Stem Cell Prolotherapy effective in halting and reversing degenerative disc disease

Prolotherapy Knee articular cartilage repair without surgery

Ross Hauser, MD

The excitement surrounding stem cells for degenerative disc disease is in its ability to change a degenerative disc disease environment into a healing and regenerative environment. In other words biological healing and not rods, screws, and hardware found in spinal surgical procedures.

We are going to look at a few landmark scientific papers that provide a fascinating look into the degenerative disc environment. These research papers will show how incredible the interaction of stem cells and the microenvironment of the disc is and how this interaction can produce degeneration and how it can produce regeneration and help patients avoid the need for surgery.

If you are exploring stem cells as a possible treatment for your degenerative disc disease, we will also show research on how Stem Cell Prolotherapy can be a non-surgical option to repair the damage in your spine.

This first study we will explore comes from researchers at Vrije Universiteit in the Netherlands. It appears in the medical journal Osteoarthritis and Cartilage, (July 2015).  The simple purpose of this paper was to understand how degenerative disc disease began and how it progressed. The researchers looked for answers in mechanical breakdown (mechanical breakdown is pain with movement) and they looked for answers in micro-environment breakdown (what is happening at the cellular level).(1)

Before we look into this research, first an explanatory note on the nucleus pulposus.

The nucleus pulposus is the inner spongy core of the disc. It is a composition of water and collagen fibers. Like a sponge, it is larger when hydrated, providing a spongy cushion for the stress and demands of spinal movement. When the nucleus pulposus flattens out, develops cracks and fissions, loses its water, or bulges, the spongy cushion of the disc no longer protects against degenerative disease. The disc itself develops cracks and fissions, damage to the vertebra begins in the form of bony disintegration and the formation of bone spurs.

Now let’s look at the research from the Netherlands.

Disc inflammation

From the research: In the degenerating intervertebral disc, there is a progressive increase in the expression of inflammatory cytokines. These cytokines, expressed by nucleus cells, up-regulate matrix remodelling involved in intervertebral disc degeneration.

What does this mean?

The immune system recognizes damage is occurring in the discs. The expression of inflammatory cytokines is the response of the immune system’s signalling system that is changing the disc environment towards degeneration by bringing more inflammation to the area than the area can handle. As the degeneration progresses inflammatory cytokines upregulates or sensitizes, or even over-sensitizes the pain response.

The Dr. Jekyll/Mr. Hyde characteristics of collagen and water – bad hydration

To make a simple analogy, if it is a hot day and you are active, water is the best drink. You should not consider drinking equal amounts of wine. The wine will dehydrate you further. This is what is happening in your back. In the microenvirnment the wrong hydration is occurring.

From the research: The nucleus pulposus extracellular matrix consists of proteoglycans and collagens, and aggrecan is by far the most abundant proteoglycan in the nucleus.

In other words, the cells of the disc jelly lay in a pool of their own extracellular matrix. That matrix is converted into building blocks to repair damage. Aggrecan is a proteoglycan, a building block protein in that pool water. It helps make Collagen Type 2 which is the stuff of cartilage.

Back to the research: (In a diseased environment)  the biochemical content of the extracellular matrix changes from predominantly proteoglycans and collagen type II to a more fibrous tissue consisting primarily of collagen type I, resulting in a loss of water-binding potential.

In other words, Collagen is acting as the infamous Dr. Jekyll/Mr. Hyde character, it is good for us, it is very bad for us. While Collagen Type 2 is elastic and protecting of the discs, Collagen Type 1 is not. Collagen Type 1 is the stuff of scar tissue. It goes to the sites of wounds where the normal immune repair function cannot fix the injury. It fortifies the site with hard, inflexible tissue. Hard tissue does not absorb water as well as soft tissue.

Spinal pressure, stress and a flattened disc

If you were to lay a can of tomato sauce on its side and press down on the can with your hands, you will likely not be strong enough to crush the can. If you were to open the can, take out all the tomato sauce, put it on its side again and press down, you will be able to crush the can.

The difference is the shift of hydrostatic pressure to shear stresses in a degenerative disc environment.

Hydrostatic pressure, that is the force of the tomato sauce inside the can on the can walls, keeps the can from being crushed. Shear stresses applied without the tomato sauce in the can crushes the can. So as it happens to your disc.

Back to the research: The shift of hydrostatic pressure to shear stresses in the intervertebral disc has a distinct mechanobiological effect on the nuclear chondrocytes. . . the increase in shear stress will initiate the formation of a fibrous tissue, rich in collagen type I. 

You are making scar tissue to repair the damage, Collagen Type 1.

Furthermore, increased shear stress increases the production of nitric oxide by chondrocytes. Nitric oxide is a reactive oxygen metabolite that reduces proteoglycan production, and increases apoptosis in cartilage and in the intervertebral disc.

