Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecule supporting hematopoietic recovery after transplantation of blood stem cells identified

28.01.2019

Transplantation of blood stem cells (haematopoietic stem cell transplantation) is an important treatment option for patients with haematopoietic disorders. This method is also applied in hematopoietic stem cell-directed gene therapy. Researchers from the Paul-Ehrlich-Institut (PEI), Federal Institute for Vaccines and Biomedicines identified the endothelial protein-C receptor (EPCR) on hematopoietic stem cells to improve stem cell transplantation. These research results are reported in the journal Blood in its online version of 25.01.2019.

Blood cells are constantly renewed – platelets for instance have a life time of a few days and red blood cells between one and three months. These blood cells derive from blood stem cells (haematopoietic stem cells) residing in the bone marrow and differentiating into all different blood cell types.


Bone marrow cells of the mouse (cytospin, May-Grünwald / Giemsa staining)

Source: PEI

They can self-renew and switch to quiescence to protect themselves against exhaustion caused by frequent cell division. When the process of differentiation, self-renewal, and quiescence is disturbed, blood cell disorders can develop.

This can be the case, for instance, in blood cell diseases such as leukemia or aplastic anaemia, which, in the event of loss of blood stem cells, lead to a blood cell deficiency. A possible therapy option by aplastic anaemia is the transplantation of blood stem cells from suitable donors (haematopoietic stem cell transplantation).

Which factors will affect the success of this treatment? This question was asked by Professor Ute Modlich, head of the research group "Gene Modification in Stem Cells" at the PEI and her co-workers. For this purpose, she used a mouse model of aplastic anaemia.

In the mice, the central signal pathway of the cytokine thrombopoietin (Thpo) is blocked by deleting its receptor Mpl (myeloproliferative leukaemia virus oncogene, Mpl-deficient mice).

These mice mimic the phenotype of patients with aplastic anaemia caused by inactivating mutations in the same pathway. Blood stem cells of Mpl-deficient mice engraft and expand only very poorly after transplantation.

The Mpl receptor activates various pathways. Which pathway is important for the stem cell preserving function of Thpo/Mpl? To find the answer, researchers expressed potential Thpo-target genes with lentiviral vectors in Mpl-deficient blood stem cells. These cells were transplanted into Mpl-deficient recipient mice and hematopoietic recovery evaluated.

Of the five candidate genes studied, the surface protein EPCR (endothelial protein-C receptor) proved to be an important player: Was this surface protein present on blood stem cells, they expanded and could also transition into quiescence.

In mice which received these modified stem cells (Epcr+Mpl-deficient), a large number of donor cells could be detected in the bone marrow appropriately fast. In further experiments, the PEI researchers proved that Epcr marked the engrafting blood stem cells also in normal haematopoiesis and that they expanded well after stem cell transplantation.

Epcr is known as co-receptor for the protease-activated receptor (PAR1) on endothelial cells. This receptor can be activated by its ligand, activated protein C (aPC). Professor Modlich explained the significance of these research results by stating “We have identified a target structure which we may be able to use to support blood stem cell transplantations. This could be useful in particular in gene therapy where blood stem cells are genetically modified in culture before these cells are transplanted.”


The Paul-Ehrlich-Institut, the Federal Institute for Vaccines and Biomedicines, in Langen near Frankfurt/Main is a senior federal authority reporting to the Federal Ministry of Health (Bundesministerium für Gesundheit, BMG). It is responsible for the research, assessment, and marketing authorisation of biomedicines for human use and immunological veterinary medicinal products. Its remit also includes the authorisation of clinical trials and pharmacovigilance, i.e. recording and evaluation of potential adverse effects.

Other duties of the institute include official batch control, scientific advice and inspections. In-house experimental research in the field of biomedicines and life science form an indispensable basis for the manifold tasks performed at the institute.

The Paul-Ehrlich-Institut, with its roughly 800 members of staff, also has advisory functions nationally (federal government, federal states (Länder)), and internationally (World Health Organisation, European Medicines Agency, European Commission, Council of Europe etc.).

Originalpublikation:

Kohlscheen S, Schenk F, Rommel M, Cullmann K, Modlich U (2019): Endothelial protein C receptor supports hematopoietic stem cell engraftment and expansion in Mpl-deficient mice.
Blood 133 Jan [Epub ahead of print].

doi: https://doi.org/10.1182/blood-2018-03-837344

Weitere Informationen:

http://www.bloodjournal.org/content/early/2019/01/25/blood-2018-03-837344?sso-ch... - Abstract
https://www.pei.de/EN/information/journalists-press/press-releases/2019/01-surfa... - this press release on the PEI Website

Dr. Susanne Stöcker | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Cell division in plants: How cell walls are assembled
20.02.2019 | Martin-Luther-Universität Halle-Wittenberg

nachricht Antibiotic resistances spread faster than so far thought
18.02.2019 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Light from a roll – hybrid OLED creates innovative and functional luminous surfaces

Up to now, OLEDs have been used exclusively as a novel lighting technology for use in luminaires and lamps. However, flexible organic technology can offer much more: as an active lighting surface, it can be combined with a wide variety of materials, not just to modify but to revolutionize the functionality and design of countless existing products. To exemplify this, the Fraunhofer FEP together with the company EMDE development of light GmbH will be presenting hybrid flexible OLEDs integrated into textile designs within the EU-funded project PI-SCALE for the first time at LOPEC (March 19-21, 2019 in Munich, Germany) as examples of some of the many possible applications.

The Fraunhofer FEP, a provider of research and development services in the field of organic electronics, has long been involved in the development of...

Im Focus: Regensburg physicists watch electron transfer in a single molecule

For the first time, an international team of scientists based in Regensburg, Germany, has recorded the orbitals of single molecules in different charge states in a novel type of microscopy. The research findings are published under the title “Mapping orbital changes upon electron transfer with tunneling microscopy on insulators” in the prestigious journal “Nature”.

The building blocks of matter surrounding us are atoms and molecules. The properties of that matter, however, are often not set by these building blocks...

Im Focus: University of Konstanz gains new insights into the recent development of the human immune system

Scientists at the University of Konstanz identify fierce competition between the human immune system and bacterial pathogens

Cell biologists from the University of Konstanz shed light on a recent evolutionary process in the human immune system and publish their findings in the...

Im Focus: Transformation through Light

Laser physicists have taken snapshots of carbon molecules C₆₀ showing how they transform in intense infrared light

When carbon molecules C₆₀ are exposed to an intense infrared light, they change their ball-like structure to a more elongated version. This has now been...

Im Focus: Famous “sandpile model” shown to move like a traveling sand dune

Researchers at IST Austria find new property of important physical model. Results published in PNAS

The so-called Abelian sandpile model has been studied by scientists for more than 30 years to better understand a physical phenomenon called self-organized...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Global Legal Hackathon at HAW Hamburg

11.02.2019 | Event News

The world of quantum chemistry meets in Heidelberg

30.01.2019 | Event News

Our digital society in 2040

16.01.2019 | Event News

 
Latest News

Terahertz wireless makes big strides in paving the way to technological singularity

19.02.2019 | Information Technology

Researchers find trigger that turns strep infections into flesh-eating disease

19.02.2019 | Health and Medicine

Light from a roll – hybrid OLED creates innovative and functional luminous surfaces

19.02.2019 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>