Brown University

Toni-Marie Achilli

Jeffrey R Morgan

Anubhav Tripathi

Stephanie McCalla

Jacquelyn Youssef Schell

Drugs are screened for affects on inhibiting efflux pumps and blocking gap junction communication in tumors by culturing cells to thereby form self-assembled spheroids and incubating the spheroids. Uptake of a substrate of the efflux pump and distribution of a substrate for the efflux pump within the spheroids is imaged to thereby select drugs that inhibit the efflux pump or do not block gap junction communication. Selected drugs can then be employed to treat a tumor.

Differential effects of drugs on transport in a multi-layer 3D spheroid model

The candidates are screened and then employed by administering to patients in need thereof of a drug candidate that affects heterotypic intercellular mechanotransduction. At least two types of cells are labeled with distinct intracellular fluorescent marker labels and combined to form a cell suspension and cultured to form a microtissue, such as spheroids. The cells or the spheroids are combined with a drug candidate, either before, during or after forming the spheroids. The distribution of the different cell types is compared to that of essentially the same suspension culture in the absence of the drug candidate. Alternatively, the cell power of cells cultured in a non-adherent mold that determines at least in part, the shape of microtissue formed is measured and compared with essentially the same cell suspension cultured in the same manner in the absence of a drug candidate. A patient in need thereof can be administered a drug identified as affecting heterotypic intercellular mechanotransduction. Alternatively, a macrotissue can be formed that is employed in therapeutic treatment of a patient in need thereof.

Growing community of inventors

Providence, RI, United States of America

Toni-Marie Achilli