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 A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>