Stem Cell Therapy for Sports-Related Injuries

In the last 5 years, we have seen an increasing number of professional athletes turning to stem cell therapies to recover from injury. Tiger Woods, Rafael Nadal, and Max Scherzer have all been reported to have undergone stem cell therapy for their sports-related injuries. 

While stem cell therapy was once prohibitively expensive for most, prices have come down significantly, making it more accessible. In this article we will discuss what stem cells are, the various treatments available and their efficacy and cost.

What are stem cells?

Stem cells are cells in the body that have the potential to self-renew, develop into other types of cells, or divide into identical cells. When there is an adequate source of resources and the right environment, stem cells have the ability to change and become cells with highly specialized functions. Moreover, stem cells are the cells that are responsible in tissue repair and injury recovery in the muscles, liver, kidneys, and lungs (1). There are several types of stem cells:

• Pluripotent stem cells could become progenitors of any type of cell in the body. For example, embryonic cells could become stomach, lung, skin, or brain cells.
  
  
  
  

• Multipotent stem cells develop into different specialized cells of a specific tissue. Unlike pluripotent cells, the fate of multipotent cells is limited.
  
  
  
  

• Mesenchymal stem cells (MSCs) are an example of multipotent cells that can develop into bone cells, cartilage cells, and muscle cells. MSCs are currently very significant in stem cell therapy because they can readily be harvested from adult donors, unlike the other types of cells.
  
  
  
  

• Unipotent stem cells have the ability to become only one type of cell. For example, the satellite cells of the skeletal muscle are limited to becoming mature skeletal muscle cells (2).

What is stem cell therapy?

Stem cell therapy is a treatment approach that utilizes stem cells grown in the laboratory. These cells are used to replace lost tissues or to assist existing tissues in performing specific functions. 

Current techniques of stem cell therapy commonly utilize MSCs because they can be derived from various adult organs and tissues, making it easier to be acquired as compared to pluripotent cells. MSCs can be harvested from the placenta, fat cells, liver, lung, or blood vessels (3). 

Stem cells are first harvested or isolated from the donor tissue. The cells are then grown or cultured in the laboratory. When successfully cultured, stem cells are then injected to the recipient and are expected to home to the target organ, in most cases, to the injured site. The recipient is then monitored for possible inflammatory reactions following the injection of stem cells (3).

Stem cell therapy for injury repair

The US Department of Health and Human Services estimates that the average annual number of sports and recreation-related injuries is at 8.6 million per year (4). The ability of MSCs to become mature bone, cartilage, or and other connective tissues make them ideal sources of regenerative tissues for injury repair, especially for sports-related injuries. MSCs could function as regulators of growth and maintenance in these tissues (1). In addition, MSCs release different substances that stimulate the existing cells in the injured tissue to undergo cell division, hence increasing the number of cells and promoting tissue survival (5).

Current regenerative medicine techniques for sports-related injuries include 3 methods:

·       Platelet-rich plasma

·       Bone marrow concentrate

·       Direct grafting of stem cells

The use of BMC and PRP injections have been effective in addressing failed healing or delayed healing fractures. Other recent developments also show BMC and PRP to be effective in rib and mandibular fractures (6). Meanwhile, through the direct grafting of tissue-specific stem cells, MSCs that have matured into the desired tissue type can be integrated into the target tissue (5). Let’s take a quick look at each of these methods.

Platelet-rich plasma

PRP contains a high concentration of platelets and various biologic substances such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and many others. As the cells are derived from the patient the potential for adverse reactions and infection is very low. PRP is not made up of stem cells, but the use of PRP has been found to stimulate MSC proliferation. Thus, PRP is a vital component of stem cell-based therapy in sports-related injuries (7). 

A study published in 2012 showed that the local application of PRP in the repair of rotator cuff injury in patients reduced the pain after surgery. In addition, long-term results showed that PRP aided in the healing of rotator cuff injury in patients (8).
 

Bone marrow concentrate

Bone marrow concentrate (BMC) is another tool that is used for sports-related bone injuries and other lesions. BMC is a rich mixture of MSCs, different bioactive molecules, white blood cells, and platelets. Just like PRP, BMC is also harvested from the patient. This reduces the risk of infection and immune reactions. BMC is used to deliver stem cells to damaged bone, thus initiating repair and healing.

