Small molecule helps get stem cells to sites of disease and damage

An industry-academic research collaboration yields a new strategy for delivering stem cells to the right location

IMAGE:Researchers identified a small molecule that can be used to program mesenchymal stem cells (blue and green) to home in on sites of damage. view more

Credit: Oren Levy, Brigham and Women's Hospital

Bioengineers from Brigham and Women's Hospital (BWH) with collaborators at the pharmaceutical company Sanofi have identified small molecules that can be used to program stem cells to home in on sites of damage, disease and inflammation. The techniques used to find and test these small molecules may represent important tools in advancing cell-based therapy, offering a new strategy for delivering cells to the right locations in the body. The results of their work appear online this week in Cell Reports.

Through a collaborative research project, the research team tested more than 9,000 compounds, and used a multi-step approach - including a sophisticated microfluidics set up and novel imaging technique - to narrow in on and test the most promising compounds.

"There are all kinds of techniques and tools that can be used to manipulate cells outside of the body and get them to do almost anything we want, but once we transplant cells we lose complete control over them," said co-senior author Jeff Karp, PhD, an associate professor at BWH, Harvard Medical School, and principal faculty at the Harvard Stem Cell Institute. "Through this collaboration, we've been able to identify small molecules that can be used to treat cells outside of the body, programming them to target blood vessels in diseased or damaged tissue."

Small molecules offered the team several advantages including the ability to use a safe and relatively simple procedure to pre-treat the cells before injecting them intravenously.

"There's a great need to develop strategies that improve the clinical impact of cell-based therapies," said co-first author Oren Levy, PhD, an instructor in medicine at BWH. "If you can create an engineering strategy that is safe, cost effective and simple to apply, that's exactly what we need to achieve the promise of cell-based therapy."

Karp's team at the Brigham had previously found that it is possible to use bioengineering techniques to chemically attach molecules to the surface of a cell that act as a GPS, guiding the cell to the site of inflammation. These findings indicated that targeted delivery of cells was possible, but a scalable approach would be needed to impact patients.

"At BWH, we had laid the groundwork. Our collaborators at Sanofi have complementary expertise in screening for small molecules, deep understanding of the biology and unmet needs, and an exceptional ability to bring new therapeutics to the clinic," said Karp. "Defined goals and both teams working seamlessly together created perfect synergy. We learned so much from each other."