Caring Medical - Where the world comes for ProlotherapyIs there evidence that direct stem cell injections into degenerated discs can reverse degenerative disc disease?

Ross Hauser, MD  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
David N. Woznica, MD | Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois
Katherine L. Worsnick, MPAS, PA-C  | Caring Medical Regenerative Medicine Clinics, Fort Myers, Florida
Danielle R. Steilen-Matias, MMS, PA-C | Caring Medical Regenerative Medicine Clinics, Oak Park, Illinois

Is there evidence that direct stem cell injections into degenerated discs can reverse degenerative disc disease?

One of the most confusing aspects of stem cell therapy is the question: “do you inject stem cells directly into the flattened disc?” In our practice, that answer is no. We will explain why below with supportive research and the empirical evidence of more than 26 years experience in offering spinal injections on what we consider the best way and best evidence for stem cell therapy for degenerative disc disease.

It is easy for patients to get excited about the prospect of stem cell therapy for their back pain. If you are reading this article you are likely one of those people who are “tired of the patches, tired of the pain medications, and tired of the pain.” You are also likely one of those people who had a spinal procedure that did not offer you the hoped for or wished for results you were seeking or you are someone who has steadfastly refused spinal surgery for your own reasons. You may have decided to avoid surgery because while you were sitting in the waiting room of the surgeons office you had a chance to talk to some patients who had procedures. To be fair, spinal surgery does help a lot of people. It is the ones who surgery who can’t help or did not help are the ones we see.

Research: Stem cells do not pump up deflated discs directly. They work in a different way.

Before we begin this section we do want to point out that we do not offer or suggest stem cell therapy to every patient with back pain. In fact we offer stem cell therapy to very few patients with a long history of back pain. Why? Because problems of degenerative disc disease are problems that have developed over long periods of time. The problems of degenerative disc disease find their origins, not is a flat, bulging, or herniated disc, but in problems of spinal instability caused by weakened spinal ligaments. The disc is the end result of this degenerative damage. To fix the disc problem, you must fix the instability problem.

Comment: You cannot heal the problems of a flattened disc without addressing the problems of what caused the flattened disc – spinal instability

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 is only a fix, not a solution, the disc will go flat again.

Because we have found that Prolotherapy, dextrose injections not stem cells, in combination with Platelet Rich Plasma Therapy (PRP) (your blood platelets not stem cells), are as effective and are a less costly procedure for many patients in reversing and repairing the problems instability, we often suggest this route first. This is explained in detailed in these articles: The evidence for an alternative to Spinal fusion surgery – Spinal ligament repair injections, Prolotherapy non-surgical treatment of a bulging or herniated disc, and Spondylolisthesis,  Spondylolysis, Spondylisis. A problem of disc degeneration or ligament degeneration?

We do use stem cell therapy when the situation warrants its usage.

Make no mistake, there is an excitement in the medical community  surrounding stem cell use for degenerative disc disease. The excitement surrounds stem cells ability to change a degenerative disc disease environment into a healing and regenerative environment. In other words, the stem cells are acting upon your immune system to begin a new healing process in your spine.

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 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.

When you are thinking stem cells, your must understand back pain at a cellular level

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).(1)  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).

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 and flat when dehydrated. The disc’s purpose is to provide 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 acts in its role as spinal stabilizer. Spinal instability begins as does the formation of bone spurs in the spine and problems related to stenosis.

Progression of Degeneration of Lower Back
The disc becomes inflamed

The research team continued with their observations with this explanation of the development of disc inflammation: 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.

Disc inflammation, What does this mean? More inflammation in the spine than the spine can handle.

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. What does this mean? It is an explanation for your back pain.

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.

Now that we understand what is happening inside the disc we can now explain why we do not inject directly into 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 not convinced. As we do not directly inject into the disc we want to explain the research that gives a counter suggestion.

Research, including a “landmark study,” from the Mayo Clinic in the medical journal Gene, suggests that stem cell therapy, the injection directly into the disc, can be a viable and effective treatment in halting or reversing degenerative disc disease of the spine in four-legged animals but a conclusion was not reached on 2 legged humans.(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 researching the benefits as well.

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

Prolotherapy Specialists degenerative disc disease
Danielle Steilen-Matias, PA-C | Katherine Worsnick, PA-C | Ross Hauser, MD | David Woznica, MD

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. [Google Scholar]

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. [Google Scholar]

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. [Google Scholar]

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