What does this mean? Nitric Oxide is another of our body’s Dr. Jeykll/Mr. Hyde molecules. In a normal joint environment, nitric oxide regulates inflammation as a healing agent. In an abnormal toxic non-healing joint environment, nitric oxide production gets stuck in the  “open,” position creating chronic damaging inflammation. Apoptosis in cartilage and in the intervertebral disc. 

Apoptosis is death, your disc is dying.

As we can see from this research degenerative disc disease is so much more than a bulging disc that rods, screws and hardware can fix. It is a whole joint disease.

Can stem cells heal degenerative disc disease?

Stem cell Prolotherapy or stem cell therapy are injection techniques. They are explained in this video.


Injections directly into the disc or around the disc?

Researchers are suggesting that eventually direct injection of stem cells or platelet rich plasma into the disc may be the answer. Some doctors are exploring this treatment now as we are investigating the potential of intra-disc injections.

Research, including a “landmark study,” from the Mayo Clinic in the medical journal Gene, suggests that stem cell therapy, the inection directly into the disc, can be a viable and effective treatment in halting or reversing degenerative disc disease of the spine.2

Doctors in Italy writing in the August 2017 edition of Musculoskeletal surgery suggest:

“Regenerative medicine, such as the use of mesenchymal stem cells or platelet-rich plasma, in intradiscal disc degeneration has shown preclinical and clinical positive results. Randomized clinical trials studying the potential of mesenchymal stem cells intradiscal injection have not been conducted, and PRP effect has been studied only preliminarily. Additional more powered high-quality studies are needed to really appreciate the long-term safety and efficacy of regenerative medicine approaches in IDD.”3

Fair enough, we are research the benefits as well.

How do intradiscal injection of stem cells heal degenerative disc disease? Doctors in Portugal writing in Stem cells translational medicine, offered their rationale and some intriguing findings. Let’s review their study.

In this research the focus is on the diseased disc environment, one that is hostile to disc regeneration. So injecting stem cells directly into the disc may not be as productive as hoped.

So the researchers went about another way. They explored giving the stem cells intravenously in test animals and relied on the body to use cell signalling to get the stem cells to the site of the disc damage.

By not directly injecting the stem cells into the disc, the intravenous delivery method provided a way to get stem cells where they needed to be and allowed the stem cells to chose that place where they could best do their work.

Comment: You cannot heal the problems of a flattened disc without addressing the problems of what caused the flattened disc and how the disc sits in its current diseased environment. 

To patch the hole in this “disc,” you must first stabilize the truck and fix the high mechanical stress and pressure on the disc.  Applying a patch to the hole and forcing air into it to re-inflate it is may not be the best plan.

In the research we are discussing, the indirect application of stem cells, by way of experimental intravenous, is somewhat similar to injecting Prolotherapy, PPR, or stem cells around the disc. It provided the means to stabilize the area so repair could begin in a less hostile environment.

This is the whole spine dynamic of spinal instability. 

The discussion on spinal instability and treatment is as complex as the subject itself. We address this subject in numerous articles on our Caring Medical website.

Cell signalling and disc repair

Cell signalling is perhaps the most fascinating feature of stem cell therapy. When stem cells are introduced into a new location one of the first things they do is set up a communication network (signalling through chemical expression). Then they create a  blue print for repair and provide directions to the growth and healing factors within themselves, the native stem cells and the local inflammatory mechanism. Please see The Paracrine Effect and Inflammation in our article on Stem cell therapy for bone repair in osteoarthritis.

But the Portuguese team found something even more remarkable – the mechanisms which the stem cells began to change the disc disease environment into a healing disc environment.

The stem cells were able to:

The researchers could only conclude that their research highlighted the complex interplay between stem cells and cells of the immune system in achieving successful tissue regeneration in degenerative disc repair.4

More articles from our website.


If you have questions about degenerative disc disease, You can get help and information from our Caring Medical staff

1 Vergroesen PP, Kingma I, Emanuel KS, Hoogendoorn RJ, Welting TJ, van Royen BJ, van Dieën JH, Smit TH. Mechanics and biology in intervertebral disc degeneration: a vicious circle. Osteoarthritis and Cartilage. 2015 Jul 31;23(7):1057-70.

2 Wang Z, Perez-Terzic CM, Smith J, et al. Efficacy of intervertebral disc regeneration with stem cells – A systematic review and meta-analysis of animal controlled trials. Gene. 2015 Jun 10;564(1):1-8. doi: 10.1016/j.gene.2015.03.022. Epub 2015 Mar 19.

3 Basso M, Cavagnaro L, Zanirato A, Divano S, Formica C, Formica M, Felli L. What is the clinical evidence on regenerative medicine in intervertebral disc degeneration?. Musculoskeletal surgery. 2017 Feb 13:1-2.

4 Cunha C, Almeida CR, Almeida MI, Silva AM, Molinos M, Lamas S, Pereira CL, Teixeira GQ, Monteiro AT, Santos SG, Gonçalves RM, Barbosa MA. Systemic Delivery of Bone Marrow Mesenchymal Stem Cells for In Situ Intervertebral Disc Regeneration. Stem Cells Transl Med. 2016 Oct 11.


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