Researchers at 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.
Boston, MA - In work that could jumpstart the promising field of cell therapy, in which cells are transplanted into the body to treat a variety of diseases and tissue defects, 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.
In the work, reported in the journal Biomaterials on January 26, the team reports creating tiny internal depots within human mesenchymal adult stem cells, which among other functions are key to the generation of several tissues. 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.
"This work could allow programmable cell therapies where the cell or the agent is the therapeutic," says Jeffrey Karp, leader of the work and co-director of the Center for Regenerative Therapeutics (ReGen Rx) at BWH. "For example, 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."
Next, they replaced the dye with an agent known to spur MSCs to differentiate into osteoblasts, the cells that make bone. They found that not only did MSCs containing the depots differentiate into osteoblasts, but so did MSCs without depots that were nearby and even much further away. "We demonstrated that the fate of particle-carrying cells could be controlled, as well as the fates of neighboring and distant cells," says Debanjan Sarkar, co-first author of the paper and now a professor at the University of Buffalo.
Additional authors are Grace S. L. Teo of HST and Christopher V. Carman of Beth Israel Deaconess Hospital.
To date the team has demonstrated the engineered cells in laboratory systems designed to mimic the body. 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," says Karp, whose team has filed for a patent on the work.
This work was funded by the National Institutes of Health, the American Heart Association, and the National Science Foundation.
Contact: Holly Brown-Ayers firstname.lastname@example.org 617-534-1603 Brigham and Women's Hospital