APPLICATION OF STEM CELL TECHNOLOGY FOR ANTI-AGING

Stem cell therapies are becoming increasingly popular for anti-aging. Makeup, moisturizers and face masks line the shelves touting the benefits of various “stem cell” formulations. Celebrities and middle age business men and women are flocking to exotic locations to inject themselves with stem cells sucked from their belly fat. Is this all in vein or is there some credible science behind this?

Stem cells show a lot of promise for the treatment of aging and various age-related diseases but the science is new and there are very few high quality studies. In addition, there are many different formulations and delivery methods, each of which is not equally effective. 

In this article we will discuss the various applications of stem cells in anti-aging, and the efficacy of each approach.

WHAT ARE STEM CELLS?

Stem cells are cells which have the ability to divide and transform into other types of cells. They are involved in building every type of tissue in the human body. This is why stem cells have great potential for therapeutic uses in tissue regeneration and repair. 

Unfortunately, the number and function of stem cells in our bodies declines with age, this is one of the reasons why our bodies natural healing and repair processes decline with age, and is a contributing factor to many age-related diseases.

THERE ARE SEVERAL TYPES OF STEM CELLS

• Pluripotent stem cells could become any type of cell in the body. For example, embryonic cells are pluripotent and can 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.

VARIOUS DELIVERY METHODS OF STEM CELLS

When treating patients for injury or anti-aging purposes there are a variety of stem cell delivery methods, some of the most common approaches are:

Direct injection

This is where the stem cells are injected directly into the site which is being targeted. For example, for arthritis the stem cells would be injected into the affected joint. Or for facial aging, the cells might be injected into the surface of the skin. While there is limited evidence, direct injection of stem cells appears promising.

Grafts

In a graft a bio scaffolds is created to function as a porous and permeable solid structure for stem cell attachment, growth, and migration. This scaffold is then surgically inserted into the site of injury. While there is limited evidence, grafts appear to be a promising method for delivering stem cells to facilitate repair in problem areas.

IV

Some treatments deliver stem cells intravenously. Some doctors claim that the stem cells will be able to target the problem areas in the body and deliver systemic anti-aging benefits. Unfortunately, the evidence to back up this claim is lacking, most stem cells which are injected intravenously end up trapped in the lungs, liver and kidneys (1).

Topical Creams

Some products such as face creams and masks claim they contain stem cell formulations which can be topically applied. There is no evidence that such a formulation would be beneficial as stem cells will not survive in this environment.

ARE STEM CELLS EFFECTIVE FOR ANTIAGING?

Aging is leading risk factor for many diseases, one of the primary causes of diseases like arterial atherosclerosis, Alzheimer’s and Parkinson’s, is the decline in the self-repairing capabilities of our cells as we age. A decline in the rate of cell division and the rate at which stem cells transform into other types of cells is a characteristic of aging. This decline in cell division reduces our ability to repair tissues and maintain organs as we get older. Therefore, stem cell technology is a likely candidate to slow or even reverse the aging process. 

Stem cell treatments have shown promise in promoting our bodies self-repairing capability, and therefore could have powerful anti-aging benefits. As stem cells replace our damaged or non-functioning cells, they help us maintain normal function of our tissues and organs (2) (3). 

Stem cells are also known to secrete various biologically active proteins such as growth factors, cytokines and other proteins that are important in cell signaling and vital immune function. This plays a very important role in tissue regeneration.  For example, mesenchymal stem cells (MSCs) can secrete signal protein - vascular endothelial growth factor (VEGF) that stimulates the formation and regeneration of blood vessels. This provides a big advantage for elderly body's ability to repair and regenerate especially because it's more prone to certain diseases (4).

WHAT ARE THE RESULTS SO FAR?

For Longevity

There currently are no conclusive studies in humans demonstrating that stem cell treatments can increase lifespan, however studies in mice show some promise. In one study stem cells were intravenously transplanted to 10-month-old rats once a month throughout their lives. This led to cognitive and physical improvements and their life span was extended by between 23% and 31% (5).

Caution should be exercised when extrapolating these results to humans. These rats were given very large doses and they were given repeatedly throughout their lifetime. In humans the vast majority of stem cells delivered intravenously end up trapped in the lungs, liver and kidneys, very little makes its was to other vital organs such as the heart and brain. In addition, it is not feasible nor affordable for most people to get treatment every month for the rest of their lives.

FACIAL AGING

The production of collagen starts to decline as we age which leads to wrinkles and sagging skin. One study has shown that many small injections of the stem cells just below the surface of the facial skin led to significant improvements in several markers of skin aging. Stem cells helped with formation of new blood vessels from pre-existing ones, survival of the cells & their division, boosted immune response and they helped with overall collagen degradation (6). 

In addition, fat-derived stem cells are often used in plastic surgery as seed cells. They play important role in prevention of photoaging (premature aging of the skin caused by repeated exposure to ultraviolet radiation (UV) – sun light). As we age, melanocytes (cells that synthesize skin pigment - melanin) become victim to excess sun exposure, inflammation and hormonal changes which can lead to development of unsightly dark spots and hyperpigmentation. This therapy has been shown to help with these aging symptoms.

