PRP and Hair Regrowth

Platelet-rich plasma (PRP) has been shown to be an effective treatment for hair loss.  I have only performed this procedure on one patient thus far, using PRP injections in conjunction with micro-needling.  This patient had some success after two treatments, and will be returning for a third session in the future.

Androgenic alopecia , or male pattern hair loss, can affect up to 80% of white men and even up to 40% of women.  There are multiple treatments available for this type of hair loss, although some of them will offer no benefit to many people.  Minoxidil and finasteride are two of the more common drug therapies approved by the FDA. In general, finasteride will help you keep the hair you have while minoxidil has some potential to grow new hair. Laser light therapy is another option, although it appears this may help keep the hair you have but will not actually grow new hair; it also seems to be the least effective of the therapies. One of the more successful therapies is hair transplant surgery, although the success rates vary widely and this can often necessitate more than one treatment.

A recent article published in the November 2015 journal Stem Cells Translational Medicine focused on the use of PRP injections in the realm of androgenic alopecia.  The research by Gentile, et al., titled "The Effect of Platelet-Rich Plasma in Hair Regrowth: A Randomized Placebo-Controlled Trial", studied the effect of PRP after 3 treatment cycles that were 30 days apart.  There were 23 study participants.

The procedure used in this study was simply PRP injected into an area of the scalp containing hair follicles, along with placebo injections in order to truly evaluate the effects. No local anesthesia was used during these treatments. The results were evaluated in 6 separate stages: at the beginning of the study, then at 2 months, 6 months, 12 months, 16 months, and 24 months.  These evaluations were made via photography, physician and patient assessments, and biopsies.

The results were very promising across the board. There was a significant increase in the overall hair count in the PRP treatment area after 3 months; the PRP area had 33.6 more hairs on average while the placebo region had 3.2 less hairs on average.The average density on hairs increased in the PRP treatment region by 45.9 hairs per square cm, with a 3.8 hair per square cm loss in the control area.  Biopsies showed an increase in epidermal skin thickness and an increase in the overall number of hair follicles in those areas treated with PRP.  Those are all very promising results from a procedure with low relative risk.

At 16 months, 4 of the 23 study patients showed some degree of progressive hair loss again.  These patients were re-treated with a series of 3 PRP treatments; the results after those injections were not evaluated in this study.

This is yet another in a series of small trials studying the efficacy of PRP for treatment of hair loss. Other studies have shown similar promising results.

Here is a photo from the article referenced.  This is a 29 year-old male 2 weeks after the final treatment, with both increased hair density and total hair count.

The method I have used has 2 potential ways to stimulate hair growth.  The first is the injection of PRP as proposed in this research study and others like it.  The other mode to potentially promote hair growth is the use of microneedling.  This is a technique whereby a number of fine surgical grade microneedles are used to stimulate dermal stem cells and activate growth factors in the scalp. There have been studies also showing the effectiveness of microneedling for hair loss, and I will look at some of those results in the future.

Stem Cells and Myopia

An interesting review article in the July 2015 issue of Stem Cells looks at using stem cell therapy to prevent the progression of myopia ("Concise Review: Using Stem Cells to Prevent the Progression of Myopia - A Concept", by M. Janowski, et. al.).  The authors, a team from Johns Hopkins University School of Medicine, discuss the prevalence of myopia and how different mechanisms might be amenable for stem cell treatments.
 

Myopia, or nearsightedness, is basically the condition where objects that are near are seen clearly while far objects are blurry.  There are a couple of causes, either the eyeball being too long or the cornea being overly curved. Both scenarios cause light entering the eye to not focus appropriately.  This leads to the blurred vision of distant objects.
 

