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 Could this protein protect people against coronary artery disease?
17.11.2017 | University of North Carolina Health Care

nachricht Microbial resident enables beetles to feed on a leafy diet
17.11.2017 | Max-Planck-Institut für chemische Ökologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>