Collaborative Research: RECODE: Organoid model of growth plate development

University Of Colorado At Denver, Aurora CO

Investigators

Abstract

The growth plate is a cartilage tissue located at the end of children’s long bones that is responsible for bone growth. It begins as a cluster of stem cells that become specialized and organize themselves into columns to form a functioning growth plate. This process is driven by both chemical cues and mechanical forces, although it is unclear how they work together to form the structure and function of the growth plate. This Reproducible Cells and Organoids via Directed-Differentiation Encoding (RECODE) project will develop a reproducible growth plate organoid that will allow one to study how stem cells form a mature growth plate, which can lead to novel approaches for bone and cartilage regeneration particularly in children. This project will train a diverse group of graduate, undergraduate, and high school students in mathematical modeling, biomaterial development, and stem cell and developmental biology and will provide opportunities to the broader community through outreach activities and events open to the public. The overarching goal for this RECODE project is to gain fundamental insight into the link between biophysical cues, cellular differentiation, and cellular organization that leads to the development of a functioning growth plate. This project combines experimental and computational approaches to gain insight into the local cues that govern directional cell division (Task 1), chondrogenic differentiation followed by columnar organization (Task 2), and hypertrophic differentiation, the characteristic phenotype of the growth plate (Task 3). This project will uncover how biophysical cues combined with spatially localized biochemical cues dovetail to drive the self-assembly of stem cells into a growth plate organ with the appropriate structure and function. By utilizing novel tools in biology, advanced biomaterials in 3D printing, and physics-based mathematical modeling, this project will create the first growth plate organoid to date. This organoid will provide a model system for deeper study of stem cell and chondrocyte differentiation, in normal and abnormal bone growth. Understanding the mechanisms that direct the differentiation of MSCs into a mature growth plate organoid will help guide the design of novel biomaterials for regenerative medicine approaches to treat growth plate injury, an area that currently lacks a viable and clinically accepted treatment. This RECODE award is co-funded by the Physiological and Structural Systems Cluster in the Division of Integrative Organismal Systems, the Mechanics and Engineering Materials Cluster in the Division of Civil, Mechanical, and Manufacturing Innovation, and the Engineering Biology and Health Cluster in the Division of Chemical, Bioengineering, Environmental, and Transport Systems. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.