Full title: Safety Analysis of Autologous Stem Cell Therapy in a Variety of Degenerative Diseases and Injuries Using the Stromal Vascular Fraction
I was glad to see stem cell therapy and PRP injections getting some love from the mainstream media recently - courtesy of AARP, There was an article in AARP The Magazine from May, 2014, titled "Arthritis:4 Treatments to Try Now", in which the author recommends injections to help with symptoms of osteoarthritis.
Osteoarthritis is the most common form of arthritis, essentially wear and tear on the joints. Over time, the protective cartilage wears down, eventually leading to pain as the bones rub against each other. There are few treatment choices, most of which can have detrimental side effects. Anti-inflammatory medications, or NSAID's (such as ibuprofen and naproxen), can be used to help with the pain, but their use for extended periods can be dangerous for multiple reasons. [I plan to devote an entry on this exact topic at www.ColoradoOnTheMend.blogspot.com soon.] Exercise and physical therapy can also help, but their effectiveness may be diminished due to pain interfering with a patient's ability to proceed long-term. And finally, there is the prospect of surgery - either in an attempt to repair damaged cartilage or with joint replacement. Again, there are serious side effects and potential life-threatening complications with surgery, and there is no guarantee it will work.
That is why PRP and stem cells show such promise - few side effects and a great potential upside. The author mentions a great article from January, 2014, in the Journal of Bone and Joint Surgery titled "Adult Human Mesenchymal Stem Cells Delivered via Intra-Articular Injection to the Knee Following Partial Medial Meniscectomy", wherein patients who received stem cells had increased meniscus volume and a significant reduction in pain compared to the control group. Here is the direct link to that study - http://jbjs.org/content/96/2/90 . Again, we have seen these results with our own patients, and continue to find ways to improve outcomes even more.
The AARP article also mentions newer medications, knee distraction (a procedure involving an external metal frame applied around the joint; the frame must be in place for months, with extensive rehab involved), and cartilage replacement as other therapies to try.
Here is the link to the article - http://www.aarp.org/health/conditions-treatments/info-2014/arthritis-treatments-to-try-now.html
This is part 2 involving the potential dangers of antiperspirants. Again, the main culprit appears to be aluminum, although parabens (commonly found in deodorants) have also been found to play a possible role in breast cancer. Parabens are synthetic antimicrobial preservatives used in a wide array of cosmetics and even as food additives.
An article in the European Journal of Cancer Prevention by Kris McGrath in 2003 ("An Earlier Age of Breast Cancer Diagnosis Related to More Frequent Use of Antiperspirants/Deodorants and Underarm Shaving": 479-85) studied age at time of breast cancer diagnosis in relation to how long the patient had been shaving and using antiperspirants/deodorants. As stated in the journal, "in conclusion, underarm shaving with antiperspirant/deodorant use may play a role in breast cancer. It is not clear which of these components are involved. Reviewed literature insinuates absorption of aluminium salts facilitated by dermal barrier disruption."
Again, no true causal link could be definitively established, but the end conclusion is that there is most likely some nexus between breast cancer and use of antiperspirants/deodorants and underarm shaving. The role of shaving in this process is that it alters the normal barrier of the skin, possibly making absorption of aluminum and/or parabens easier or greater than normal.
Philippa Darbre also more recently published an article in the same journal that shows experimental links, stating "evidence shows that at these tissue concentrations, aluminium has the potential to adversely influence breast epithelial cells and the breast microenvironment leading to alterations associated with carcinogenesis, progression and metastasis" ("Aluminum and breast cancer: Sources of exposure, tissue measurements and mechanics of toxicological actions on breast biology." European Journal of Cancer Prevention (Nov. 2013): 257-61; http://www.ncbi.nlm.nih.gov/pubmed/ 23899626).
This same researcher also published an article years earlier that stated "the strongest supporting evidence comes from unexplained clinical observations showing a disproportionately high incidence of breast cancer in the upper outer quadrant of the breast, just the local area to which these cosmetics are applied. A biological basis for breast carcinogenesis could result from the ability of the various constituent chemicals to bind to DNA and to promote growth of the damaged cells" (Darbre, P. "Underarm cosmetics and breast cancer." Journal of Applied Toxicology 23, No. 2 (2003): 89-95; http://www.ncbi.nlm.nih.gov/pubmed/12666152).