This condition is rather common, affecting about 30% of the population in the US. However, it is becoming an increasingly more common disorder throughout the world. There are both hereditary and environmental influences that lead to the condition, and as the world becomes more industrialized the environmental effect is increasing. It seems that this is due to strain on the eyes caused by educational stressors along with a decrease in sunlight exposure. In areas of the world with minimal education, the incidence is rather low; however, in those regions with more advanced educational systems the rate of myopia is rapidly increasing, possibly towards pandemic levels.


The authors propose a couple of ways in which stem cells might be useful in treatment of myopia and its progression. The first is in use of stem cells to support the sclera of the eye, as the myopic sclera is commonly characterized as being weak, thinned, and less rigid than normal. This theory is based on applying stem cells to an area in the back of the eye in a region known as the subscleral space, between the sclera and the choroid. These cells would then differentiate into fibroblasts that can produce extracellular matrix, strengthen and reinforce the sclera itself, and prevent elongation of the eyeball. In this case, the stem cells have a direct effect on the eye.



The second proposed method of treatment with stem cells is in the area of dopaminergic signaling. Dopamine is a neurotransmitter, a type of chemical produced by certain cells to send signals to other cells. There is significant cross-talk between the sclera and the retina, and a proposed cause of myopia is a disruption or dysfunction in that signaling process.  Dopamine is secreted in the retina to specifically enhance the activity of cone cells while also suppressing activity of rods.  This occurs only during daylight hours as a way to increase sensitivity to contrast and color during the conditions of bright light.  It also seems that dopamine plays a role in the eye's growth and potentially in control of myopia. Various animal studies have already shown that dopamine and dopamine-agonists can slow myopic changes. Thus, stem cells could be used to obtain highly functional dopaminergic cells which could then be used to treat myopia. In this instance, the stem cells are contributing an indirect effect.



The take-away is that stem cell treatments could be formulated to provide both direct and indirect help for this particular medical issue. Once again, the potential applications for stem cells continues to expand!

Tissue Repair Mechanisms by Stem Cells

The complete picture on how stem cells actually repair damaged tissue has yet to be fully defined.  There are a number of studied mechanisms, and it is most likely that there are a multitude of events that take place during this treatment process, and it is the combination of modalities that leads to repair success.

The original theory was that injected stem cells would directly change, or differentiate, into new tissue cells.  These new tissue cells were thought to be the actual injected stem cells that had turned into whatever cells the body needed at the site of injury. This has shown to be part of the overall picture, but not as much as initially thought.

A great article from 2010 studied human stem cells in mice that had experienced cardiac injury (I. Chimenti, R. R. Smith, et al., "Relative Roles of Direct Regeneration Versus Paracrine Effects of Human Cardiosphere-Derived Cells Transplanted Into Infarcted Mice", Circulation Research, Vol. 106, No. 5, pp.971-980, 2010).  This study demonstrated a contribution from differentiating stem cells along with the release of certain growth factors and beneficial molecules.  The authors concluded that differentiation only accounted for 20-50% of the repair process.  Stem cell released molecules such as growth factors, antioxidants, and anti-inflammatory factors actually seem to play a more important role.  All of these substances together help to promote the proliferation of cells, the migration of existing stem cells, and the boosting of the immune system. The researchers claimed that these mechanisms accounted for 50-80% of the repair mechanism.

In addition, when stem cells are given systemically (such as through an IV), multiple studies have shown that only a small portion of the stem cells end up at the site of injury or disease.  The majority end up scattered throughout the body, and the lifespan of these cells seems to be less than originally thought.  This supports the idea that other factors are involved in the repair process, not just stem cells changing into normal, healthy tissue cells.

In addition to the large array of growth factors that help with the repair process, it appears that other mechanisms also play some role.  A study by J. Spees, M. Whitney, et al. elucidated the role in mitochondrial transfer between stem cells and existing damaged cells ("Mitochondrial transfer between cells can rescue aerobic respiration", Proceedings of the National Academy of Sciences of the USA, Vol. 103, No. 5, pp. 1283-1288, 2006). Our mitochondria are responsible for the life of our cells, and there a variety of reasons why the mitochondria will not function properly.  This can occur in certain disease states, with advancing age, and with injury to tissues.  This study showed that stem cells can transfer mitochondrial DNA into damaged cells and thus rescue them from death.

