In a groundbreaking study, Robert Sackstein, MD, PhD, and colleagues in the Department of Dermatology at the Biomedical Research Institute at Brigham and Women’s Hospital (BWH) harmlessly modified the surface of human mesenchymal stem cells (a type of adult stem cell that is the precursor of bone forming cells called osteoblasts), which directed the cells through the bloodstream into bone, where they matured into new bone cells.
“Without genetically reprogramming a stem cell, which could cause adverse effects, we were able to navigate the cell to a predetermined location – a necessary first step towards achieving tissue regeneration,” said Sackstein, who is a bone marrow transplant physician at BWH. “Stem cells must have a routing cue to traffic to where they’re needed, just like you need a zip code to deliver mail.”
The Sackstein lab previously discovered the cell surface molecule HCELL, which is a homing receptor that seeks out the adhesion molecule E-selectin found on the lining of certain blood vessels. Specifically, HCELL docks on E-selectin, allowing the cell to exit the blood and enter a target tissue. All prior attempts to intravenously inject mesenchymal stem cells to treat generalized bone diseases were thwarted by the fact that the cells could not migrate to bone by simply being injected into the bloodstream.
In the current study, Sackstein and colleagues innocuously chemically engineered the surface of human mesenchymal stem cells to express HCELL. Next, these cells were injected intravenously into mice, where they migrated to bone and made islands of human bone within the mouse bone. This occurred because blood vessels in bone continually express E-selectin, thereby recruiting the HCELL-bearing stem cells to that site.
Beyond its usefulness to treat generalized bone diseases, the researchers concluded that this gateway technology should enable adult stem cell delivery to any site of tissue injury because E-selectin is typically expressed on blood vessels within damaged tissue, including tissue injured by stroke or heart attack.
“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 world-wide among older adults. Half of all woman and a quarter of men older than 50 will have bone fractures due to osteoporosis, 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.”
Illustration: Osteoblasts in developing bone. –Wikipedia.
Brigham and Women's Hospital Press Release (01/14/08)
US News & World Report (01/14/08)
Dental Plans (01/14/08)
Health Central (01/14/08)
Abstract (Nature Medicine 14, 181 – 187, 2008)