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Now it appears that even stem cells can come with GPS, thanks to a groundbreaking study led by Robert Sackstein, MD, PhD, and his colleagues in the Department of Dermatology at the Biomedical Research Institute of BWH.
By harmlessly modifying the surface of human mesenchymal stem cells—a type of adult stem cell that is the precursor of bone-forming cells called osteoblasts—researchers were able to direct the cells through the bloodstream into bone, where they matured into new bone cells.
“We are cautiously optimistic that our approach has utility for every application of stem-cell based therapeutics and, in particular, for treating osteoporosis,” said Sackstein.
Osteoporosis is the leading cause of disability in the world among older adults. “Half of all women and a quarter of men older than 50 will have bone fractures due to osteoporosis, with about 1.5 million fractures per year attributable to this disease in the U.S. alone, so the next step for our research is to move towards clinical trials to use this strategy to treat and hopefully cure this and other generalized bone diseases,” Sackstein said.
Before modifying the surface of the stem cell, the researchers studied white blood cells. “White blood cells in the bloodstream get to where they are needed faster and more accurately than any other type of cell because they express ‘homing receptors’ on their surface,” Sackstein said. “We found that human mesenchymal stem cells lack these homing receptors, but our studies also showed that they had a precursor form of a potent homing receptor called HCELL, which lacked only a particular sugar molecule to complete its structure.”
The researchers then developed the tools and method to add this key sugar molecule in just the right place to create HCELL without hurting the cells. When injected intravenously into mice, the HCELL-bearing human mesenchymal stem cells homed to bone and created patches of human bone within the mouse bone.
Beyond its usefulness to treat generalized bone diseases, the researchers concluded that this gateway technology could enable adult stem cell delivery to any site of tissue injury.
The stem cells were recruited to bone because HCELL docks on E-selectin, an adhesion molecule normally present on the lining of specialized blood vessels in bone. But E-selectin is also expressed prominently on blood vessels within any tissue in the body that is injured or is undergoing an inflammatory process. “In this way, HCELL would provide a routing cue to send the circulating stem cells to where they are needed, just like you need a zip code to deliver mail,” Sackstein said.
Sackstein and his colleagues received funding from the National Institutes of Health for this study. These study findings will appear in the February issue of Nature Medicine.