Fusion of two cells may also play a role in this scenario, as a stem cell may fuse with an existing cell, again transferring genetic material and rescuing the cell from death.  This has been shown in more than one study, including a more recent set of studies edited by T. Dittmar and K. Zanker titled "Cell Fusion in Health and Disease", released in 2011.

These are just some of the mechanisms that appear to play a part in the healing effects of stem cells.  Research is ongoing and time will give us many more answers (and most likely, more questions as well). Stay tuned for more....

Regenerating the Liver with Stem Cells

A research group in Korea just published an article in Plos One describing their study of stem cells for potential use in the field of liver regeneration.  The research article (PLOS ONE DOI:10.1371/ journal.pone. 0108874  March 27, 2015) focuses on genetic engineering of adipose-derived stem cells (ie., from fat tissue) to turn these cells into viable, functioning liver cells (hepatocytes).  This differentiation occurred by engineering the cells to over-express certain genes, specifically the Oct4 and Sox2 genes.  This essentially means that they found the particular genes that trigger a stem cell to differentiate into the desired cell type, then engineered them to do just that.

The adipose stem cells have the potential to change into a wide variety of cell lines, but by altering their gene expression, the researchers coaxed these stem cells specifically into hepatocytes.  They studied these new cells through multiple scientific methods and concluded that the new cells were mature hepatocytes that seemed to be functional.  These cells had the ability to store glycogen and produce urea, both normal functions of natural liver cells.  (Glycogen is a polysaccharide of glucose that is a form of energy storage for cells.  Urea is a byproduct of the metabolism of amino acids, proteins, and ammonia in the liver.)  The team also compared these induced cells to non-differentiated stem cells; the control group did not show either glycogen storing or urea production capabilities.

This study is important because stem cell therapies have been shown to have beneficial effects in the area of liver regeneration, but there have been some mixed results in prior clinical trials.  The Korean study paves the way for a more specific induction of stem cells towards the desired end result.  The goal is to optimize the use of stem cells in order to some day replace damaged liver tissue or to allow for the secretion of protective cytokines in end-stage liver disease. (Cytokines are basically small proteins that are involved in cell signalling, and they are important components of the immune system and our responses to inflammation and cancer.)

Although this study is just an early stage look at genetic engineering of our stem cells, it once again shows the potential for how stem cells will change the way medical care is delivered in the future.  By using this or similar technology, we may one day be able to take stem cells from fat and turn on or off specific genes in order to produce the exact cell types that a given patient needs at any point in time.  This is when medicine becomes tailored to our individual bodies and our personal medical issues.

Welcome to another glimpse of the future!

Stem Cells Reduce Injury After Brain Ischemia

A just published study from researchers in Korea has concluded that administration of stem cells in rats can deter neuronal damage after transient global cerebral ischemia, such as occurs after cardiac arrest.  The article in Stem Cells Translational Medicine (2015:4:178-185) focused on this particular area due to the very poor prognosis in these situations and the lack of adequate treatments.

Global cerebral ischemia is basically the lack of blood flow and oxygenation to the brain, as is encountered during cardiac arrest.  The prognosis when this occurs is very poor, with 33-50% of patients who have survived a witnessed cardiac arrest having severe neurological deficits.  If a patient actually survives an unwitnessed cardiac arrest (which is rare, in and of itself), there has been a 100% rate of occurence for severe neurological deficit.

The only proven therapy to date, and the current standard of care, is to induce hypothermia. This lowering of body temperature is basically meant to decrease metabolism and swelling.  However, this therapy is hard to deliver in practice, with many technical difficulties that can interfere with its overall effectiveness.  Plus, there are complications associated with this, such as infection and blood clotting issues.

