Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Crowding stem cells’ personal space directs their future

19.04.2004


Johns Hopkins scientists report that restricting the shape and personal space of human stem cells from bone marrow is more important than any known molecular signal in determining the cell type they become.



Understanding the signals that tell stem cells what type of cell to become, and then harnessing those cues to get a single desired cell type, is key to any effort to use these or more primitive embryonic stem cells to regenerate or repair damaged tissue.

In the April issue of Developmental Cell, the Hopkins researchers report that mesenchymal (pronounced mez-EHN-kih-mal) stem cells forced to be spherical efficiently transform into precursors to fat cells, while those allowed to stretch and flatten move closer to becoming bone cells. These stem cells can naturally become fat cells, cartilage, bone cells, or smooth, cardiac or skeletal muscle.


"The types of cells that come from mesenchymal stem cells all have shapes specific to their functions, so we wondered whether the stem cells’ shapes could actually direct their differentiation," says Christopher Chen, M.D., Ph.D., an assistant professor of biomedical engineering at Johns Hopkins. "The answer is that shape is critical to the stem cells’ differentiation. It can actually induce molecular signals known to encourage fat cell or bone cell development and causes complete, uniform differentiation."

In the first week of laboratory studies, about 45 percent of stem cells forced to be round moved toward fat cell development, and 50 percent of spread-out cells got closer to being bone cells. By four weeks, all cells had followed the path dictated by their shape, Chen says, making shape the most powerful factor in whether human mesenchymal stem cells become fat or bone in the lab.

Ever since these stem cells were first isolated in the late 1990s, scientists have recognized that which cell type they become depends on the density at which they are grown in the lab. But while sparse growth was recommended to get bone cells, and congested growth was recommended to increase the amount of fat cells, no one knew why.

To really understand whether it was the cells’ shape or some aspect of their neighbors that directed differentiation, M.D./Ph.D. candidate Rowena McBeath used a special technique, developed in Chen’s lab, that restricts individual cells to small spaces without requiring cellular neighbors to do the crowding.

The technique, called micropatterning, uses technology that was initially developed for the semiconductor industry. Using a rubber-like material, stamps are created that each have a specific pattern of microscopic squares, each coated with a protein that attracts cells (fibronectin). The stamp is then used to transfer the pattern to a surface, resulting in "islands" to which cells stick. The researchers can precisely control the size of the islands, and consequently whether cells will form a ball or stretch out.

"With this tool we can restrict the ability of individual cells to spread, and we can do so thousands of cells at a time," says Chen.

McBeath’s experiments showed that mesenchymal stem cells on the small islands balled up and, biologically speaking, moved closer to becoming fat cells, while those on large islands stretched out and got closer to becoming bone cells. In subsequent experiments, she proved that shape can’t be overcome by known molecular signals traditionally used to encourage mesenchymal stem cells to differentiate into either fat or bone cell precursors.

"Stretching out pushes the stem cells toward becoming bone cell precursors, and no collection of fat-encouraging signals was able to subsequently overcome the early effect of shape," says McBeath, an M.D./Ph.D. candidate in the Cellular and Molecular Medicine graduate program.

McBeath also showed that a molecule called RhoA, known to be activated when cells spread out, can mimic the effect of shape on the stem cells’ differentiation. Perpetually active RhoA caused the stem cells to move toward bone, while inactive RhoA pushed them toward becoming fat cells, even when exposed to factors known to encourage differentiation toward the opposite cell type.

"Remarkably, when the cells were simply grown in regular dishes in the lab, RhoA’s activation or inactivation overrode signals usually used to direct their growth toward fat or bone," says McBeath. "But altering RhoA activity couldn’t force a round cell to become a bone precursor, or a spread cell to become a fat cell on our micropatterns."

However, she discovered that activating the enzyme RhoA kinase or ROCK, which is turned on by RhoA, caused even balled cells to differentiate toward bone. On April 8, in recognition of her work, McBeath received the Nupur Dinesh Thekdi Research Award as part of Hopkins’ 27th annual Young Investigators’ Day.

Next, the researchers will work on figuring out exactly how shape dictates the stem cells’ futures and what role ROCK and RhoA play in the process.

Authors on the report are McBeath, Chen, Dana Pirone, Celeste Nelson and Kiran Bhadriraju, all of Johns Hopkins. The research was funded by the National Institute of General Medical Sciences, the National Institutes of Health’s Medical Scientist Training Program, the Ruth L. Kirschstein National Research Service Award, and The Whitaker Foundation.

Joanna Downer | EurekAlert!
Further information:
http://www.developmentalcell.com
http://www.hopkinsmedicine.org/press/2003/JANUARY/030127.HTM

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>