Cedars-Sinai investigators have uncovered new insight into the developmental process of the intervertebral disc that could help lead to the advancement of more targeted treatments for back pain.

Using single-cell RNA-sequencing technology, the team identified two previously unknown populations of notochordal cells in adults that were previously believed to disappear in childhood. These cells are precursors of the intervertebral disc—a shock-absorbing structure that provides the flexibility and mobility of the spine—and can be used as novel markers to help identify different subtypes of cells in the tissue.

The findings are published in the peer-reviewed journal iScience, published by Cell Press.

"This study provides the first comparison of cell atlases at single-cell level between neonatal and adult intervertebral disc cells," said Dmitriy Sheyn, PhD, co-senior author of the study and an assistant professor in the departments of Orthopaedics, Surgery and Biomedical Sciences at Cedars-Sinai. "Understanding the cellular landscape and the heterogenicity of the intervertebral disc and development processes will help our efforts to regenerate the disc and develop therapeutics for lower back pain."

Lower back pain is one of the most common conditions that eventually lead to surgical interventions, chronic pain and use of opioids in the United States. At least 80% of the adult population is suffering from lower back pain, 40% of which originates in intervertebral disc degeneration. Once degeneration cascade starts, it is very difficult to slow it down or reverse it.

To date, most treatments for intervertebral disc degeneration are limited to invasive surgery interventions, such as disc replacement and spinal fusion, or pain management that does not address the underlying cause of intervertebral disc degeneration. 

Researchers in the Board of Governors Regenerative Medicine Institute at Cedars-Sinai are looking to develop stem cell therapies for intervertebral disc degeneration that will help reduce chronic pain and prevent invasive surgery and overuse of pain medications.

To better understand this chronic condition, researchers compared the cellular composition of the intervertebral disc of an adult with the intervertebral disc of a neonate. 

This was made possible by using single-cell technology and through a collaboration with co-senior author of the study Ritchie Ho, PhD, an assistant professor of Biomedical Sciences and Neurology in the Regenerative Medicine Institute and an expert in single-cell sequencing. 

Unlike most organs, the development of the musculoskeletal system starts in the fetus but continues after birth and during childhood. By knowing the cellular composition of a developing tissue, researchers can better understand how it can also rejuvenate itself with aging and regenerate itself after injury. 

"This is the first step that will allow us to characterize the subtypes of cells discovered in the intervertebral disc and study in depth their function in development, homeostasis and regeneration of the tissue," said Wensen Jiang, PhD, the first author of the study.

In the analysis, the team found a population of notochordal cells in a 70-year-old adult, which was surprising to the team since notochordal cells were believed to completely disappear in the human intervertebral disc by around the age of 10.

"The fact that notochordal cells can survive for 70 years in the intervertebral disc gives us hope for future stem cell therapies," said Sheyn. 

With this new understanding, the team will start looking at healthy intervertebral disc compositions in newborns and adults to analyze the differences between the degenerated asymptomatic intervertebral discs and degenerated intervertebral discs that induce chronic back pain as well as the role specific cell subtypes play in the mechanism of disease onset and progression.

Other Cedars-Sinai authors in this study include Juliane Glaeser, Khosrowdad Salehi, Giselle Kaneda, Pranav Mathkar and Anton Wagner. 

Research for this study was supported in part by a career development award from the National Institutes of Health.