Hit-and-Run Action of Stem Cells Exploited for Targeted Drug Delivery

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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.
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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.
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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.) D; ^% ?- b9 T

* L8 L" X) Z& J* a) O“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.3 i% G; ~) |6 c. X* z5 G2 a

- P$ f# h9 t' N9 K4 @. j/ u“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.4 I+ Z4 h, {3 o" A5 z

+ I0 n  x) Y; {! o* }2 E9 ~% TThe 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.
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