Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

16.07.2019

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red blood cells, platelets, and white blood cells (leucocytes).


Fig1: Illustration of the concept using 3D fluorescence images as bio. templates for cell migration simulations (red: vessels, green: megacaryocytes, blue: Hemapoietic stem cells, cyan: Neutrophils

Rudolf-Virchow-Zentrum, Uni Würzburg


Fig 2: Simulation of cell migration in bone marrow with adjustable parameters as indicated.

Rudolf-Virchow-Zentrum, Uni Würzburg

One of the most prominent white blood cell types are neutrophils – they help the body fight against infections and are the most abundant subpopulation of leukocytes. They are short-lived and highly mobile, and can enter parts of tissue where other cells/molecules cannot.

All hematopoietic cells that develop in the bone marrow must cross the blood vessel wall to enter the circulation system. Blood platelets are released by bigger vessel-penetrating protrusions of huge, largely immobile progenitor cells, named megakaryocytes.

In this way mature megakaryocytes produce platelets and release them into the blood circulation to maintain constant platelet counts. In addition, they actively regulate hematopoietic stem cell accumulation in a positive as well as negative manner.

Imaging the entire bone marrow with subcellular resolution to understand how all the players act in concert is still challenging. The research groups of Prof. Katrin Heinze and Dr. David Stegner established a profound 3D image reconstruction and segmentation pipeline for different bone marrow components.

These segmented objects, originally derived from Light Sheet Fluorescence Microscopy, then serve as templates (see Figure 1) for computational simulations of cell distributions and their migration behavior in the bone marrow.

Megakaryocytes influence cell migration significantly

In this study, the scientists found that hematopoietic stem cells and neutrophils migration depends on the megakaryocyte size and distributions. Thus, these simulations suggest that megakaryocytes play an important role in cell migration even if not migrating themselves.

Instead, the large megakaryocytes represent passive obstacles, and thus significantly influence migration of other cells such as hematopoietic stem cells and neutrophils in the bone marrow. Indeed, intravital microscopy confirmed that neutrophil mobility was reduced in platelet-depleted mice where megakaryocyte volumes are increased (see Figure 2).

This study showcases how the combination of advanced imaging approaches in combination with computational simulations can sharpen this hypothesis. Heinze says, “For simulations, grids and spheres do not sufficiently represent the complexity of the vasculature and its cells. In contrast, our image-derived templates are suitable and thus highly superior, as they reflect the physiological architecture in the bone very well.”

"This study points to the importance of biomechanical properties of the bone marrow environment in regulating cell motility, a factor which has so far not been appreciated well. Our data clearly show that volumetric analysis of the number and localization of megakaryocytes provides additional information that sharpens our picture of the bone marrow dynamics and mechanisms,” Stegner explains.

The computational tool can not only support 3D studies of dynamic cell behavior, but also help to focus or reduce animal experiments when hypotheses can be tested computationally. Beyond bone and blood research, the method can be used for any organ or tissue to interrogate dynamic maps of selected cell types and structures in health and disease.

Funding
This work is funded by the TRR-SFB240 and the Rudolf Virchow Center for Experimental Biomedicine at the University of Würzburg.

Dr. Daniela Diefenbacher (Press Office, Rudolf Virchow Center, University of Würzburg)
Tel. 0931 3188631, daniela.diefenbacher@uni-wuerzburg.de

Wissenschaftliche Ansprechpartner:

Prof. Dr. Katrin Heinze has been head of a research group at the Rudolf Virchow Center for Experimental Biomedicine at the University of Würzburg since 2011. Since 2017 she is University Professor of Molecular Microscopy.
Tel. +49 (0)931 31 84214, katrin.heinze@virchow.uni-wuerzburg.de

Dr. David Stegner is a group leader at the Institute of Experimental Biomedicine – Chair I. He utilizes advanced imaging modalities to understand the role of platelets in thrombo-inflammation.
Tel. +49 (0)931 31-80419, stegner@virchow.uni-wuerzburg.de

Originalpublikation:

Gorelashvili MG, Angay O, Hemmen K, Klaus V, Stegner D, Heinze KG. Megakaryocyte volume modulates bone marrow niche properties and cell migration dynamics. Haematologica. 2019 Jun 27. doi: 10.3324/haematol.2018.202010. [Epub ahead of print]

Weitere Informationen:

https://www.uni-wuerzburg.de/en/rvz/rvz-news/single/news/megakaryocytes-act-as-b...

Dr. Daniela Diefenbacher | idw - Informationsdienst Wissenschaft

More articles from Life Sciences:

nachricht Study reveals profound patterns in globally important algae
21.08.2019 | Bigelow Laboratory for Ocean Sciences

nachricht Intestinal bacteria in type 2 diabetes: being overweight is pivotal
21.08.2019 | Exzellenzcluster Präzisionsmedizin für chronische Entzündungserkrankungen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Quantum computers to become portable

Together with the University of Innsbruck, the ETH Zurich and Interactive Fully Electrical Vehicles SRL, Infineon Austria is researching specific questions on the commercial use of quantum computers. With new innovations in design and manufacturing, the partners from universities and industry want to develop affordable components for quantum computers.

Ion traps have proven to be a very successful technology for the control and manipulation of quantum particles. Today, they form the heart of the first...

Im Focus: Towards an 'orrery' for quantum gauge theory

Experimental progress towards engineering quantized gauge fields coupled to ultracold matter promises a versatile platform to tackle problems ranging from condensed-matter to high-energy physics

The interaction between fields and matter is a recurring theme throughout physics. Classical cases such as the trajectories of one celestial body moving in the...

Im Focus: A miniature stretchable pump for the next generation of soft robots

Soft robots have a distinct advantage over their rigid forebears: they can adapt to complex environments, handle fragile objects and interact safely with humans. Made from silicone, rubber or other stretchable polymers, they are ideal for use in rehabilitation exoskeletons and robotic clothing. Soft bio-inspired robots could one day be deployed to explore remote or dangerous environments.

Most soft robots are actuated by rigid, noisy pumps that push fluids into the machines' moving parts. Because they are connected to these bulky pumps by tubes,...

Im Focus: Vehicle Emissions: New sensor technology to improve air quality in cities

Researchers at TU Graz are working together with European partners on new possibilities of measuring vehicle emissions.

Today, air pollution is one of the biggest challenges facing European cities. As part of the Horizon 2020 research project CARES (City Air Remote Emission...

Im Focus: Self healing robots that "feel pain"

Over the next three years, researchers from the Vrije Universiteit Brussel, University of Cambridge, École Supérieure de Physique et de Chimie Industrielles de la ville de Paris (ESPCI-Paris) and Empa will be working together with the Dutch Polymer manufacturer SupraPolix on the next generation of robots: (soft) robots that ‘feel pain’ and heal themselves. The partners can count on 3 million Euro in support from the European Commission.

Soon robots will not only be found in factories and laboratories, but will be assisting us in our immediate environment. They will help us in the household, to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

The power of thought – the key to success: CYBATHLON BCI Series 2019

16.08.2019 | Event News

4th Hybrid Materials and Structures 2020 28 - 29 April 2020, Karlsruhe, Germany

14.08.2019 | Event News

What will the digital city of the future look like? City Science Summit on 1st and 2nd October 2019 in Hamburg

12.08.2019 | Event News

 
Latest News

An Ice Age savannah corridor let large mammals spread across Southeast Asia

22.08.2019 | Earth Sciences

Protein-transport discovery may help define new strategies for treating eye disease

22.08.2019 | Health and Medicine

Boreal forest fires could release deep soil carbon

22.08.2019 | Earth Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>