The Korean team found that stem cells given intravenously immediately after global ischemia had significant protective effects when compared to those rats not receiving stem cells.  They looked at a variety of different end-points to analyze the efficacy of this therapy, and all results were promising.

• Stem cells reduced neuronal death after ischemia, as measured in the hippocampus of the brain.  The hippocampus is known to be particularly vulnerable to delayed nerve death after an ischemic event. 
• Stem cells diminished the disruption of the blood-brain barrier, by either restoring the barrier or actually protecting it from disruption.  
• The stem cells also helped to reduce the damage to the blood vessels in the brain, and decreased the number of neutrophil blood cells that infiltrate the damaged area.  Neutrophils tend to accumulate in areas of inflammation, so this reduction implies a decrease in the inflammatory response after ischemia.
• Stem cell therapy reduced the behavioral impairment, again implying that the neurological deficit was significantly less when compared to the non-stem cell rats.

All of these factors showed promise for a possible future treatment in ischemia-related scenarios.  One limitation of this study is that it did not directly compare stem cell treatment with induced hypothermia (the current gold standard therapy).  That would be a good study to see undertaken in the future in order to have a direct comparison, but this research still seems to show that stem cells are an effective treatment. This is very early reaearch, but promising nonetheless.  

Hockey Legend Gordie Howe Has Stem Cell Therapy

Here is a synopsis on a story regarding stem cell therapy for stroke victims...

Detroit Red Wings hockey legend Gordie Howe is reported to be making a dramatic recovery after undergoing stem cell therapy in December, 2014.  He reportedly had the treatment performed in Tijuana, Mexico.  His health had been declining over the past many months due to a series of strokes.

The 86 year old legend actually attended a dementia fundraiser in Canada over the weekend of February 6, 2015, a trip that his family had previously said he was too ill to make.  However, he has had such a dramatic improvement in his health since the stem cell therapy that he was able to make the long trip.

His son, Mark Howe, publicly stated that prior to December his father had almost completely stopped functioning in any normal manner.  He noted an almost immediate improvement after the treatment, with his father now able to walk on his own, feed himself, and help fold laundry, all of which he was previously unable to do.

The therapy were performed in Mexico where there are less restrictions on stem cell treatments. Gordie was interested in a study in the US but one of the criteria is waiting until at least 6 months after the stroke.  There is some preliminary data suggesting that the earlier the treatment after a stroke, the better.  Thus the Howe family elected to have treatment sooner in Mexico.

To see more from an article in the San Diego Union-Tribune updated on Feb. 7, 2015, please follow this link:
http://www.utsandiego.com/news/2014/dec/25/gordie-howe-stem-cell-stemedica-novastem-hockey/

The Obesity - Cancer Connection

A team of researchers from Tulane University published a very intriguing report in the February 2015 issue of Stem Cells that focuses on the manner in which stem cells directly influence obesity-associated cancers.

These findings have profound effects in our understanding of adipose (fat) cells, adipose stem cells (ASC's), and cancer cells specifically related to obesity.  The interplay between these is not only fascinating, but also may lead to future treatments for a variety of these types of cancer.

This study is especially important at a time when the obesity rates globally continue to increase. It is estimated that one third of American adults are obese, meaning over 80 million people in this country alone.  The World Cancer Research Fund used meta-analysis research in 2007 to study the effects of obesity on incidence of cancer and the associated mortality.  They found that as fat levels increase, so do the rates of colorectal, renal, and postmenopausal breast carcinomas.  See the website at  http://www.wcrf.org/int/cancer-facts-figures/link-between-lifestyle-cancer-risk/cancers-linked-greater-body-fatness.  A number of other studies have also shown increases in cancer among obese patients - this includes prostate, endometrial, liver, ovarian, and esophageal cancers, along with hematological malignancies, and certain lymphomas and melanomas.