A clinical study done in 2016 showed that treatment of discogenic back pain with BMC injections provided relief of pain and disability improvement. BMC was delivered via disc injection to 26 patients, which showed improvement over the span of 2 years. This will not only benefit athletes with back injuries, but also the general public who could be chronically experiencing back pain (9). Another study published in 2015 reported that the use of BMC for open Achilles tendon repair resulted to excellent outcomes, characterized by early mobilization and zero re-ruptures (10).

Direct grafting of stem cells

Emerging biotech research studies have used the direct grafting of stem cells to focus on the production of tissue engineered bone bioscaffolds. These bioscaffolds are meant to function as a porous and permeable solid structure for stem cell attachment, growth, and migration. Such scaffold material would make it easier for stem cells to adhere to the injured tissue and promote growth of new cells (5). Most of the current studies on the use of stem cells on grafts to repair bone and muscle injuries are still experimental. No clinical trials have been reported so far.

How much does stem therapy cost?

The cost of stem cell therapies depends largely on the specific type of stem cells and tissues involved and the extent of injury. In the US, stem cell therapy for knee injuries range from $3000 to $5000 but the most expensive ones can reach up to $50,000. The same type of treatment costs as low as $2000 in Mexico and in Asian countries such as Thailand.

References

1. Stem cells and the evolving notion of cellular identity. Daley, G. 1680, 2015, Vol. 370.

2. Adult stem cells: hopes and hypes of regenerative medicine. Dulak, J., et al. 3, 2015, Vol. 62.

3. Browne, C., Chung, T. and Atkinson, K. The Biology of Mesenchymal Stem Cells in Health and Disease and Its Relevance to MSC-Based Cell Delivery Therapies. [book auth.] L. Chase and M. Vemuri. Mesenchymal Stem Cell Therapy. New York : Humana Press, 2013.

4. American Physical Therapy Association. Sports and Recreation-Related Injuries Top 8.6 Million Annually. APTA. [Online] January 4, 2017. https://www.apta.org/PTinMotion/News/2017/1/4/SportsInjuries/.

5. Young, M. and Doran, M. Mesenchymal Stem Cell Therapies for Bone and Tendon Conditions. [book auth.] L. Chase and M. Vemuri. Mesenchymal Stem Cell Therapy. New York : Humana Press, 2013.

6. Siddiqui, I., Mazzola, T. and Shiple, B. Techniques for Performing Regenerative Procedures for Orthopedic Conditions. [book auth.] G. Malanga and V. Ibrahim. Regenerative Treatments in Sports and Orthopedic Medicine. New York : Demos Medical Publishing, 2018.

IS HGH AN EFFECTIVE ANTI-AGING DRUG?

Growth Hormone (GH) has been shown to offset many of the side effects of aging. Supplementation can reduce body fat, increase lean muscle, improve skin elasticity, energy and sex drive. Many claim GH is a “fountain of youth”. However several studies point to a significant potential downside - increased GH levels may reduce lifespan. In this article we will discuss the latest findings and the pros and cons of GH supplementation for anti-aging.

WHAT IS A HUMAN GROWTH HORMONE?

HGH or GH is a hormone produced by the pea-sized pituitary gland that is located at the base of our brains. In the early stages of our lives it fuels growth, it also helps maintain tissues and organs throughout life. 

WHAT ARE THE EFFECTS OF GROWTH HORMONE?

GH stimulates body growth by stimulating the liver and other tissues to secrete IGF-1 (Insulin-like Growth Factor). IGF-1 is anabolic - it increases lean muscle mass and reduces fat tissue simultaneously. It also promotes neurogenesis which is the growth of new brain cells and has neuroprotective properties – it prevents brain cells from dying.

However, as we age there is a natural slowdown in GH production and consequently IGF-1. This can lead to muscle wasting, loss in bone density, reduced skin elasticity, increased fat retention, loss of immune function and cognitive decline – many of the signs we associate with aging. 

Many people supplement synthetic GH to prevent some of the side effects of aging. HGH promoties muscle, bone growth and also slows down apoptosis. Apoptosis is a programmed cell death that protects against the spreading of infectious diseases and cancer, but it can also lead to the death of healthy cells as we get older. GH also promotes new nerve growth in the brain which can lead to better cognitive performance and wellbeing (1) (2).

WHAT EFFFECT DOES IT HAVE ON THE IMMUNE SYSTEM?

