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 Injections Reduce Lower Back Pain

W. Jeremy Beckworth and his co-workers at Emory Orthopaedics and Spine Center, in collaboration with several other orthopedic care groups, have participated in a clinical trial that demonstrated that a single injection of stem cells into degenerative intervertebral discs significantly reduced lower back pain for at least 12 months according. Beckworth’s clinical trial consisted of 100-patients and was a phase II, international clinical trial.

Beckworth, assistant professor of Orthopaedics and Rehab Medicine, gave patient injections of a subset of mesenchymal stem cells isolated from bone marrow stem cells called mesenchymal precursor cells (MPCs) in order to attenuate pain in patients with lower back pain. On average, Beckworth and his colleagues discovered that stem cell injections led to a reduction in pain levels greater than 50 percent at 12 months. Additionally, patients who received stem cell injections felt less of a need for pain medications, showed an improvement in function, and less need for further surgical and non-surgical spine interventions. These results were compiled from patients with moderate to severe disc-related lower back pain.

“These are very exciting findings,” explains Beckworth. “The results provide significant hope for a condition that has been very tough to treat. Discogenic low back pain, a painful degenerative disc, is the most common cause of chronic low back pain.”

This phase II clinical trial builds on a previously reported preclinical study showed that highly purified MPCs were able to repair and restore disc structure. All the data from this trial showed that there were statistically significant improvements in patients who received stem cell injections compared to those in control groups who received no such injections.

“Currently there is no adequate treatment for discogenic low back pain,” says Beckworth. “Both conservative and surgical treatments fall short. These positive results pave the way for a phase III study that may be starting later this year.”