Scientists have inserted mRNA into mesenchymal stem cells (MSCs) to produce a drug delivery vehicle. Following systemic administration, the modified MSCs targeted and adhered to sites of inflammation, then released interleukin-10 that significantly reduced local swelling.
Historically, MSC-based treatments have had mixed results. MSCs exert their therapeutic effects in hit-and-run style. That is, MSCs are rapidly cleared after entering the bloodstream, typically within a few hours or days. Yet, despite the transience of MSC therapeutic action, a team of scientists reports that it has engineered MSCs that rapidly localized at a distant site of inflammation in an in vivo model, and delivered therapeutically relevant concentrations of the drug. The MSCs had been engineered enhanced homing and the expression of interleukin-10, which is not inherently produced by MSCs.
The team of scientists included members representing Brigham and Women's Hospital, the Harvard Stem Cell Institute, MIT, and Massachusetts General Hospital. The team, which published the results of its proof-of concept study in the October 3 issue of Blood, notes that its work is already drawing interest from biopharmaceutical companies.
“This opens the door to thinking of mRNA transfection of cell populations as next-generation therapeutics in the clinic, as they get around some of the delivery challenges that have been encountered with biological agents,” said Oren Levy, Ph.D., co-lead author of the study and instructor of medicine in the laboratory of research leader Jeffrey Karp, Ph.D. Dr. Karp, a Harvard Stem Cell Institute principal faculty member and associate professor at the Brigham and Women's Hospital, is also affiliated with Harvard Medical School and MIT.
“If you think of a cell as a drug factory, what we’re doing is targeting cell-based, drug factories to damaged or diseased tissues, where the cells can produce drugs at high enough levels to have a therapeutic effect,” said Dr. Karp.
The key to success was the use of triple-transfected MSCs. In addition to expressing interleukin-1-, the cells expressed, in the team’s words, “functional rolling machinery.” This machinery consisted of P-selectin glycoprotein ligand-1(PSGL-1) and Sialyl-Lewisx (SLeX). Basically, the cells expressed both the immunomodulating agent and adhesive surface proteins.