Here are some more links in regards to specific cancers:
General obesity - http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(02)00849-5/abstract?cc=y ; http://www.ncbi.nlm.nih.gov/pubmed/19824817
Prostate cancer - http://www.ncbi.nlm.nih.gov/pubmed/17507151
Endometrial cancer - http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.12106/abstract ;
                                   http://www.hindawi.com/journals/ogi/2011/308609/
Liver cancer - http://www.ncbi.nlm.nih.gov/pubmed/15508109
Ovarian cancer - http://www.ncbi.nlm.nih.gov/pubmed/23402904

This is only a very small amount of data in regards to this topic, as a complete list of the studies is too numerous to provide here.

This previous research found a link between obesity and certain cancers, yet the actual causal mechanism had not been found.  The just-published study suggests that stem cells are altered by obesity and integrate into the tumors themselves, providing support for tumor growth. Genes from ASC's in obese patients are expressed differently from those in normal wight individuals, and the data gathered tends to imply that the ASC's from obese patients have an increased propensity to assist cancer cells and further their survival.  The number of stem cells in circulation was significantly greater in obese patients, even further increasing the likelihood of these ASC's having the opportunity to migrate to the tumor site and encourage further cancer growth.  And finally, the ASC's from the obese population expressed a greater amount of certain chemical factors that aid cancer cell proliferation and even migration/metastasis.

These findings are just the beginning in terms of research on obesity-linked cancers.  Future investigation will focus on how obesity changes our stem cells and predisposes to an increased incidence of cancer, and will also hopefully lead to information that might help eventually reduce cancer risk.  Also, as growing research is showing, there will be ways to use stem cells to fight various cancers, by changing how the stem cells work and making them actually inhibit growth and even destroy cancer cells.

Cancer-Killing Stem Cells

Researchers at Harvard Medical School have engineered cancer-killing stem cells in laboratory mice. These scientists, working specifically at the Harvard Stem Cell Institute at Massachusetts General Hospital, released the results of this pioneering study in the February 2015 issue of Stem Cells.  Through experiments on mice, stem cells were genetically altered to produce and secrete toxins that specifically target brain tumors while causing no harm to themselves or normal brain cells in the process.

Genetic engineering allowed these researchers to develop a strain of stem cells that are resistant to the toxins they produce, while also secreting specific cytotoxins that kill glioblastoma tumors in the brain.  The toxins are specifically a Pseudomonas exotoxin, which has previously been used as an antitumor agent.  However, there had always been problems in the past with using this toxin clinically on patients; some of the issues encountered include difficulty reaching the tumor itself/off-target delivery, a short lifespan, and systemic toxicity.  By altering the stem cells to overcome these issues, it has allowed for a novel approach to using this type of technology in a meaningful way.  In the tests themselves, the stem cells were placed in a biodegradable synthetic gel and then placed at the site of the tumor, after it had been excised from the mouse brain.  The cancer cells were then exposed to the toxins and died, while leaving the stem cells and normal tissue unharmed.

The next step in this research will be to test other therapies on the glioblastoma cancer cells in mice using the same delivery method.  Then, eventually this technique will have to be tested on humans.  Glioblastoma is the most common brain tumor in human adults, so this research is very relevant to survival of these patients.

This type of research also opens the door to using similar techniques to treat a wide array of solid tumors.  Once again, this highlights the amazing abilities of stem cells in the future of modern medicine.

Stem Cells for Knee Pain

Case Report #2 - M.W.

This patient is a 48 year old female who presented complaining of pain in both knees due to arthritic changes.  An orthopedic surgeon had suggested to her that she would need bilateral total knee replacement surgery.  She did not want to undergo such drastic surgeries at this stage in her life and was eager to avoid it by trying an alternate therapy.