An author I mentioned previously in regards to his research on aluminum and Alzheimer's Disease has also extensively studied aluminum and breast cancer. In 2007, Christopher Exley published a study titled "Aluminum in human breast tissue", finding confirmation of "the presence of aluminium in breast tissue and its possible regional distribution within the breast. Higher content of aluminium in the outer breast might be explained by this region’s closer proximity to the underarm where the highest density of application of antiperspirant could be assumed." He notes that the upper outer quadrant, the breast area closest to the underarm, consistently showed higher aluminum levels than other quadrants. Although this does not prove that aluminum is the cause, it should make us all think more about our exposures. This study goes on to say that "aluminium is a metalloestrogen, it is genotoxic, is bound by DNA and has been shown to be carcinogenic. It is also a pro-oxidant and this unusual property might provide a mechanistic basis for any putative carcinogenicity. The confirmed presence of aluminium in breast tissue biopsies highlights its potential as a possible factor in the aetiology of breast cancer” (Journal of Inorganic Biochemistry 101(9) (2007): 1344-6; http://www.ncbi.nlm.nih.gov/pubmed/17629949).
Some of these same authors have looked at the effects of parabens as well - Darbre published an article called "Concentrations of Parabens in Human Beast Tumours" in which she notes that parabens can bind to estrogen receptors and can effectively increase the growth of MCF7 human breast cancer cells (Journal of Applied Toxicology 24 (2004): 5-13; http://www.ncbi.nlm.nih.gov/pubmed/14745841). Here are links to related articles:
- http://www.ncbi.nlm.nih.gov/pubmed/12975767
- http://www.ncbi.nlm.nih.gov/pubmed/18484575
- http://europepmc.org/abstract/MED/21155623
Again, I am in no way implying that there is data supporting a direct link between breast cancer (and Alzheimer's) and aluminum from antiperspirants. What I am trying to show is that there is growing evidence suggesting a link. My thinking is that even a potential cause and effect relationship is worth being aware of, and possibly worth taking action against. In the next blog entry I will conclude with some of those actions that are worth investigating.
When it comes to the debate over antiperspirants/deodorants, the jury is still out. I have mentioned a variety of studies that tend to point towards a link between aluminum and both breast cancer and Alzheimer's Disease. However, there are other studies that show no link. That is the frustrating part - there is no consensus. However, my belief is that just because it hasn't been proven to cause harm does not mean it is truly safe or inconsequential. That is where we must each make a choice based on the evidence that we do have, and by using logic and reason. There is enough information on this subject to make me doubt the safety of aluminum and parabens.
So what are the options in terms of dealing with underarm sweat? Well, if you sweat only mildly, maybe you just avoid products with aluminum and parabens. If you experience moderate to excessive sweating, there are many options, although not necessarily many good options. If you eliminate antiperspirants from the equation, you are left with the following: no treatment (meaning you use nothing, other than paraben-free deodorants to try to mask odor, but doing nothing to treat actual sweating); Botox, to temporarily stop sweating (this treatment can last between 2 and 8 months, although I have had patients who tried this and felt it did not help at all, and I have seen patients whose sweating was worse after the Botox wore off); medications, such as a class of drugs called anticholinergics (these have never been directly studied for hyperhidrosis/excessive underarm sweating, nor have they been FDA approved for this use - plus they have a range of unpleasant side effects including dry mouth, constipation, blurry vision); for more severe sweating problems there are surgical options, including local underarm surgery (liposuction, curettage, and laser techniques - these have potential surgical complications, and outcomes that vary widely) and more invasive surgery such as endoscopic thoracic sympathectomy, wherein the nerve pathways inside the chest wall are cut to disrupt the passage of signals that lead to sweating (this is a permanent surgery that is risky and often leads to increased sweating in other parts of the body); and finally iontophoresis, using devices that produce a mild electrical current to inhibit sweat glands (this is a process that initially requires treatment every couple of days for 10 sessions, then maintenance once every week or two).
