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] dishwe 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."
There are ways to get around this problem, but they have limitations. For example, cells can be put on a scaffold or biomaterial that releases drugs or other agents that affect their behavior. The cells, however, have to stay in close proximity to the material to be impacted by the agents. Cells can also be genetically modified with viruses to produce agents that will influence their behavior, but this has potential safety concerns.
The Karp team was inspired by the natural ability of many proteins and other agents to be transported in and out of cells. They already knew that cells could internalize the tiny synthetic particles used in the controlled delivery of drugscould these particles be used in cell therapy?
To find out, the researchers developed biodegradable particles about ten times smaller than a mesenchymal stem cell (MSC). They loaded these particles with a dye, placed them near living MSCs, and found that the cells did indeed internalize them without immediately spitting them out. "Initially, this was a major challenge," com
|Contact: Holly Brown-Ayers|
Brigham and Women's Hospital