Many people have heard the term stem cell therapy in the media and on the internet. It’s been discussed theoretically for years as a promising new therapy to treat anything from congenital disorders to organ failure to the ails of aging. We get a lot of questions in our office about stem cell therapy, usually from patients with a musculoskeletal issue, they’re looking to treat or for longevity and anti-aging. So we wanted to answer many of the questions that come up regarding stem cell treatments and what the future of regenerative medicine looks like.
Regenerative Injection Therapies Used to Treat Injuries
For years people have been using regenerative therapies to treat injuries and wear and tear on the musculoskeletal system like arthritis, sports injuries, strains, sprains, etc. The oldest of these is prolotherapy, which is short for proliferative therapy. The principal of this treatment is to inject a mild irritant near the damaged structure, usually, a sterilized sugar-water solution, to intentionally create a small amount of inflammation in the area, which would in turn attract more blood flow and repair cells. There are some very positive results patients have seen with prolotherapy including tendinopathies, knee and finger joint OA, and spinal/pelvic pain due to ligament dysfunction . Some studies have shown little improvement with administration of prolotherapy such as with Achilles tendinopathy, plantar fasciopathy and OsgoodSchlatter disease . The upside of prolotherapy is that it’s relatively inexpensive and widely available. The downside is that patients tend to be more sore after receiving the injections, may require many more injections to attain a similar result from other injection therapies, and results can be more variable.
At Pure Vitality, we offer Prolotherapy.
PRP Injection Therapy: the Game Changer
The next great leap in regenerative joint injection therapy was the discovery and utilization of PRP. PRP stands for Platelet Rich Plasma and is a component of blood. All of us contain platelets in our blood that help produce clots when we have tissue damage or get cut. The platelets help form a physical block to the damaged vessels which helps stop bleeding. Years ago we thought that was the only utility platelets had. Much later in the 2000s they started being used for helping surgical grafts to heal and other uses for platelets were explored. We discovered that platelets contain powerful tissue growth factors like transforming growth factor beta and platelet-derived growth factor .
These growth factors present a tremendous potential for stimulating tissue growth in damaged areas of the body . Techniques were
developed to concentrate the platelet layer from a blood sample and this concentrated platelet later can then be injected into a damaged area often with miraculous results [5,6,7]. Many patients find that they need fewer injections of PRP to get equivalent results compared to prolotherapy and often experience less soreness after injections. The downside is that the treatments are more expensive and will require the patient receive a blood draw in order to extract the platelets. Many famous athletes like Tiger Woods, Hines Ward, and Rafael Nadal have received PRP injections to successfully heal sports injuries [8,9]. At Pure Vitality we offer PRP Injection Therapy
Stem Cell Injection Therapy: The Holy Grail?
The next great advancement in regenerative injection therapies is stem cell therapy. There have been many famous athletes that have gotten media attention for going to places like Germany to receive stem cell treatments. First, let’s outline the three most common sources for harvesting stem cells. All of us have stem cells in our bodies that lie dormant until they’re induced to differentiate and multiply. The first two sources are from the patient themselves. Fat tissue and bone marrow present two of the most easily accessible sources of stem cells in the body. Both require a large needle to extract the stem cells and there are various amounts of discomfort associated with the procedure. After the tissue extraction, the cells often need to be separated from the surrounding connective tissue and concentrated prior to injecting. Handling these tissue requires a specialized room and to keep the cells alive they need to be fed glucose and kept at body temperature.
So what’s the difference between adipose-derived and bone marrow-derived stem cells? Both are considered autologous since the stem cells are being harvested from your own body. Both tissue types also contain mesenchymal stem cells (MSC). Bone marrow-derived stem cell transplant is the more established procedure that has been used longer. However, bone marrow contains many more nucleated cells (including white blood cells that can impede the healing response) that need to be separated and the overall MCS count from bone marrow is far lower that adipose-derived stem cells. Additionally, many people find a bone marrow aspiration procedure to be very painful. Adipose-derived stem cell harvesting tends to be less uncomfortable, has fewer nucleated cells to filter out, and can yield up with 10x more MCS per sample. Another important feature to consider when looking for a stem cell procedure is which yields more colony forming units (CFU). This is the ability for a group of stem cells to actively divide and become a tissue graft. In the case of adipose MCS, they have up to a 50 fold greater ability to create CFU. Other studies have found adipose-derive stem cells to have higher proliferation capacity especially in regard to neuronal tissue. So adipose-derived stem cells may be a better bet when seeking an autologous stem cell transplant.
The other main option that is becoming more widely available is harvesting and using MCS from healthy placentas, umbilical cords, and amniotic fluid. These cells can be harvested and banked for that individual to use when they’re older if the need arises. The idea is that if you encounter a major problem with one of your organs or undergo major surgery, these stem cells could potentially be employed to regenerate new tissues, even possibly entire organs. Similarly, these MSC can be used in other individuals other than the host. The cells contained in these tissues are different from your own MCS in that they’re younger and they’re not yours. Ordinarily, when someone receives tissue from a donor there are concerns about tissue rejection. That’s why in order for a patient to receive a liver or kidney from someone else, they often need to be on tissue rejection drugs. All of our cells have an identification protein, which identifies them as our cells as uniquely different from another person’s cells. When our immune system encounters something with a different name-tag or MHC, it goes on the attack. That’s the basis for tissue rejection. So the drugs people
are given who receive foreign organs are immune suppressants. With MSC from placentas, cords, and amniotic fluid, however, have very little MHC expression so they don’t tend to trigger any immune compatibility issues if used in other people [12,13].