Our immune systems deterioate with age. One of the organs responsible for our immune system to function properly is thymus – this is the primary lymphoid organ of the immune system. Within lymphoid organs T-cells mature. T-cells are type of white blood cells that are essential part of our immune system. They determine the specificity of immune response to foreign substances in the body or in other words – antigens.

The thymus is fully developed by the time we are 10 years old but then it starts shrinking. This gradual shrinking is related to the decline in our immune systems as we get older.

So called thymic involution (the shrinking of the thymus with age) leads to growing mortality risk, decrease in tissue mass and depletion of critical immune cell populations. That is linked to age-related increases in cancer incidence, infectious diseases, autoimmune conditions, generalized inflammation and atherosclerosis (3). 

Supplementation with GH has been shown to help rejuvinate the Thymus and therefore boost our immune systems.

THREE-DRUG COMBINATION TO BOOST THE IMMUNE SYSTEM

From 2015-2017 a human clinical trial was conducted in attempt to reverse various aspects of human aging. It was called TRIIM (Thymus Regeneration, Immunorestoration, Insulin Mitigation). In this trial they used growth hormone to reverse biological aging of the immune system in a population of 51 to 65 year old healthy men. 

GH is known to increase blood sugar levels so they used combined GH with DHEA and metformin to keep blood sugar levels in check. Metformin is used to treat people with type 2 diabetes and has been  proposed as a candidate for slowing aging in humans before. All of the mentioned drugs (GH, DHEA, metformin) have been linked to slowing the aging process in the laboratory (4).

During the trial the composition of thymus was checked and blood samples were taken to analyze immune cell counts. The trial's results were impressive, the patients Thymus' appeared to regenerate, fat tissue was replaced with regenerated, healthy tissue. Not only that, the parcipants' biological age was 1.5 years lower than when they first entered the trial! The sample size in this study was small but the results were very consistent

What is interesting is that this study showed that supplementing with GH for a relatively short time period led to a rejuvination of the thymus. Other studies have demonstrated similar results, short term supplementation such as 6 months can lead to significant changes in our organs, winding back the body clock by years (5).

SO WHAT IS THE DOWNSIDE?

While GH may help you to feel and look younger, increased levels of GH (or more specifically IGF-1) has been linked to shorter lifespan. This has led to a great deal of confusion in the anti-aging community, is GH a fountain of youth, or a potential accelerant of the aging process?

In experiments in mice, worms and flies the subjects with lower levels of GH lived longer. Mice with GH and insulin-like growth factor (IGF-1) deficiencies lived 50 % longer than mice of the same species with no deficiencies. It appears GH or at least IGF-1 promotes growth but also depresses life span across many species (6). In humans decreased IGF-1 is in fact correlated with the longevity of centenarians (people who has reached the age of 100 years).

Elevated levels of circulating IGF-1 might decrease lifespan because IGF-1 causes increased cell proliferation which can raise our suceptibility to diseases such as cancer (7). Too much of human growth hormone can also cause arthritis, diabetes and even heart failure.

Reduced growth hormone and IGF-1 may also increase lifespan by increasing the expresion of genes that are involved in stress resistance and DNA repair. 

However, we should be wary, the reduction of IGF-1 expression levels can come at an expensive cost especially when it comes to muscle and brain maintenance and repair. Results from various studies have been very inconsistent (8).

IS IT A TRADE OFF?

Ecologists and other evolutionary biologists have pointed out dozens of trade-offs in natural populations. Perhaps individuals that reproduce (or reproduce more) have a corresponding decrease in some fitness trait such as longevity (9). Evolution may be forced to accept costly tradeoff later in life in exchange for better chances for early individual reproductive success.

IGF-1 is good example of an evolutionary trade off. IGF-1 stimulates rapid growth (tissues and organs growth) and development in early stages of our lives but it can also have some negative long-term effects such as cancer and can increase mortality.

This theory works very well with the counterintuitive findings that most of the »longevity genes«  discovered in various organisms are either loss-of-function mutations or mutations that reduced the level of gene expression (8). 

The evidence to support this theory is still limited. There is a lot of IGF-1 early in our lives but the effects are not as harmful. Later in life IGF-1 is at very low levels so the correlation between higher levels of IGF-1 in our teens and risk of cancer and other diseases in our older years is very hard to explain.

how can we balance the benefits, while minimizing the risks?

