Washington DC [US], September 29 (ANI): Scientists have discovered a stem cell that appears to serve as a master source for tendon and ligament cells throughout the body.
In lumbar spinal stenosis, these cells become unusually active and may drive the ligament overgrowth that squeezes spinal nerves and causes pain, numbness, and difficulty walking. Researchers found that reducing calcium signaling stopped this abnormal growth in mice.
Researchers at Weill Cornell Medicine and Hospital for Special Surgery have identified a previously elusive population of stem cells that appears to produce the body’s tendons and ligaments, the connective tissues that link muscles and bones.
The scientists also found evidence that these cells can become overactive in the lower spine, where they may contribute to lumbar spinal stenosis. The condition affects an estimated 103 million people worldwide and develops when thickened ligaments reduce space inside the spinal canal. This narrowing can put pressure on nerves and lead to pain, numbness and difficulty walking, according to the ScienceDaily website.
The study, published Sept. 7 in Cell, raises the possibility that targeting these stem cells could eventually lead to new treatments for spinal stenosis. One potential approach may involve drugs already used to control high blood pressure.
“While previous studies had proposed several candidate stem cells, none had definitively shown that a single cell population could both self-renew and generate the full spectrum of tendon and ligament cell types,” said co-corresponding author Dr. Matthew Greenblatt, the Rohr Family Research Scholar, associate professor of pathology and laboratory medicine at Weill Cornell and a pathologist at NewYork-Presbyterian/Weill Cornell Medical Center, as quoted by ScienceDaily website.
After identifying the cells, the team investigated whether they might offer clues to treating lumbar spinal stenosis, particularly for patients who currently have few options other than surgery once the condition becomes severe.
“Identifying these specialized stem cells unlocks a new area of research that allows us to address this disease much more mechanistically, rather than just waiting until a patient’s condition worsens and requires surgery to relieve the nerve compression,” said study co-corresponding author Dr. Sravisht Iyer, an associate professor of orthopedics at Weill Cornell and a spine surgeon at Hospital for Special Surgery (HSS).
“The findings are exciting for their potential to change the way we deliver spinal care,” added Iyer as quoted by the website.
Finding the Stem Cells That Build Tendons and Ligaments
Dr. Greenblatt and his colleagues had previously tracked down several important skeletal stem cell populations. In 2018, the group identified the stem cell that begins fracture repair in the outer layer of bone. They later discovered stem cells involved in forming the skull and spine.
Finding an equivalent cell for tendons and ligaments proved more difficult. Unlike bone, these tissues contain many fibroblast-like cells that look similar, making it challenging to distinguish one cell population from another.
“We analyzed thousands of individual cells and sorted them into individual cell types. Then we identified which one had the properties we associate with ‘stemness,'” said Dr. Greenblatt.
In this case, “stemness” refers to the ability of a rare cell population to continually renew itself while also producing the mature cells required to form and maintain tendon and ligament tissue. In mice, the researchers found these cells living in a specialized region inside tendons and ligaments that appears to act as a reservoir for tissue growth and repair.
The team then used what it had learned from mice to search for similar cells in people. Human ligament samples came from tissue removed by Dr. Iyer during surgery from patients who had provided informed consent.
The researchers, including first author Dr. Lingling Hu, a postdoctoral fellow in Dr. Greenblatt’s and Dr. Iyer’s labs, confirmed that the human cells could both renew themselves and generate ligament cells.
The cells also appeared to exist far beyond the spine.
“We looked in the kneecap ligament; we looked at the Achilles tendon; and everywhere we looked, we found this cell,” said Dr. Greenblatt. “So, we think this is the universal stem cell for tendons and ligaments throughout the body.”
How Stem Cells May Contribute to Spinal Stenosis
The researchers next examined whether these cells could be involved in lumbar spinal stenosis.
They compared stem cells taken from patients with spinal stenosis with cells collected from spinal ligaments removed from people who had herniated discs but showed no signs of stenosis. The patients provided informed consent pre-operatively.
Ligaments from people with stenosis contained more of the newly identified stem cells. When the researchers transplanted those cells into mice, they produced more tendon cells than stem cells taken from people without stenosis.
“Though spinal stenosis is a complex condition, this really showed us that these cells are contributing to the pathology,” said Dr. Greenblatt, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell.
The researchers then looked more closely at what was happening inside the cells. Stem cells associated with stenosis showed greater calcium signaling than healthy cells.
Calcium signaling is one of the ways cells communicate internally and control processes such as growth and activity. When the scientists genetically increased calcium signaling in stem cells from healthy ligaments, they were able to trigger excessive tissue growth.
A Possible Drug Target for Spinal Stenosis
The opposite effect was also important. When the researchers reduced calcium signaling in a mouse model of lumbar spinal stenosis, abnormal cell growth was blocked.
That finding suggests calcium signaling could become a therapeutic target. It also raises the possibility that calcium channel blockers, a class of drugs already widely used to treat high blood pressure, could one day be studied as a treatment for spinal stenosis. Clinical trials will be needed before researchers can determine whether this approach is safe or effective in patients.
“This is probably the first work that’s shown a potential therapeutic target for one of the most common spine conditions in the world,” said Dr. Iyer.
The implications may extend beyond spinal stenosis. Dr. Greenblatt plans to investigate whether the same stem cells are involved in other connective tissue conditions, including Marfan syndrome, a genetic disorder that affects connective tissues throughout the body, according to the website.
The discovery could also help researchers better understand why some tendon and ligament injuries are so difficult to heal. Potential areas of future study include rotator cuff tears, Achilles tendon injuries, ligament reconstruction and chronic tendon degeneration.
“Given that this cell appears to be the ultimate origin of all tendon and ligament cells, defects in this cell are likely at the heart of a wide range of tendon and ligament disorders,” said Dr. Greenblatt. (ANI)