FOR THE BRAIN

The function of neural cells in our brains declines with age. Aging in the central nervous system is associated with progressive loss of function which is exacerbated by neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. 

Cell therapy may be able to replenish lost cells and restore brain function. There are two primary strategies to achieve cell replacement. The first is transplantation of exogenous stem cells and the second is stimulating the body’s own activation of its neural stem cell population (7).

As most people would not risk injecting stem cells into their brains for potential anti-aging benefits these experimental treatments are reserved for only the most serious brain injuries. However, stimulating the body’s own production of stem cells may be beneficial, this can be done via supplements which are outlined in our anti-aging guide. (8)

FOR THE IMMUNE SYSTEM

It is well established that our immune system becomes less effective as we age. The decline in immune function which we experience with age, is partly due to the loss in efficacy of our bodies blood cells, largely as a result of decreased production of certain blood cells know as B and T lymphocytes. This can lead to various diseases including cancer. 

Hematopoietic stems cells (HSC's) are stem cells which give rise to other blood cells. Some research has suggested that reconstituting HSC or pluripotent stems cells may rejuvenate the supply of stem cells and help boost our immune systems (9).

HSC’s have been used to boost the immune systems of cancer patients for years via bone marrow transplants, however this treatment should only be reserved for extreme life-saving cases and is not suitable for anti-aging purposes. 

A safer alternative may be rejuvenating our existing stem cell populations, this could be achieved through NAD+ supplementation (see our anti-aging report). 

SKELETAL MUSCLES


One of the reasons our muscles can repair so quickly is we have a very large pool of stem cells in our muscles. As we age, we experience a loss of muscle function partly as out muscle stem cell pool is depleted. 

Some therapies have been shown to restore the ability of muscle stems cells to rejuvenate. One of these treatments is NAD+ recruitment as mentioned in our anti-aging report. Supplementation with NAD+ precursors like NR can help protect from the loss of muscle stem cells, this has been demonstrated this effect in mice (10).

FOR OSTEOARTHRITIS

In clinical trials stem cells have been used to regenerate cartilage and safely treat Osteoarthritis (OA).  Stem cells can have beneficial effects in regulating the microenvironment of damaged tissue, leading to more favorable conditions for tissue regeneration. Stem cells have been used in cell therapy to promote the repair of cartilage, muscle, and bone.

There was no serious side effects demonstrated however due to regulatory issues in the US only Stromal Vascular Fraction (SVF), a cellular extract that is made in a laboratory from fat is currently approved for clinical uses in humans. SVF only contains a small amount of stem cells (11). 

STEM CELL THERAPY – COST, BENEFITS & SIDE EFFECTS

Stem cell therapy can cost anywhere between $500 to $50,000. 

The cost depends on many variables such as the type of stem cells that are being used, where you are performing the treatment, where the laboratory is located, and if the cells that are being used are ethically sourced & regulated.

SIDE EFFECTS & RISKS

Some serious side effects that can occur include: 

• Administration site reactions

• The ability of cells to move from placement sites and change into
  inappropriate cell types or multiply

• Failure of cells to work as expected

• The growth of tumors.
  

Unproven stem cell treatments can be unsafe, so remember - make sure to do your research and ask as many questions as you can before you to commit to an actual treatment. If you are considering treatment in the United States, ask your health care provider if the FDA has reviewed the treatment.

CONCLUSION
 

The results from clinical trials and studies have demonstrated that stem cell have great potential for regeneration medicine and help with age-related problems such as slower regeneration time and degradation of our tissues. However, stem cell treatments are still regarded as experimental in the US. With further development of stem cell technology, it is only a matter of time before it becomes an effective treatment for aging-related diseases and offer new kind of alternatives for antiaging.

Being treated with stem cells is also not without significant risks, including the potential to cause cancer.  Therefore, restraint is advised. Stem cell therapies should only be considered where other options are not effective. If you choose to have a stem cell treatment make sure you go to an approved and accredited facility. Also, it is best to consider treatments which have already shown some promise such as site injections or scaffolds, avoid anyone touting the benefits of a systemic intravenous injection.  

REFERENCES

1) https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5260805/

2) Tsang SH (2013) Stem cell biology and regenerative medicine in ophthalmology. Springer, New York

3) Somasundaram I (2014) Stem cell therapy for organ failure. Springer, New Delhi

4) https://www.ncbi.nlm.nih.gov/pubmed/25797907

5) https://www.ncbi.nlm.nih.gov/pubmed/26315571

6) https://doi.org/10.1155/2016/7315830

7) https://doi.org/10.1111/j.1582-4934.2002.tb00451.x

8) https://www.nature.com/articles/s41536-017-0033-0

9) https://doi.org/10.5966/sctm.2014-0132

10) https://doi.org/10.1126/science.aaf2693

11) https://doi.org/10.1186/s13018-016-0378-x

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.