Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Opening up the stem cell niche: German science team modifies the way for research of blood stem cells

09.03.2009
Newly developed mouse model allows for transplantation of blood stem cells without previous irradiation of the recipients

Understanding the function of hematopoietic stem cells (HSCs) that provide life-long all components of our immune system requires research under physiological conditions in a living organism (in vivo).

To study their proper control and potency, HSCs are transplanted into appropriate recipients. However, there have been two major obstacles preventing engraftment of donor HSCs into recipients: 1. In cases of genetically unrelated donors and recipients, the donor cells are rejected by the recipient's immune system. 2.

HSCs rarely enter the stem cell 'niche', which is a specialized space structure in the bone marrow. To open access for HSCs to these stem cell niches, and to suppress rejection of donor HSCs, recipients are usually irradiated. A team from the University of Ulm around Claudia Waskow (now at the Center for Regenerative Therapies Dresden - CRTD) and Hans-Reimer Rodewald, together with Rosel Blasig from the Leibniz-Institute for Molecular Pharmacology in Berlin, developed a new mouse model, which allows the transplantation of HSCs without the need for previous irradiation, facilitating the analysis of stem cell function.

In the current issue of Nature Methods, the scientists reveal the trick: "We combined three genetic mutations and could show that only this combined triple mutant allows for successful HSC transplantation without irradiation", explains Dr. Claudia Waskow of the CRTD. 'All three mutations were known, but we went one step further and brought them all together in one single mouse strain.' Normally, donors and recipients are histoincompatible, i.e. their immune systems reject each others tissues. This is also true for donor HSCs that are attacked by the recipient's immune system and consequently rejected. Irradiation reduces the risk of graft rejection, because it destroys cells of the recipient's immune system. However, irradiation is harmful for the body and has strong side effects on many cell types, for example gut cells. The second hurdle in HSC transplantation is to make donor HSCs efficiently enter and continuously stay in the specialized niches that support the survival and function of all HSCs. In a healthy recipient, these niches are occupied by endogenous blood stem cells. While they are damaged and depleted by irradiation, they can be replaced by donor HSCs. With the newly developed mouse model, irradiation is no longer required: The mutation in the growth factor receptor Kit (KitW/Wv) 'weakens' the recipient's stem cell compartment and therefore makes space for incoming donor stem cells. The other two mutations that were introduced into these 'universal recipients' are known to prevent rejection of donor HSCs by the recipient's immune system. Thus, these mice appear to accept all blood stem cells regardless of the mouse strain origin of the HSCs.

What exactly is now the advance in using a non-irradiated living organism? 'It is only possible to study the regeneration of HSCs in vivo. Observations in tissue culture are often not applicable to in vivo situations', states Waskow. 'Because we do not need to irradiate the mice anymore, all organs including the bone marrow remain undamaged, which helps us to study the normal physiological behavior of transplanted HSCs and the normal HSC niches much better'. Important processes of blood stem cells such as the 'homing' of HSCs can now be studied under more natural conditions. 'Homing' of HSCs to their appropriate locations in the body occurs when transplanted cells move from the blood into the bone marrow after transplantation.

It remains to be seen whether the new mouse line will accept human HSCs in a better or more sustained manner than in currently available mouse models. If so, the results of this study could lead to a better understanding of the regulation of human blood formation. Even studies on human infectious diseases or cancer may become feasible. In future studies, Claudia Waskow and Hans-Reimer Rodewald want to concentrate on these possibilities and thereby contribute to a better understanding of the generation and maintenance of the immune system by HSCs

Claudia Waskow, Vikas Madan, Susanne Bartels, Céline Costa, Rosel Blasig, Hans-Reimer Rodewald "Hematopoietic stem cell transplantation without irridation" Nature Methods. Online publication ahead: march 8, 2009 | doi: 10.1038/nmeth.1309.

The abstract of the article can be viewed under specification of the doi-Number from March 8., 6pm here: http://dx.doi.org/. For the full article please contact press@nature.com or the press office of the CRTD.

Background: DFG-Center for Regenerative Therapies Dresden (CRTD)
Started in January 2006 as the DFG Center for Regenerative Therapies Dresden, the CRTD became the Cluster of Excellence "From cells to tissues to therapies: Engineering the cellular basis of regeneration" of the Dresden University of Technology in October 2006. The goal of the center is to develop novel regenerative therapies for diseases like diabetes, Parkinson, or Cardiovascular diseases. The CRTD is set up as an interdisciplinary network of over 80 principal investigators from seven research institutes in Dresden and several economic partners.
Contact for Journalists:
Katrin Bergmann, Press officer at the CRTD
Phone: +49 351 463 40347, E-Mail: katrin.bergmann@crt-dresden.de
Claudia Waskow, Research group leader at the CRTD
Phone: +49 351 458 6448, E-Mail: claudia.waskow@crt-dresden.de
Hans-Reimer Rodewald, Institute for Immunology, University Hospital Ulm,
Phone: +49 731 5006 5200, E-Mail: hans-reimer.rodewald@uni-ulm.de

Katrin Bergmann | idw
Further information:
http://www.crt-dresden.de
http://www.uni-ulm.de/klinik/immunologie/

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 >>>