In addition, the newest treatment is something called miraDry, using microwaves to eliminate sweat glands and provide a long-lasting treatment. We have been performing this procedure for over 2 years with great success. Patients who have had 2 treatments tend to have an average of about 85% reduction in their underarm sweating, per the company's FDA trial, and we have seen similar results within our practice. For more info, go to www.miradry.com . Also, check out our website at www.gomend.com . This is a therapy that offers a lasting result with little to no down time and few transient side effects. I am a fan, as I personally underwent the procedure and can vouch for its efficacy. I have been thrilled with the huge reduction in my underarm sweat, plus I no longer have to use antiperspirants every day! Feel free to ask me any questions, as I am both a patient and a provider.
A recent study from Laura Shin and Daniel Peterson in Stem Cells Translational Medicine (2013; 2:33-42) attempts to clarify exactly how stem cells given as a treatment actually induce healing. The conventional theory has been that these cells act by differentiating once inside the body, as in they change into the cell types that the body needs to repair and heal itself. This equates to the analogy that they act as seeds that then grow into the new tissue.
However, this recent study seems to point to a different mechanism of action.The researchers used human mesenchymal stem cells in mice that were given excisional wounds that were splinted open. The splint wound model more closely duplicates how human wounds heal by granulation and re-epithelialization (rather than by skin contraction, the normal repair mechanism in rodents). The treated mice were given a pair of these wounds, one that received an engraftment of stem cells and the other left untreated. The stem cells were genetically modified so the researchers could trace the cells after giving them to the mice. There was also a control group who had similar paired wounds, but received no stem cells.
The results of this study showed that the animals that received stem cell therapy had accelerated healing when compared to the control group. However, the stem cells themselves did not seem to be the cells directly involved in the wound repair. The traced stem cells were abundantly evident in the treated wound just one day after delivery, but the numbers were dramatically reduced by day 5, and these cells were not even detectable in the wound bed by day 10.
The wounds that received no stem cells showed a rather significant delay in closure compared to those receiving stem cells. The stem cells were also only engrafted into one of the paired wounds on each treated mouse, but the non-treated wound on that mouse showed a moderate improvement in healing over the non-stem cell mice as well.
The results seem to indicate that the improved closure of the wounds despite the relatively rapid decrease in engrafted stem cell numbers may be due to signalling within the wound bed that helps to modulate and direct the host's own cells. The injected stem cells appear to recruit the patient's own stem cells to the area of injury, both at the engrafted site as well as distant sites in the body to some degree. These signals also seem to be maintained after the engrafted stem cells are gone. Thus the authors propose that while the stem cells are useful for healing, it is the subsequent healing response that they induce that ultimately leads to wound repair. If this is truly the manner that stem cells are involved in the healing process, it is the signals they produce that are the key to success with future therapies.
This entry is in regards to an interesting review article in the October, 2013 Stem Cells journal, by Darwin J. Prockop, M.D., Ph.D from Texas A&M University. He writes about two specific negative feedback loops that stem cells introduce into generic pathways of inflammation.
(I apologize about the technical aspect of this blog entry, but I found it difficult to put a lot of the medical terminology into layperson terms.)
The first feedback loop is brought about by pro-inflammatory mediators from certain sensor cells that activate stem cells and upregulate the expression of COX2 and other parts of the arachidonic acid pathway. This then causes the stem cells to secrete more prostaglandin E2 (PGE2) which then appears to cause pro-inflammatory macrophages to instead secrete anti-inflammatory mediators (including interleukin-10 and interleukin-1).
The second negative feedback loop also involves stem cell activation from mediators. This activation causes stem cells to increase the expression of certain genes, specifically the anti-inflammatory protein TNF-alpha stimulated gene/protein 6 (TSG-6). This results in a decrease in TNF-alpha and other mediators that stimulate inflammation.
These two loops provide evidence that stem cells have a definite effect in decreasing inflammation, a finding that once again shows promise for stem cells as a treatment modality.
The lab testing evidence for these two loops was developed primarily in experiments wherein the stem cells were given after an acute tissue injury that induced the inflammatory response. The author notes that further investigation is needed to determine if these feedback loops exist in situations such as mild inflammation or unresolved inflammation due to a chronic disease process. It is also intriguing to note if these negative feedback loops would exist in all patients, or if genetic differences would influence them.
These negative feedback loops are only one portion of the role that stem cells have in the healing response. There are many other factors involved, including stimulation of growth factors, increased vascularization, recruitment of more host stem cells, modulation of the immune response, reduction of reactive oxygen species, transdifferentiation of cell types, and increased paracrine signaling, among many other methods.