Mesenchymal Stem Cells Reduce Scarring of Intervertebral Discs and Facilitate Healing


Intervertebral disc degeneration causes substantial back pain and associated pain that shoots down the legs (radiculopathy). Back issues associated with bad intervertebral discs are a leading cause of disability. Such disability costs employers millions of dollars of lost man and woman power and employees extensive loss of wages. Chronic back pain can also seriously compromise the quality of life and presents a large societal burden.

To date, surgery is the only effective treatment option, but surgical interventions sometimes leave patients worse off than before. Thus there is presently no effective intervention for this disease.

However, in a recent paper, Victor Y.L. Leung and his colleagues from the University of Hong Kong and several other institutions as well have used human mesenchymal stem cells from bone marrow to treat damaged intervertebral discs in rabbits. The results, published in the journal Stem Cells, are quite hopeful

Leung and others discovered that by puncturing the intervertebral discs of rabbits with a syringe needle, they could induce damage to the disc that mimics disc degeneration in humans.

Next, they implanted human bone marrow-derived mesenchymal stem cells (MSCs) into the damaged discs. Such implantations prevented scarring of the disc in the center of the disc. The center of the disc, the nucleus pulposus, is more gel-like than the surrounding annulus fibrosus. Scarring of the nucleus pulposus stiffens it and prevents it from moving with stress. An inability to bend with stress causes the disc to become brittle with time and herniate. However, implantation of mesenchymal stem cells preserved the mechanical properties of the disc and benefitted overall spinal function.

By looking more deeply at the mechanism by which mesenchymal stem cells preserve disc function, Leung and others showed that MSCs suppress abnormal deposition of collagen I in the nucleus pulposus. Since collagen is made during scarring, suppression of collagen I synthesis suppressed scarring. Secondly, implanted MSCs decreased the expression of two molecules that promote the synthesis of collagen I. By suppressing the expression of MMP12 and HSP47, the implanted MSCs also reduced collagen aggregation and maintained the microarchitecture of the disc and its mechanical properties.

This  study supports the ability of MSCs to stimulate resident stem cell activities and disc healing. The implanted MSCs seem to do so by means of down-regulating collagen  fibril formation. This provides the basis for the MSC‐based disc therapies.

Stem Cell Treatment for Degenerative Disc Disease


A new analysis of stem cell trials that targeted degenerative disc disease of the spine in animals has shown that these treatments are effective in halting or even reversing this disease. Such results should facilitate the implementation of human clinical trials.

Our spinal cords are encased in a protective body of bone known as the vertebral column. The vertebral column consists of a stack of vertebral bodies that are positioned with one vertebra one on top of the other. Between each pair of vertebral bodies is a cushion-like structure known as the intervertebral disc. The intervertebral disc absorbs the stress and shock placed on the vertebral column when someone walks, runs, moves, bends, or twists. The discs prevent the vertebral bodies from grinding against each other.

Vertebral column

Structurally, the intervertebral discs are unique. They have no blood supply of their own, and are, as a matter of fact, the largest structures in the body without their own blood vessel system. Instead they absorb the nutrients they need from circulating blood by means of osmosis.

Each intervertebral disc is composed of two parts: an outer annulus fibrosus (fibrous ring) and the nucleus pulposus (pulpy interior). The annulus fibrosus is a ring-like structure that completely encases the nucleus pulposus. It is composed of water and strong elastic collagen fibers bound together by glue-like material called proteoglycan. The arrangement of these collagen fibers at varying angles relative to each other makes the annulus fibrosus a rather strong structure. The annulus fibrous stabilizes the intervertebral disc and helps the spine can rotate properly and resist compression or other stresses placed on the spine.

The center portion of the intervertebral disc that is protected by the annulus fibrosus is a gel-like elastic substance called nucleus pulposus. The nucleus pulposus transmits and transfers stress and weight placed on vertebrae during movement and activity. The nucleus pulposus is made of the same basic materials as the nucleus fibrosus: water, collagen, and proteoglycans. The main difference between the ring-like annulus fibrosus and the gel-like nucleus pulposus is the relative amounts of these substances. The nucleus pulposus contains more water than the annulus fibrosus.

Intervertebral disc structure

Recent developments in stem cell research have made it possible to measure the effects of stem cells treatments on intervertebral disc height. Researchers at the Mayo Clinic in Rochester, Minnesota have pioneered such techniques.

In preclinical animal studies, stem cell treatments have been used to treat animals with degenerative disc disease. Because degenerative disc disease can great affect someone’s quality of life and productivity, such a treatment has been highly sought after.

Wenchun Qu, MD, PhD, of the Mayo Clinic in Rochester, Minn said that stem cell injections into degenerating intervertebral discs not only increased disc height, but also increased disc water content and improved the expressed of particular genes. “These exciting developments place us in a position to prepare for translation of stem cell therapy for degenerative disc disease into clinical trials,” said Qu.

Animals that had received stem cell injections into their intervertebral discs had a disc structure that was large restored. The nucleus pulposus showed an increased water content and improved abilities to transfer shear forces.

In their analysis, Qu and his colleagues examined six preclinical trials and only examined those studies that were randomized and properly controlled. Because of various methodological differences between these studies, Qu and his gang used a random-effects model to analyze the data. Random-effects models, put simply, put all the animals in a group of studies together and assumes that they can be placed in a hierarchy of those who are the sickest to those who are the least sick. By placing the individuals in a hierarchy like this they can be classified accordingly and the effects of their treatments assessed fairly.

When properly and rigorously analyzed, the intervertebral disc height increases were significant in all six studies.  What they found was an over 23.6% increase in the disc height index in the transplant group compared with the placebo group (95% confidence interval [CI], 19.7-23.5; p < 0.001). None of the 6 studies showed a decrease of the disc height index in the transplant group. Increases in the disc height index were statistically significant in all individual studies.

On the strength of these preclinical studies, Qu and his colleagues think that it is time to determine the safety, feasibility, and efficacy of stem cell transplants for degenerative disc disease in human patients.

Because intervertebral discs show such poor regenerative capabilities, degenerative disc disease is an excellent candidate for stem cell treatments. Also, present treatments tend to be very invasive and often make the disc worse.