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BWH researchers ‘unlock’ key to targeting stem cells to specific tissues
11-08-2011
by Amy Swinderman  |  Email the author
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BOSTON—Although stem cell research has come a long way in the last two decades, significant hurdles to realizing their therapeutic potential remain. One of the biggest barriers to effective cell therapy is the inability of scientists to target cells to tissues of interest—but a team of researchers at Brigham and Women's Hospital (BWH) has devised an approach to address this challenge.  
 
Likening this approach to a "lock and key," the BWH have chemically incorporated homing receptors onto the surface of cells. Using a platform approach that preserves the mesenchymal stem cell (MSC) phenotype and does not require genetic manipulation, they modified the surface of MSCs with a nanometer-scale polymer construct containing sialyl Lewisx (SLeX) that is found on the surface of leukocytes and mediates cell rolling within inflamed tissue. The SLeX engineered MSCs exhibited a robust rolling response on inflamed endothelium in vivo and homed to inflamed tissue with higher efficiency, compared to native MSCs.  
 
"Essentially, the blood vessels in specific tissues all have certain 'locks' and 'keys,'" explains Dr. Jeffrey M. Karp, co-director of the Regenerative Therapeutics Center at BWH. "By knowing these 'locks,' we could attach the 'keys' to the surface of cells. As they circulate through the bloodstream, they only engage to the corresponding cells."  
 
Karp, who is also a principal faculty member of the Harvard Stem Cell Institute, was one of the authors of a study describing this approach, "Engineered Cell Honing," which was published in the Oct. 27 online edition of the American Society of Hematology journal Blood. Karp's colleagues on the study included researchers from the Massachusetts General Hospital, the Massachusetts Institute of Technology (MIT), Harvard Medical School, the Harvard Stem Cell Institute and Tufts University.  
 
The team is full of analogies to describe their approach: "By knowing the 'zip code' of the blood vessels in specific tissues, we can program the 'address' onto the surface of the cells to potentially target them with high efficiencies," Karp adds.  
 
The finding will go a long way in addressing many of the challenges associated with targeting stem cells to specific tissues—what Karp calls "the big unmet need of stem cell research. " While conventional cell therapies that include local administration of cells can be useful, they are typically more invasive, with limited potential for multiple doses. For example, "when treating heart attacks or heart failure, injecting the cells directly into the heart can be an invasive procedure, and typically this approach can only be performed once," Karp says.
 
Systemic infusion is desired, says Karp, as it minimizes the invasiveness of cell therapy and maximizes practical aspects of repeated doses.  
 
"We're getting to a point in time where one can obtain almost unlimited quantities of almost any cell type in the lab—but what I think is really the biggest limitation to moving cell therapies to the clinic is being able to deliver cells to targeted tissues in the body, while maintaining high survival and efficacy rates. We posed the question: Can we target cells to specific tissues using a non-viral approach that is chemical in nature? To do this, we covalently modified the cell surface using a very simple approach at ambient conditions. We chemically attached to the cell surface a ligand that can interact with something expressed in inflammation."  
 
The researchers concluded that, as the understanding of the mechanisms of cell trafficking grows, the ability to improve homing to specific tissues through engineered approaches should significantly enhance cell therapy by reducing the invasiveness of local administration, permitting repeat dosing and potentially reducing the number of cells required to achieve a therapeutic effect, ultimately providing better outcomes for patients.  
 
According to Karp, this approach can be used to systemically target bone-producing cells to the bone marrow to treat osteoporosis, cardiomyocytes to the heart to treat ischemic tissue, neural stem cells to the brain to treat Parkinson's disease or endothelial progenitor cells to sites of peripheral vascular disease to promote formation of new blood vessels.  
 
The approach will translate to the core technology of a new stem cell company, he adds.
 
"Most of the companies in this area have been focused on obtaining the right cell type and then delivering that cell, but the problem is that there hasn't been much innovation in the delivery area of this science that is critical," Karp says. "We are in the process of translating this technology and other cell modification approaches within a new startup company."
 
 
Code: E11091103

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