Researchers at Weill Cornell Medicine and Hospital for Special Surgery have discovered the unspecialized stem cells that give rise to the body\u2019s tendons and ligaments, the tissues connecting muscles and bones. They also found that when these stem cells become hyperactive in the lower spine, they contribute to lumbar spinal stenosis. This condition, which impacts an estimated 103 million people worldwide, involves enlarged ligaments that can narrow the spinal canal and compress nerves, causing pain, numbness and difficulty walking.<\/p>\n
The study, published Sept. 7 in Cell<\/em>, suggests that therapeutics targeting these stem cells may lead to new treatment options for patients, including a class of drugs currently used to manage high blood pressure.<\/p>\n \u201cWhile 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,\u201d said co-corresponding author Dr. Matthew Greenblatt<\/a>, 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.<\/p>\n Once the researchers had identified the elusive stem cells, they explored whether the findings could address an unmet clinical need for alternatives to surgery to treat lumbar spinal stenosis.<\/p>\n \u201cIdentifying 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\u2019s condition worsens and requires surgery to relieve the nerve compression,\u201d said study co-corresponding author Dr. Sravisht Iyer<\/a>, an associate professor of orthopedics at Weill Cornell and a spine surgeon at Hospital for Special Surgery (HSS). \u201cThe findings are exciting for their potential to change the way we deliver spinal care.\u201d<\/p>\n Search for a Master Tendon and Ligament Stem Cell <\/strong><\/p>\n Dr. Greenblatt was well equipped to lead the search. In 2018, he and his colleagues located the stem cell that initiates fracture repair in the outer layer of bone<\/a>. They went on to identify the stem cells that form the skull<\/a> and spine<\/a>.<\/p>\n Unlike bone, however, tendons and ligaments are relatively uniform tissues with fibroblast-like cells that are difficult to distinguish from one another. As a result, finding a bona fide tendon and ligament stem-cell population was a challenge.<\/p>\n \u201cWe analyzed thousands of individual cells and sorted them into individual cell types. Then we identified which one had the properties we associate with \u2018stemness,\u2019\u201d said Dr. Greenblatt. In other words, the rare cell population able to continually replenish itself and produce the mature cells needed to build and maintain these tissues. Studying mice, the researchers located the stem cells in a specialized anatomical niche within tendon and ligament tissue that serves as a reservoir for growth and repair.<\/p>\n Characterizing the mouse stem cell helped the researchers locate a human equivalent in ligament samples that Dr. Iyer had removed from patients during surgery with informed consent. The team\u2014which included first author Dr. Lingling Hu<\/a>, a postdoctoral fellow in Dr. Greenblatt\u2019s and Dr. Iyer\u2019s labs\u2014confirmed that the human stem cells could both self-renew and produce ligament cells, demonstrating clinical relevance.<\/p>\n Furthermore, they determined that these stem cells are not relegated only to the spine. \u201cWe looked in the kneecap ligament; we looked at the Achilles tendon; and everywhere we looked, we found this cell,\u201d said Dr. Greenblatt. \u201cSo, we think this is the universal stem cell for tendons and ligaments throughout the body.\u201d<\/p>\n Potential Therapeutic Target for Spinal Stenosis<\/strong><\/p>\n To find out if these cells are the culprits behind lumbar spinal stenosis, the researchers compared stem cells harvested from individuals with lumbar spinal stenosis to those isolated from spinal ligaments removed from people with herniated discs and no signs of stenosis. The patients provided informed consent pre-operatively.<\/p>\n