Hypertonic dextrose stimulates stem cell growth
With the different types of Prolotherapy available, a wide array of solutions are being used to heal people of their painful conditions, from dextrose, to platelet rich plasma (PRP), to stem cell injection therapy. At Caring Medical we utilize the comprehensive Prolotherapy approach – meaning we treat the entire affected area with the most effective solution(s), individualized for each patient. We offer all of the different types of Prolotherapy, including PRP and stem cell Prolotherapy. Many people are particularly interested in stem cell Prolotherapy, in part due to a variety of famous athletes receiving stem cell injections to help them resume their professional careers and recover from a variety of sports injuries. Many are looking for a non-surgical alternative to joint replacement surgery or an alternative to arthroscopy. Because of this, I am asked, “What is the effect of (hypertonic) dextrose on stem cell growth?” As many of you know, the science of stem cells is growing at an exponential rate. Let me provide you with some of the research in the published medical literature related to hypertonic dextrose in regard to stem cells. Here are a few published articles:
Hypertonic dextrose increases cartilage cell construct.
The goal of some stem cell therapies is the replacement of articular cartilage. Just to refresh everyone’s memory, the cartilage of the human knee is typically about 4mm in thickness, although underneath the knee cap can be 6mm in depth. Any cartilage implant or construct must maintain cellular viability throughout the construct thickness. Furthermore, the cells must continue to be metabolically active in order to synthesize mechanically functional extracellular matrix (makes up the cartilage). In other words, the implanted material or cells must stay alive and make cartilage (extracellular matrix). If either of these does not happen, then the material that is made is weak and won’t stand up to the rigors placed on it (like jumping and running).
Some researchers at Queen Mary University in London, decided to see what happens to a chondrocyte-seeded alginate construct when various concentrations of dextrose were added to the culture medium.1 They found that increases in the glucose concentrations in the medium from 5.1mM to 20.4mM increased the construct mass by 10% and the extracellular matrix formation (as evidence by glycosaminoglycan content) by 73%.
Human adipose-derived stem cells thrive in hypertonic dextrose environment and aid in osteogenic differentiation.
One source of stem cells is adipose (fat) tissue. Adipose-derived stem cells are an excellent source of multipotent stem cells and are capable of differentiating into a variety of other cells that are useful for musculoskeletal conditions. Researchers subjected human-adipose-derived stem cells to concentrations of glucose from 0.6 to 6.1 mM.2 Of interest in this study was not only did the higher concentrations of glucose cause the stem cells to proliferate but their differentiation into osteogenic stem cell lines was only observed when the glucose concentrations were physiologically normal to high levels. If this research is applied to humans in vivo (in the body) versus in vitro (in a cell culture) then for a stem cell to differentiate into a cartilage, for instance, a normal or high glucose level is needed. Remember stem cells are cells that can differentiate or change into other cells. (See Figure below.)
Hypertonic dextrose stimulates bone marrow-derived mesenchymal stem cells to proliferate.
One important published paper on stem cell research from Purdue University in West Lafayette, Indiana confirmed the notion that dextrose, especially hypertonic dextrose is a significant factor in the ability of mesenchymal stem cells from bone marrow to proliferate.3 The researchers varied the glucose concentration both a two- as well as three dimensional-medium and looked at stem cell numbers (proliferation). Glucose concentrations ranged from 0.5 to 25 mM. Serum glucose concentrations ranged from 2 to 10%. As would be expected the mesenchymal stem cell consumption of glucose increased proportionally with the glucose concentration in the medium. The higher the glucose concentration in the medium, the greater the glucose consumption by the bone marrow stem cells. The primary results note that the higher glucose and serum concentrations appear to produce higher cell populations over time. (See Figure 2 from the study.)
Glucose is the primary substance stem cells use for energy.
Sometimes we forget the cells of the body obtain their energy via aerobic metabolism. The primary substrates or substances that are needed for aerobic metabolism are oxygen and glucose. The body breathes to get oxygen and we eat to breakdown the food into sugar. Even if a person just eats protein, ultimately the body finds a way to breakdown the protein into individual amino acids and eventually into glucose. Without glucose the cells and the body cannot live.
When a physician injects hypertonic dextrose into a joint, immediately the dextrose concentration is cut in half because of the joint fluid inside the joint. Thus, when Caring Medical injects 15% dextrose into a knee joint for instance, it immediately becomes 7.5%, assuming the person has a normal amount of fluid in the joint. This percentage is within the parameters of what has been studied in vitro, as the above published research papers note. Realize, however, that there is a difference between in vitro (in a cell culture) and in vivo (inside the body). In a cell culture the solutions are maintained at the elevated dextrose concentrations. This does not happen in the human body. The human body is magnitudes more complex than a simple culture. In the human body when Prolotherapy solution is injected into a joint it induces a change in these structures to stimulate their healing and then the body quickly equilibrates. A good example of this is what occurs during athletic performance.
