Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers find that one type of stem cell creates a niche for another type in bone marrow

13.08.2010
Understanding how blood stem cells are maintained within the niche offers new opportunities to exploit them therapeutically

Cold Spring Harbor, N.Y. – Hematopoietic stem cells (HSCs) have two unique abilities that are prized by medical researchers: to self-renew and to develop into any kind of blood cell, which enables them to replenish the entire blood and immune system. Scientists have traced these qualities to a distinct locale or niche within the bone marrow that HSCs home in on, but the identity and function of the niche-forming constituents have not been clearly defined.

Now, the precise source of HSC maintenance and regulation within the bone marrow has been discovered by Cold Spring Harbor Laboratory (CSHL) researchers and members of a multi-institutional team. In a study to be published in Nature on August 12th, the collaborators report that the HSCs retain their unique features in response to signals from another stem cell population, the mesenchymal stem cells (MSCs), which create a supportive bone marrow niche for the HSCs.

"This is the first demonstration that one type of stem cell can regulate another type of stem cells," says CSHL scientist Grigori Enikolopov, Ph.D. "Having a detailed understanding of how HSCs are maintained within the niche microenvironment offers new opportunities to better exploit these cells for therapeutic use."

The path to this discovery originates from Enikolopov's efforts to develop reliable ways of distinguishing stem cells from other cell types. Previously, his group found that various types of stem cells express a protein called nestin. In recent years, they have detected and analyzed stem cell populations located in niches throughout the body using mice genetically engineered such that nestin-expressing cells also produce a fluorescent marker, making it possible to visually track these cells.

One location where the CSHL researchers found these nestin-expressing cells was the bone marrow, but these cells proved to not be HSCs. To find the identity and function of these mystery cells, they teamed up with a multi-institutional group led by Paul Frenette, M.D., of Mount Sinai School of Medicine, and which also included scientists from Harvard Medical School and the Albert Einstein College of Medicine.

Examining bone marrow sections from the nestin-expressing mice and based on the presence of various molecules on the populations of cells found within, the team identified the nestin-expressing cells as MSCs. These cells, which outnumber the HSCs 10:1, were either in direct contact with the HSCs or in clusters around them.

"This close proximity suggested that there might be some kind of molecular signaling or cross-talk going on that might control HSC maintenance," explains Enikolopov, who has been investigating the consequence of this kind of cell-cell dialogue during tissue and organ development. "One hypothesis is that this interaction directs and regulates growth by teaching different types of cells where they ought to locate themselves and what they should do there."

This seems to be the case, at least in the bone marrow, as the collaborators found that altering the numbers of MSCs has a corresponding effect on the numbers of HSCs. Increasing the numbers of MSCs by injecting mice with a growth hormone caused HSCs to double in number. Inhibiting MSC proliferation via infusions of growth-inhibiting proteins, on the other hand, was followed by a dip in HSC numbers.

The collaborators also explored the consequence of completely eradicating bone marrow MSCs using genetic tools developed in Enikolopov's lab. The CSHL scientists created mice in which only nestin-expressing cells—the MSCs—were programmed to carry a receptor for a toxin molecule. Injecting mice with the toxin thus selectively wiped out the MSCs. As a result, the scientists observed a four-fold reduction in the numbers of HSCs in the bone marrow of these mice. In the absence of bone marrow MSCs, large numbers of HSCs injected into the mice also failed to make their way to the bone marrow.

The collaborators found that genetic factors that are essential for HSC maintenance are highly concentrated within the neighboring MSCs. "The expression of these factors are least 500-fold higher in the MSCs than in other bone marrow cells, which shows why HSCs are so highly dependent on the MSCs," says Enikolopov.

"These results are a definitive indication that the MSCs are required for HSC maintenance as well as their homing to the bone marrow," says Tatyana Michurina, Ph.D., a research investigator in Enikolopov's laboratory who is an expert on both MSCs and HSCs. "After studying them as separate entities for years, it was such a surprise to discover that it was the MSCs that helped the HSCs to remain stem-like and primitive."

"These findings suggest that if we can control the niche, we can also manipulate the HSC population within," says Enikolopov. Pharmacological targeting of the niche might help enhance stem cell production for use in regeneration therapies or might help stave off adverse events like leukemia or other disorders where stem cells proliferate out of control.

The CSHL researchers were supported by a grant from the National Institute of Mental Health and a generous contribution by the Ira Hazan Fund.

"Mesenchymal and haematopoietic stem cells form a unique bone marrow niche" appears online on August 12th in Nature. The full citation is: Simon Mendez-Ferrer, Tatyana V. Michurina, Francesca Ferraro, Amin R. Mazloom, Ben D. MacArthur, Sergio A. Lira, David T. Scadden, Avi Ma'ayan, Grigori N. Enikolopov & Paul S. Frenette. The paper is available online at: http://www.nature.com/nature/journal/v466/n7308/full/nature09262.html

Cold Spring Harbor Laboratory (CSHL) is a private, not-for-profit research and education institution at the forefront of efforts in molecular biology and genetics to generate knowledge that will yield better diagnostics and treatments for cancer, neurological diseases and other major causes of human suffering.

Hema Bashyam | EurekAlert!
Further information:
http://www.cshl.edu

Further reports about: CSHL HSC MSC Nature Immunology bone marrow cell type cold fusion neurological disease stem cells

More articles from Life Sciences:

nachricht Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>