion method typically involves introducing a catheter into the femoral artery in the leg and snaking it up through the circulatory system into the brain. Cells can also be implanted in the brain by stereotactic surgery, a process in which a patient’s head is locked in a special apparatus, very small holes are drilled in the patient’s skull very thin needles are scanner guided to target, and stem cells are injected. Cells can be introduced into certain spinal regions by direct surgical implant and intrathecal injection.”

Obviously an IV infusion of cells (with mannitol and such) and lumbar puncture are, as I indicated, two ways to get cells into the body and available to “do their thing”. However, when it some to stroke damage in the brain, I know of no compelling scientific evidence that an IV or lumbar puncture approach results in “success” (Which I take to mean substantive clinical improvements). There are many case histories posted on various stem cell clinic websites – patient testimonials – anecdotal evidence that suggests that these and other methods have improved the lot of some stroke patients. Maybe so, but scientifically rigorous evidence is, in my opinion, lacking.

One thing I have observed – which gels with animal studies – is that the window of opportunity for turning stroke damage around is narrow. If a stroke patient is treated with umbilical cord blood or bone marrow-derived stem cells within the first 3 days or so following his or her stroke, the odds of seeing substantial repair is perhaps greater than at any other time thereafter. BTW, some doctors argue that hyperbaric oxygen therapy administered within the same timeframe will have similar salutary effects.
I have also noted that, in general, the older the patient and the further out she or he is from their stroke, the less profound their response is to stem cell therapy (Whether cord blood or bone marrow or what-have-you). I say “in general” because there are exceptions (Once researchers can figure out why some folks respond so well why others do not, maybe they introduce the missing element or elements and thus transform a poor or non-responder into a good one).

Now if you asked me to just throw out an informed guess as what might prove the most effective stem cell approach for chronic stroke, I’d say direct implantation of neural progenitors created from induced pluripotent stem cells (iPS) [iPS are created from a patient’s own skin or liver cells or such. They thus have identical DNA to the donor/patient– which means no chance whatsoever of rejection. They will also have biologic activity that far surpasses neural progenitors derived from multipotent umbilical cord stem cells]. This is something going to debut in the not so distance future, thanks in part to a body of research taking place in a lab run by one of the world’s leading stem cell biologists here in the USA.



7) What are mesenchymal cells with CNTF? One of the doctors on the Pioneer forum believes that these cells would be best for stroke patients. Could you give us your opinion?

“Mesenchymal stem cells with CNTF”? This could mean one of two things: Mesenchymal stem cells infused, implanted or transplanted along with Ciliary Neurotrophic Growth Factor (CNTF) – or a mesenchymal cell genetically engineered to express or churn out CNGF.

With respect to what kind or type of stem cell might be most beneficial for chronic stroke, see the last paragraph of my response to question 6 above.


8) We are looking at therapy for our daughter who has CP. We have two concerns with the company we are considering. One is that it is a subcutaneous injection rather than IV and two that the vial is clear, like water. It seems a lot of medical professionals are saying that it can't have cells in it because if it did, it would be opaque. A "brain scientist" that I have been discussing this with agrees.

In my opinion, a subcutaneous approach does produce benefits in very young children – this is something I witnessed and helped document as part of a pilot study carried out in Mexico. Why? My guess – published as a hypothesis in the online journal Medical Hypotheses & Research –-- is that these cells cause fat cells to churn out Nerve Growth Factor which then travels through the blood brain barrier and encourages neurogenesis and such. This said, I believe that an IV approach is far superior, based on tracking children with CP treated with both methods from 2003 onwards (to 2007) and comparing responses. While not scientifically rigorous, I believe my observations will pan out once comparative, well designed and executed clinical studies are carried out.

Concerning the look of the material in the vial you saw: Let me answer your question with an actual incident. At the research institute where I work (Weller Health), we had our R & D lab analyze a vial said to contain 1.8 million cord blood stem cells, but which was as clear as water. The vial did contain cells – actually a mix of cord blood-derived cells – about 10,000 being actual stem cells -- with the total tally being 400,000 cells (Both blood-derived non-stem cell and the 10,000 stem cells). Our chief scientist, who is actually regarded as one of the world’s leading stem cell biologists by men such as Dr. Hans Kierstead, told me that if the vial had contained 1.8 million cells – it would have been opaque and not clear. This gels with what stem cell experts have reported (Print media and news reports).


9) If I am going to get autologous stem cell treatment, why shop around when these are my own cells? The prices are all over the board and most sound like they are using the same methods, so what could possibly make one worth more than the other since I am the one providing the most vital ingredient?

Autologous stem cells offer many biologic advantages including preclusion of rejection. This said, most are as age-effected as the other tissues in your body. What would be ideal would be to use cells that are unaffected by age – spermatogonial or sperm precursor cells, for example – turn them into pluripotent cells – differentiate them into the cell type needed such as neurons or heart cells – and implant or transplant them. This, by the way, is an approach actually pioneered by the head of our R & D lab at Weller Health Institute. I am told it is likely to become available for experimental use around 2010 or into 2011.


10) Can you tell us just what a biological theoretician does, please?

As a theoretician I create testable hypotheses and ideas which bench or clinical researchers can then formally evaluate via lab experiments and/or clinical studies. I also concoct inventions and approaches geared to “advance the human condition” – a lofty phrase which essentially means coming up with ways to make life easier or healthier or in some other way enhanced in terms of quality or substance.
You find some of my hypotheses – some published in peer reviewed journals – some not – on Healing Care for You

[Technocracy]

An update from Dr. Payne.....


Q6 – paragraph 5:
iPS are created from a patient’s own skin or liver cells or such. They thus have identical DNA to the donor/patient– which means no chance whatsoever of rejection. They will also have biologic activity that far surpasses neural progenitors derived from multipotent umbilical cord stem cells]. This is something going to debut in the not so distance future, thanks in part to a body of research taking place in a lab run by one of the world’s leading stem cell biologists here in the USA.

Clarification:
The iPS technique that has been developed – by the head of the R & D lab at the institute (Weller) I serve as a theorist and senior science writer—does NOT involve use of viruses to create pluripotent stem cells. Bottom line: A few hundred liver cells would be transformed into stem cells that demonstrate pluripotency characteristics associated with embryonic stem cells, but without the risk of giving rise to cancer.
Dr. Anthony G. Payne