Dr. Hauser running example.
Generally when I run, I run about 7 miles in an hour. During race conditions I can run about 9 miles in an hour. When I am taking my time, I will run 6 miles in an hour. I have finished two 50-mile running races (ultramarathons). When I run my normal 7 mile runs in an hour, I am a little sore but within a couple of hours I feel fine. In other words, I induce some changes in my body to make it healthier and stronger. The 7 mile runs stimulate my cardiovascular and muscular system to stay healthy. To get faster there are times I have to run 8 miles in an hour or do speed work on a track. The amount of stimulus that these provide to my cardiovascular system and muscular system are much greater. So after these workouts I hurt a lot more, but again the soreness may go away in a few hours today. If I, however, run as fast as I can for 13.1 miles (half marathon) or an ultramarathon (50 miles) then you can bet I will be sore for a week! So if every week I ran a half marathon as fast as I could, soon I would be injured.
When a person receives Prolotherapy once per month with hypertonic dextrose, published Prolotherapy research from our office confirms that patients with degenerative arthritis of the knees (for instance) regain their ability to exercise and walk because the crepitation (crunching) and pain in their knees is significantly less after Prolotherapy treatments. The patients also notice that their range of motion is improved. We therefore assume that the degenerative process is reversing inside the body. In other words, the hypertonic dextrose solution acts like a 7 or 8 mile run in an hour. It isn’t acting like a 50 mile ultramarathon. If the person was to receive Prolotherapy every hour or for that matter every day, at some point the body would say “enough is enough.” But this is not how Prolotherapy is done. It is typically performed every four to six weeks.
Stem cell Prolotherapy combined with dextrose Prolotherapy.
Some of our patients receive stem cell Prolotherapy in conjunction with traditional dextrose Prolotherapy. We obtain the stem cells from the patients’ own bone marrow or fat, process them, and then inject them into the injured joint(s) in cases of more severe degeneration or injury/tears. We find that in most cases, the injury is accompanied by an overriding joint instability, so not only do we inject inside the joint (with the stem cells) but around the joint as well, using dextrose Prolotherapy to repair these loosened ligaments and tendons. When stem cell Prolotherapy is given, not only are thousands of stem cells injected into the joint, but also the growth factors that help support them. The growth factors are derived either from the bone marrow itself or from platelet rich plasma (Note: PRP or bone marrow may be utilized to obtain the growth factors). These solutions contain plenty of dextrose (glucose) naturally, so no additional dextrose is given. In other words, when utilizing stem cell Prolotherapy, the dextrose Prolotherapy is given to the structures outside the joint, such as the ligaments or tendons. The dextrose is not injected into the joint when stem cells are utilized because we want the maximum amount of stem cells and growth factors injected into the joint (i.e. not to utilize some of the space for dextrose, because it is naturally contained in the bone marrow or PRP solution). This combination approach works exceedingly well to return our patients to full function.
Summary of stem cell proliferation and dextrose.
In summary, hypertonic dextrose in published studies helps stem cell proliferation in vitro (in cultures.) While this is important, more important is what it does in the human body. I have written a systematic review of the numerous studies performed around the world using hypertonic dextrose Prolotherapy (publication pending) and I feel the results speak for themselves. Dextrose Prolotherapy in published study after published study has been shown to be extremely effective at eliminating or reducing a myriad of chronic painful conditions including degenerative arthritis. For this reason, dextrose Prolotherapy should be the treatment of choice for the resolution of chronic pain. When combined with stem cell Prolotherapy, dextrose Prolotherapy can be an even more powerful tool for more severe cases of degeneration, knowing that the dextrose itself assists with the proliferative healing process.
1Heywood HK, Bader DL. Glucose Concentration and Medium Volume Influence Cell Viability and Glucosaminoglycan Synthesis in Chondrocyte-Seeded Alginate Constructs. Tissue Engineering. 2006;12:3487-3496.
2Mischen BT, Follmar KE. Metabolic and Functional Characterization of Human Adipose-Derived Stem Cells in Tissue Engineering. Plastic & Reconstructive Surgery. 2008;122:725-738.
3Deorosan B, Nauman EA. The Role of Glucose, Serum, and Three-Dimensional Cell Culture on the Metabolism of Bone Marrow-Derived Mesenchymal Stem Cells. Stem Cell International. 2011; Article ID 429187, 12 pages. Doi:10.4061/2011/429187