Study identifies molecule essential for proper localization of blood stem cells
Result supports interaction between bone formation and production of blood, immune cells
Scientists at the Massachusetts General Hospital (MGH) Center for Regenerative Medicine and the Harvard Stem Cell Institute (HCSI) have defined a molecule that dictates how blood stem cells travel to the bone marrow and establish blood and immune cell production. The discovery may help improve bone marrow stem cell transplantation and the treatment of several blood disorders.
"This is another remarkable example of how bone and bone marrow interact. A receptor known to participate in the bodys regulation of calcium and bone also is critical for stem cells to engraft in the bone marrow and regenerate blood and immune cells," says David Scadden, MD, director of the MGH Center for Regenerative Medicine and co-director of the HSCI. "It reminds us how tissues interact and how looking closely at where stem cells reside may tell us a lot about how to manipulate them." Scadden is senior author of the report, which will be published in the journal Nature and has received early online release.
Hematopoietic or blood stem cells are critical to the daily production of over 10 billion blood cells and are the basis for bone marrow transplant therapy for cancer. Rare and difficult to identify, these cells are extremely powerful at regenerating blood and immune cells but only if they travel to the proper location when introduced into the body. Typically the cells are infused into a vein, and they find their way to the bone marrow through a process that depends on largely unknown molecules.
Within the bone marrow cavity, stem cells are usually found in the outer layer close to the inner surface of the bone. Since the process of remodeling bone takes place in the adjacent bone tissue and because studies by Scaddens group and others have shown that bone-forming osteoblast cells are essential to the regulation of the stem cell environment, it seemed probable that fundamental interactions exist between the processes of bone formation and stem cell development. As increased extracellular calcium is required for bone formation, the researchers theorized that a molecule called the calcium-sensing receptor (CaR), present on many cells, might be key to the localization of blood stem cells.
To test their theory, the researchers first verified the presence of CaR on primitive marrow cells taken from normal mice. They then ran several experiments using transgenic mice that do not produce the CaR protein and found that, while many types of marrow and adjacent bone cells were present in normal proportions, levels of blood stem cells were very low in the marrow cavities of the transgenic mice. Other experiments showed that the absence of other cell-surface molecules did not affect the numbers of stem cells in the marrow.
Examination of the spleens and the blood of the transgenic mice showed that the numbers of primitive blood stem cells were significantly elevated in those areas, indicating that the absence of CaR did not affect the production of stem cells by the fetal liver. In a group of normal mice that received radiation at doses that would destroy the bone marrow, transplantation of fetal liver cells from mice with and without CaR allowed the animals to survive, but those who received cells from CaR-negative mice had dramatically fewer stem cells in their bone marrow. Additional experiments showed that the CaR-negative cells were unable to adhere to collagen I, an essential bone protein produced by the osteoblasts.
"Since there are already drugs available that target this receptor, we may be able to quickly adapt these findings in animals to the treatment of human patients," says Scadden, who is a professor of Medicine at Harvard Medical School.
Sue McGreevey | EurekAlert!
The most recent press releases about innovation >>>
Die letzten 5 Focus-News des innovations-reports im Überblick:
Controlling electronic current is essential to modern electronics, as data and signals are transferred by streams of electrons which are controlled at high speed. Demands on transmission speeds are also increasing as technology develops. Scientists from the Chair of Laser Physics and the Chair of Applied Physics at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) have succeeded in switching on a current with a desired direction in graphene using a single laser pulse within a femtosecond ¬¬ – a femtosecond corresponds to the millionth part of a billionth of a second. This is more than a thousand times faster compared to the most efficient transistors today.
Graphene is up to the job
At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.
Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...
Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.
A warming planet
Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.
The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...
New technique promises tunable laser devices
Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...