She had been active and athletic for most of her life, until a few years ago when her knees started giving her pain.  As the pain worsened, she gradually had to give up her normal exercise routine and over the past couple of years had gained weight as well. She is otherwise in good health with no other medical issues.  Unfortunately, she had been rather dependent upon non-steroidal anti-inflammatory drugs (NSAID's) to control her pain, typically taking ibuprofen daily.

Her radiology studies showed bilateral medial compartment osteoarthritis, or degenerative changes in both knee joints, especially the inner portion on each leg.  This is also consistent with where she experienced her pain. She actually had good range of motion when I saw her, and her pain was only evident when walking up or down steps.  She had no evidence of ligament or tendon involvement.

I have all patients fill out a comprehensive pain questionnaire that involves three different types of assessments for pain.  These include the Short Form McGill Pain Questionnaire(SF-MPQ), the Visual Analog Scale (VAS), and the Present Pain Inventory Score (PPI).  Her answers to these questions on the day of surgery were scored as 20, 67, and 3.5 respectively (for a total score of 91).

We developed a personalized pre-op plan involving supplements that appear to help viability of stem cells, along with her ceasing to take pain medications for the week prior to surgery.

She underwent manual liposuction and stem cell harvesting/isolation.  We also drew blood and obtained platelet-rich plasma (PRP).  I injected both knees with a mixture of stem cells and PRP, and she left our office with a plan to start physical therapy and also seek metabolic nutrition counseling through her medical plan.  She went to the physical therapist 2 days after the procedure.

I saw her back in the office on post-op day #8.  She stated that she felt less pain and that the exercises from the therapist seem to be helping strengthen her legs as well.  Her pain scores were as follows: SF-MPQ = 14, VAS = 28, and PPI = 1.5, for a total of 44.  This is roughly a 50% drop in her pain over one week.  She had also avoided using NSAID's since the procedure.  More impressive was the fact that in the past she had to help pull herself up her stairs at home by using the hand rail, due to knee pain.  Over the past 3 days, she had been walking up the stairs without requiring assistance.

She will continue with physical therapy and her selected supplements, and is awaiting the nutritional service consult as well.  This case just serves to illuminate the multiple factors that are involved in successful stem cell therapy.  First and foremost, it takes a motivated patient who is willing to actually put in the time and effort necessary to make success happen.  And it takes adjustments in diet and exercise to help augment the results.

Stem Cells to Improve Failing Vision

In yet another amazing story in regenerative medicine, a woman in Japan received a retinal stem cell graft as therapy for age-related macular degeneration (AMD), as first reported in September, 2014.  She is the first of six patients who are to have this treatment, being performed at the RIKEN Center for Developmental Biology in Kobe, Japan.

AMD is a major cause of visual loss and blindness in adults over the age of 50.  The most common type is known as "dry" AMD (or central geographic atrophy), wherein vision loss occurs due to the loss of the photoreceptors known as rods and cones.  There is no recognized medical or surgical treatment for this condition, although certain vitamin and supplement regimens may help.  About 90% of cases are "dry" AMD.  (The other type is known as "wet" AMD where vision loss occurs due to the abnormal growth of  blood vessels.  There are multiple medications that can help with this condition, although some require direct injections into the eye on a routine basis.  The goal is to reduce the growth of these blood vessels and eliminate them.)

The woman mentioned earlier had skin cells harvested and then reprogrammed into specialized retinal pigment epithelial cells.  This is a type of induced pluipotent stem cell (iPS), wherein a patient's own cells are induced into a stem cell line that is wanted for a particular type of tissue therapy. These cells were then grafted into her eye as a patch with the hope of allowing these cells to maintain her own rods and cones.

Shinya Yamanaka and colleagues at Kyoto University first discovered iPS cells in 2006; Yamanaka was awarded the Nobel Prize for this work in 2012.

Mike Cheetham of the Institute of Ophthalmology at University College London (another site researching human embryonic stem cells and AMD) had this to say in regards to the Japanese trial - "If it goes well, it could be the start of a new era in personalized medicine."