Aside from stem cells themselves, there are tissue fragments, growth factors, and other potentially beneficial agents found in umbilical cords, placentas, and amnionic fluid . Some companies have developed techniques to process and stabilize these elements for therapeutic administration. They may have an overall stimulating effect and aid in tissue regeneration but they are not themselves viable stem cells despite what some companies may claim.
Placental derive stem cells seem to have some tangible differences from autologous stem cells, the first being that they seem to have a greater immunomodulatory action [15,16]. Placental and cord cells also express high amounts of hepatocyte growth factor and CD200. Hepatocyte growth factor is important in angiogenesis (growth of new blood vessels), the formation of muscle, stimulates T-cells and is involved in optimizing wound healing [17,18].
If one decides to go the route of a MCS treatment from cord, placenta or amnionic fluid which company should you go with? That’s a big question and one that’s not always a clear answer. Most of the companies out there claiming to offer stem cell products likely are not containing live viable stem cells, at least in appreciable concentrations. Some of the companies are selling room-temp stable products with growth factors, some are selling product that needs to be on liquid nitrogen. Clearly, the room temperature products don’t contain viable stem cells. Stem cells once they’re removed from living tissue either have to be used immediately in a living host or they need to be kept at body temp and fed sugars, or they need to be cryopreserved. So room temp versions of products are clearly not containing living cells. They still likely contain growth factors and these can be used for therapeutic potential just like PRP, however ,whether they’re superior to PRP remains to be seen.
Another factor to consider when selecting a MSC company to use is whether they can provide flow cytometry results. Flow cytometry is how you can evaluate cell number and type in a sample. If a company is hesitant to provide that information or doesn’t have it, they are likely selling a non-living product. Some companies will try and get around providing this information by giving other markers of viability like CFU.
CFU stands for colony forming unit and is a marker of tissue growth. Since many stem cell products and extracts contain growth factors, there is some amount of CFUs that can be expected even if the stem cells themselves are not living. So this is not a replacement for flow cytometry results.
I would also like to point out that among the various MCS products, some companies differentiate products that are intended for joint or soft-tissue injections versus applications for intravenous use. The intravenous use products should have a more flowable consistency to minimize risk of vessel obstruction.
Some have argued that since placental and cord derived stem cells are primordial, they may have greater healing potential than harvesting one’s own aged cells. Whether or not this is true remains to be seen. Both sources of MSC seem to have therapy potential. Just be forewarned that if you choose a MCS product from cord, placenta or amnionic fluid, it may not actually contain viable cells.
So when and where can someone most successfully use each of these three regenerative injection therapies?
Obviously that’s on a case-by-case basis and the reason doctors such as myself have an in-depth initial visit. For musculoskeletal issues, all three options are viable ones. Cost is definitely a consideration. Prolotherapy is cheapest option for treating musculoskeletal issues. In fact there is an organization that has done volunteer work in Honduras for many years to give access to regenerative joint injections for underserved peoples. The cost of supplies is low, mostly you’re paying for someone’s expertise in treating the specific condition or their level of training. Prolotherapy has also been around the longest and is very well-established.
PRP is another great option for treating musculoskeletal issues. Is does incur higher cost since the materials are more expensive and the patient must allow a blood draw to harvest the sample for processing. I personally love PRP and find people experience excellent results with a wide variety of conditions. I have personally had the most success using PRP to treat whiplash injuries, hip osteoarthritis, knee osteoarthritis, knee ligament tears, ankle ligament tears, and shoulder labrum tears. I have not yet seen PRP therapy be successful for plantar fasciitis likely owing to that condition being more of a biomechanical issue that needs to be corrected.
With regard to the most expensive and newest option on the table, Stem Cell treatments have definitely garnered a lot of hype. I feel that if you’re administering the correct stem cell product, there is huge potential for healing. Keep in mind that your options here are autologous cells pulled from your own bone marrow or fat tissue for injection or purchasing a cord, placenta, amnionic product. Knees and other encapsulated joints with low amount of blood flow may not be the best site for a live stem cell injection since the synovial fluid may not sustain stem cell growth. However knees and all other sites may be good candidates for growth factor administration just like with PRP. I know many physicians who swear by fatderived injections for musculoskeletal issues and some neurodegenerative issues. The literature not unified, however, with regard to which conditions respond best to which stem cell preparation. There is a lot of variabilities in patients and in stem cell products. It is important to discuss that with the patient to provide full informed consent about any treatment that’s on the table.
Dr. Heath McAllister, ND
Check out our Regenerative Joint Injection Therapy page
1. Clin Med Insights Arthritis Musculoskelet Disord. 2016; 9: 139–159.
2. J Foot Ankle Res. 2015; 8: 57.
3. Castillo TN, Pouliot MA, Kim HJ, Dragoo JL. Comparison of growth factor and platelet concentration from commercial platelet‐
rich plasma separation systems. Am J Sports Med 2011;39:266‐271
4. Bone Joint Res. 2016 Mar; 5(3): 92–94.
5. Am J Sports Med 2008;36:1337‐1346
6. Joint Res 2014;3:193‐202
7. Curr Pharm Biotechnol. 2012 Jun;13(7):1185‐95
10. In Vitro Cell Dev Biol Anim. 2015 Feb;51(2):142‐50. doi: 10.1007/s11626‐014‐9814‐6.
11. Chin Med J (Engl). 2014;127(2):329‐37.
12. Stem Cell Res Ther. 2014; 5(2): 48.
13. J Biomed Sci. 2003 Mar‐Apr; 10(2):228‐41.
14. Exp Mol Med. 2012 Jan 31; 44(1): 1–9.
15. Stem Cells Int. 2012; 2012():658356.
16. Hum Immunol. 2009 Jan; 70(1):16‐23.
17. J Cell Biol. 2006 Jul 31; 174(3): 323–327.
18. Science. 1991 Feb 15;251(4995):802‐4