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February 07, 2011

Engineered cells could usher in programmable cell therapies

Researchers at Brigham and Women’s Hospital (BWH) have engineered cells that could solve one of the key challenges associated with the procedure: control of the cells and their microenvironment following transplantation. Researchers at Brigham and Women's Hospital have engineered human mesenchymal adult stem cells to contain tiny depots that can influence the behavior of the cells and those surrounding them, including their survival, differentiation, or production of a therapeutic proteins. These depots can slowly release a variety of agents to influence the behavior of not only the cells containing the depots, but also those close to them and even much farther away. The team demonstrated this by prompting mesenchymal stem cells to differentiate into the cells that make bone.

“Ten to fifteen years from now, people will visit cell infusion centers to receive routine therapy for multiple diseases and tissue defects,” predicts Karp, who also holds appointments through Harvard Medical School, Harvard Stem Cell Institute, and the Harvard-MIT Division of Health Sciences and Technology (HST). For example, a person who has had a heart attack could be infused with cells that could help stimulate regeneration of new heart cells to replace those that have died and prevent eventual heart failure.

They are in the process of translating the work to animals. “If it works in vivo, it could have a significant impact globally on cell therapy."



Today, however, there is only one cell therapy that has saved tens of thousands of lives: bone marrow transplantation. In this procedure healthy blood stem cells home in to the bone marrow to regenerate the blood system of cancer patients following bone marrow ablation through chemotherapy or radiation.

One of the reasons for the lack of success of other cell therapies is the inability to control the cells and the host’s response following transplantation, says Karp. “We can exhibit exquisite control over cells in a [laboratory] dish—we can get them to do whatever we want. But when we transplant them into the body, their fate and function are at the mercy of the biological milieu. We typically lose complete control and this prevents us from achieving the promise of cell therapy.”

The new work could allow depots containing specific agents could enhance cell survival or expression of a particular growth factor. Cells could also be used as a delivery vehicle to shuttle drugs to target tissues that may be useful to accelerate tissue regeneration, or to deliver chemotherapeutics to tumors while minimizing systemic side effects
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