FIRST TRY TO BOOST GH LEVELS NATURALLY

Some scientists claim enhancing GH and IGF the natural way may maximize the benefits without the costs. There are natural and effective ways we can increase natural growth hormone levels:

Strenuous exercise has been shown to increase growth hormone levels
but it is important to mention that we can get acclimated to exercise over
time which will lead to less hormone secretion from glands.

Intense heat stress induces a massive rise in GH - 30 minute sauna
therapy has been shown to cause a rapid boost in growth hormone levels.
A research study from 2007 found that group with a 30 minute
continuous sauna session showed higher elevations in hGH levels (10).

Eat a healthy diet, rich in healthy fats and low in sugar.

Get plenty of sleep.


DON'T GO CRAZY

If you choose to supplement with GH, make sure you see a doctor and get your blood tested first. Supplementation with exogenous GH is only recommended for people who are unable to boost their GH to healthy levels using the natural methods described above. 

Supplementation is usually only considered for people older than 40, this is when the drop in GH becomes more noticable. If supplementing make sure the dose you take doesn't take your GH levels higher than that of a health 30 year old. 

Only supplement for short periods of time (not more than 3 months) and take regular breaks. Supplementing for 3 months once per year should be more than enough to restore the thymus to healthy function. Not taking GH for extended periods will help to reduce the potential negative impact on longevity.

CONCLUSION

Growth hormone supplementation provides many physical and psychological benefits however the correlation between higher GH levels and shorter lifespans is worrying - therefore moderation is advised. Further research with larger and more diverse populations are needed before we will fully understand how to maximise the benefits and minimize the risks. In the meantime try boosting your GH levels naturally, through high intensity training, sauna, a healthy diet and making sure you get plenty of sleep. If you decide to supplement do so only under the supervision of a doctor and not for more than 3 months a year.

REFERENCES

1.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682398/

2.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305861/

3.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6276058/

4.   https://onlinelibrary.wiley.com/doi/full/10.1111/acel.13028

5.   https://singularityhub.com/2019/09/17/the-first-evidence-that-drugs-could-turn-back-the-clock-on-our-
biological-age/

6.   https://academic.oup.com/biomedgerontology/article/67A/6/652/583809

7.   Longo, V. D. and L. Fontana. 2010. Caloric restriction and cancer prevention: metabolic and molecular mechanisms. Trends Phamacol. Sci. 31:89-98.

8.   https://wjmh.org/DOIx.php?id=10.5534/wjmh.180018

9.   Leroi, A. M., A. Bartke, G. D. Benedictis, C. Franceschi, A. Gartner, E. Gonos, M. E. Feder, T. Kivisild, S. Lee, N. Kartal-Ozer, Schumacher, M., Sikora, E., Slagboom, E., Tatar, M., Yashin, A. I., Vijg, J, and B. Zwaan. 2005. What evidence is there for the existence of individuals genes with antagonistic pleiotropic effects ? Mech. Age. Dev. 126:421-429

10.  https://journals.indexcopernicus.com/search/article?icid=890538 

Is a parasitic fungus the secret to athletic performance?

What is Cordyceps?

Cordyceps sounds like something out of a horror movie, it is a parasitic fungus that infects its host and devours it from the inside out, eventually killing it. Once it finishes consuming the hosts body, it sprouts a mushroom from the hosts head, and releases its spores to begin the whole cycle again with another host. Fortunately for us Cordyceps only infect insects.

What is it used for?

Cordyceps have long been used in traditional Chinese medicine to increase energy, treat asthma and improve sexual function. It is said that the benefits of Cordyceps consumption were first discovered when herders in the Himalayas observed that yak, goat and sheep which had eaten the mushroom became very strong and stout. The local people then used the fungus to improve the vitality of their cattle, and it was not long before the locals themselves started consuming it. The locals claimed it had aphrodisiac effects and it became known as Himalayan Viagra(1).

Cordyceps hit the headlines in 1993 during the Beijing Olympic games when several Chinese runners smashed various world records and attributed their success to eating Cordyceps mushrooms.

Wang Junxia beat the 10,000 meters women's world record by an astonishing 42 seconds, she also broke the 3000 meters world record and her teammate set a new world record in the 1,500 meters. It sounded too good to be true, could a mushroom do all this? Probably not.

Wang Junxia of China, center.

Credit Ed Reinke/Associated Press

Does it really work?

