New Way to Counter Spinal Disc Degeneration
Cedars-Sinai investigators have been able to prevent degeneration of spinal discs in laboratory animals with a new approach that uses stem cell technology.
A new study by Cedars-Sinai investigators could ultimately lead to better treatments for lower back pain.
The study was recently published in the journal Theranostics. If confirmed in people, the study's findings could point to a potential way to treat back pain that is related to degenerative disc disease, which occurs when the discs between the vertebrae of the spinal column deteriorate or break down. Lower back pain in particular affects many adults and is a frequent cause of disability. It is one of the major clinical and socioeconomic global health burdens.
Despite decades of research, most existing therapies for degenerative disc disease treat the symptoms rather than the causes, said Dmitriy Sheyn, PhD, who heads a laboratory focusing on orthopedic stem cell research at the Cedars-Sinai Board of Governors Regenerative Medicine Institute.
Dmitriy Sheyn, PhD
"There is an urgent need for an alternative treatment such as stem cell therapy, which is focused on correcting the underlying pathogenesis of disc disease," said Sheyn, an assistant professor of Orthopaedics, Surgery and Biomedical Sciences. He was co-corresponding author of the study.
The study team's approach focuses on notochordal cells, which are responsible for the formation and maintenance of spinal discs. These cells eventually may be lost in adolescence. Previous studies have associated dwindling numbers of notochordal cells with degenerative disc disease.
Replacing notochordal cells is a challenge, explained Zulma Gazit, PhD, associate professor of Surgery and co-director of the Skeletal Regeneration and Stem Cell Therapy Program at the institute. "We lack an appropriate cell source — one that can be compatible with the harsh environment in which these cells live, yet is safe and sufficiently available," said Gazit, senior author of the study.
Zulma Gazit, PhD
To solve this problem, the study team first took small samples of dermal fibroblasts— the cells that form the skin's connective tissue and perform repairs—from human subjects. Using stem cell technology, they transformed these cells into induced pluripotent stem cells (iPSCs), which can multiply rapidly and morph into different, specialized types of cells.
By exposing these iPSCs to a protein modifier and encapsulating them in a hydrogel that simulated the spinal disc environment, the cells began to mimic notochordal cells. The team used these manufactured cells to treat laboratory pigs that had induced spinal disc degeneration.
After eight weeks, examination of the spinal discs of the treated subjects showed that they appeared to have been protected from further degeneration. The pH level of the discs, an indicator of healthy tissues, also was close to a normal level. In an additional experiment, the engineered cells were injected into immune-compromised laboratory mice to demonstrate that the cells did not induce tumors as a side effect.
"Restoration of disc function and prevention of degeneration remain the ultimate goals of current research," Sheyn said. "In this study, we showed a way to generate functioning notochordal cells from pluripotent cells that have a functional protective and regenerative effect without causing side effects or introducing safety concerns. This outcome has real potential for being the next cell therapy for intervertebral disc degeneration."
Funding: Research reported in this publication was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under award numbers R01AR066517 and K01AR071512 and by the California Institute for Regenerative Medicine (DISC1-10643).