Building microenvironment-containing organoids from patient samples with single-cell precision


Year of Award:
2019
Status:
Active
Award Type:
R21
Project Number:
CA236685
RFA Number:
RFA-CA-18-002
Technology Track:
Molecular & Cellular Analysis Technologies
PI/Project Leader:
MANALIS, SCOTT R
Other PI or Project Leader:
Not Applicable
Institution:
MASSACHUSETTS INSTITUTE OF TECHNOLOGY
SummaryOrganoid models have recently emerged as an alternative, more realistic in vitro representation ofpatient tumors when compared to traditional 2D culture approaches. At a functional level, organoidshave proven useful as realistic tumor model to be used for ex vivo drug testing. Although organoidmodels can often accurately recapitulate the spatial organization of the tumor, they are typicallyderived from a single cell type (e.g., tumor cells or pluripotent stem cells) and existing tools formaking organoids with well-defined compositions are limited. To address this, we propose to developan instrument for building organoid co-cultures consisting of the major tumor, stromal, and immunecell types previously shown to play a role in drug resistance in multiple myeloma, by fluorescentlylabeling cells and dispensing them from patient samples into culture wells in a single step. Bymonitoring the growth and viability of these organoids and subjecting them to drug testing, we willdetermine the minimal functional unit that is sufficient to recapitulate the major tumor-stromainteractions of the multiple myeloma bone marrow niche. If successful, we envision that more realisticpatient-derived organoid models could lead to improved functional assays to test the susceptibility ofpatient samples to cancer therapeutics, with the potential goal of using these assays to guidetreatment decisions.