Organoid models have recently emerged as an alternative, more realistic in vitro representation of patient tumors when compared to traditional 2D culture approaches. At a functional level, organoids have proven useful as realistic tumor model to be used for ex vivo drug testing. Although organoid models can often accurately recapitulate the spatial organization of the tumor, they are typically derived from a single cell type (e.g., tumor cells or pluripotent stem cells) and existing tools for making organoids with well-defined compositions are limited. To address this, we propose to develop an instrument for building organoid co-cultures consisting of the major tumor, stromal, and immune cell types previously shown to play a role in drug resistance in multiple myeloma, by fluorescently labeling cells and dispensing them from patient samples into culture wells in a single step. By monitoring the growth and viability of these organoids and subjecting them to drug testing, we will determine the minimal functional unit that is sufficient to recapitulate the major tumor-stroma interactions of the multiple myeloma bone marrow niche. If successful, we envision that more realistic patient-derived organoid models could lead to improved functional assays to test the susceptibility of patient samples to cancer therapeutics, with the potential goal of using these assays to guide treatment decisions.

Public Health Relevance

Organoids have proven useful as realistic tumor model to be used for ex vivo drug testing however they are often derived from a single cell type (e.g., tumor cells or pluripotent stem cells) and existing tools for making organoids with well-defined compositions are limited. To address this, we propose to develop an instrument for building organoid co-cultures consisting of the major tumor, stromal, and immune cell types previously shown to play a role in drug resistance in multiple myeloma, by fluorescently labeling cells and dispensing them from patient samples into culture wells in a single step. If successful, we envision that more realistic patient-derived organoid models could lead to improved functional assays to test the susceptibility of patient samples to cancer therapeutics, with the potential goal of using these assays to guide treatment decisions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA236685-02
Application #
9959372
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Sorg, Brian S
Project Start
2019-09-01
Project End
2022-08-31
Budget Start
2020-09-01
Budget End
2021-08-31
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Engineering (All Types)
Type
Biomed Engr/Col Engr/Engr Sta
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142