Researchers at Weill Cornell Medicine and the Hospital for Special Surgery say they've identified the specific stem cell responsible for the ligament overgrowth that causes lumbar spinal stenosis, a narrowing of the lower spine that affects an estimated 103 million people worldwide and is a leading cause of pain and difficulty walking in older adults.
The condition develops when the ligaments running along the spinal canal thicken and encroach on the space meant for nerves, producing pain, numbness and, in severe cases, trouble walking. Until now, doctors had few options beyond physical therapy, injections or surgery to physically remove the excess tissue — there was no drug that targeted the underlying biology.
In a study published in the journal Cell, the team — led by first author Lingling Hu alongside senior researchers Matthew Greenblatt and Sravisht Iyer — sorted thousands of individual cells from mouse and human tendon and ligament tissue to track down a stem cell population responsible for generating and repairing those tissues. Comparing ligament samples removed during surgery from patients with and without spinal stenosis, they found stenosis-affected tissue contained more of these stem cells, and that the cells showed unusually high calcium-signaling activity.
When the team raised calcium signaling in healthy stem cells, it triggered the same kind of tissue overgrowth seen in stenosis patients. Dialing the signaling back down in a mouse model of the disease blocked the overgrowth — giving them a mechanism, and potentially a target already addressed by an existing class of medication.
"This is probably the first work that's shown a potential therapeutic target for one of the most common spine conditions."
Sravisht Iyer, Weill Cornell Medicine and HSS
"Defects in this cell are likely at the heart of a wide range of tendon and ligament disorders."
Matthew Greenblatt, Weill Cornell Medicine
From Mice to a Possible Pill
Because calcium channel blockers — a decades-old class of drugs already prescribed for high blood pressure — can dial down the same signaling pathway, the researchers say repurposing them is a plausible next step. But that remains speculative: the calcium-lowering experiments were done in mice and isolated cells, not in people with stenosis, and no clinical trial has tested whether an existing blood pressure drug can shrink overgrown spinal ligaments or relieve symptoms. The team, described in coverage from the Hospital for Special Surgery, says it next wants to test that idea directly, and to explore whether the same stem cell malfunctions contribute to other tendon and ligament problems, including Marfan syndrome and chronic tendon injuries that heal poorly.