2008 Woodie Awards
Shape of tissues influences stem cell growth
Issue date: 9/25/08
In the field of developmental biology, and now recently in stem cell biology, it has long been thought that small molecules called morphogens control the fate of cells. These morphogens decide when an embryonic stem cell becomes a muscle cell or brain cell or any other type of cell.
New research shows these molecules have other roles as well. Sami Alom Ruiz, then at Hopkins and now at the University of Pennsylvania, and Chris Chen of U. Penn., have shown that morphogens play a role not only in determining cell fate, but also in the response to mechanical stresses such as stretching.
The goal of the work was simple: "To understand how tissue form can lead to differentiation of cells in the appropriate locations," Ruiz said.
"Understanding how differentiation is tied to tissue form will provide a better appreciation of how cells orchestrate morphogenetic processes as well as a roadmap for directing stem cell fates in regenerative therapies."
Using mesenchymal stem cells (MSCs) to study the effects of mechanical forces on stem cell fate, the researchers look at several different geometries to test growth of cells. MSCs are a multipotent stem cell, capable of forming cells involved in the formation of fat, cartilage and bone.
The researchers grew the MSCs in media that help to turn these cells into either adipocytes (fat cells) or osteoclasts (bone cells). They found that when they grew the MSCs on a flat surface so that the cells grew into what is known as a monolayer, or single layer of cells, the MSCs differentiated into both types of cells.
The interesting part is that the adipocytes preferentially grew in the center of the layer, whereas the osteocytes grew around the outside. This shows that cells can undergo cell determination based on the geometry of the structure in which they are growing.
They then asked what effect the structure had on the cell-fate determination. They grew cells on many different shapes, including a rectangle, square, annulus or ring, ellipse and sinusoidal bands. Each time they found that cells in the high stress regions - for instance, at the corner of a square - form osteocytes and those in the low stress regions form adipocytes.
New research shows these molecules have other roles as well. Sami Alom Ruiz, then at Hopkins and now at the University of Pennsylvania, and Chris Chen of U. Penn., have shown that morphogens play a role not only in determining cell fate, but also in the response to mechanical stresses such as stretching.
The goal of the work was simple: "To understand how tissue form can lead to differentiation of cells in the appropriate locations," Ruiz said.
"Understanding how differentiation is tied to tissue form will provide a better appreciation of how cells orchestrate morphogenetic processes as well as a roadmap for directing stem cell fates in regenerative therapies."
Using mesenchymal stem cells (MSCs) to study the effects of mechanical forces on stem cell fate, the researchers look at several different geometries to test growth of cells. MSCs are a multipotent stem cell, capable of forming cells involved in the formation of fat, cartilage and bone.
The researchers grew the MSCs in media that help to turn these cells into either adipocytes (fat cells) or osteoclasts (bone cells). They found that when they grew the MSCs on a flat surface so that the cells grew into what is known as a monolayer, or single layer of cells, the MSCs differentiated into both types of cells.
The interesting part is that the adipocytes preferentially grew in the center of the layer, whereas the osteocytes grew around the outside. This shows that cells can undergo cell determination based on the geometry of the structure in which they are growing.
They then asked what effect the structure had on the cell-fate determination. They grew cells on many different shapes, including a rectangle, square, annulus or ring, ellipse and sinusoidal bands. Each time they found that cells in the high stress regions - for instance, at the corner of a square - form osteocytes and those in the low stress regions form adipocytes.
Be the first to comment on this story