It appears this team may have been taking much more than mushrooms. In 2016 a letter reportedly from Wang and nine other athletes was published which alleged Coach Ma forced them to dope(2). In addition Coach Ma was fired from the Chinese national team in 2000 after 6 of his athletes tested positive for performance enhancing substances. However just because of this scandal the ability for Cordyceps to positively affect athletic performance should not be written off as several recent studies have shown some impressive results.

“Cordiceps has a significant positive effect
on athletic performance”

One human study showed that supplementation over a three week period (4 grams per day) resulted in significant improvements in the body's ability to absorb oxygen, improvements in exercise endurance and in some measures of heart health(3). Another study showed that exercise performance for healthy older people was significantly improved upon taking Cordyceps versus the placebo group (4)

The mechanism by which Cordyceps improves athletic performance is not fully understood but it is believed that Cordyceps helps improve blood flow as well as the body's ability to burn fat and process glycogen(5) (glycogen is the carbohydrate energy store within our muscles). Together these effects increase the availability adenosine triphosphate (ATP) in the body, ATP is the source of energy the body uses to power the contraction of muscles.

In addition Cordyceps have been shown to delay lactate accumulation(6). Lactate accumulation is responsible for that burning feeling in muscles during intense exercise, consuming Cordyceps means you can exercise harder for longer.

But the benefits of Cordyceps are not limited to athletic performance; Cordyceps are also a powerful antioxidant(7), have been shown to help regulate the immune system(8), may help fight certain types of cancer(9) and may be beneficial for brain function(10).

It is important to note that most of the studies on athletic performance only observed benefits when supplementation continued for several weeks, very little benefit was shown from short term (one week or less) supplementation. Therefore if you choose to supplement with Cordyceps, you will need to keep it up for several weeks before you can expect to see results.

But not all Cordyceps are created equal!

The form of Cordyceps most commonly shown in pictures, where you see a mushroom sprouting out the head of a caterpillar is Cordyceps sinensis, it grows wild at high altitude in the Himalayas.

Cordyceps sinensis growing on caterpillars

Due to high demand and limited availability, wild Cordyceps now cost around $50,000 a kilo! Beware of any supplements which state they contain wild Cordyceps Sinensis, due to the high price tag these supplements often contain very little of the mushroom.

Fortunately there are other varieties of Cordyceps which can be grown in the lab which are far cheaper – and vegan friendly!

One of these is Cordyceps CS-4, Cordyceps Cs-4 is a mycelium culture which is grown in liquid vats, Cs-4 is unable to produce a mushroom but the mycelium which is cultivated has many of the same health benefits.

Another variety is Cordyceps militaris, which grows in Europe, and actually contains more cordycepin than the other species! Cordycepin is one of the constituents of Cordyceps which has anti-cancer, anti-oxidant and anti-inflammatory activities(10).

Cordyceps militarism

Just beware of Cordyceps supplements which are grown on grain, often these contain mostly grain and very little of the mushroom or mycelium itself. Unfortunately it is not easy to identify such supplements but one red flag is if the label says anything like "myceliated brown rice/grain".

Unfortunately you won't find Cordyceps in your grocery isle but a range of supplements and extracts can be found online. Below is a selection of brands which offer products high in beneficial mycelium or mushroom content.

Another great way to get your daily dose of Cordyceps is to take it in your coffee or hot chocolate, the guys at Four Sigmatic produce some great mushroom blends.

 

References

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121254/

2. https://www.nytimes.com/2016/02/25/world/asia/china-olympics-doping-ma-junren.html

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5236007/

4. https://www.ncbi.nlm.nih.gov/pubmed/20804368

5. https://www.ncbi.nlm.nih.gov/pubmed/21549819

6. https://devjournals2013.lww.com/acsmmsse/Fulltext/2001/05001/SUPPLEMENTATION_WITH_CORDYCEPS_Cs_4_FERMENTATION.928.aspx

7. https://www.ncbi.nlm.nih.gov/pubmed/17386115

8. https://www.ncbi.nlm.nih.gov/pubmed/19222900

9. Feng K, Yang Y. Q, Li S. P. Renggongchongcao. In: Li S. P, Wang Y. T, editors. Pharmacological Activity-Based Quality Control of Chinese Herbs. New York: Nova Science Publisher, Inc.; 2008. pp. 155–78.

10. https://www.sciencedirect.com/science/article/pii/S1382668916300308

11. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909570/