The finding, published online in May in the journal Blood, improves understanding of how such stem cells work and could have implications for the future of bone marrow and peripheral blood progenitor cell transplants, which are used in the treatment of a variety of illnesses – including leukemia, lymphoma and immunodeficiency.
The success of these transplants depends on the ability of intravenously infused blood-forming stem cells, which normally reside predominantly in the bone marrow, to accurately and efficiently migrate from the blood to the marrow of the transplant recipient and, once there, to repopulate their pool of mature blood cells.
“In normal individuals, blood-forming stem cells continually seed the production of all cells in the adult blood system. Appropriate regulation of stem cell activity is essential for maintaining this normal cell replacement, and for supporting repair of the blood system after injury,” said lead author Amy J. Wagers, Ph.D., Principal Investigator in the Joslin Section on Developmental and Stem Cell Biology, principal faculty member at the Harvard Stem Cell Institute and Assistant Professor of Stem Cell and Regenerative Biology at Harvard University.
The signals that regulate stem cells remain largely mysterious, but some have been proposed to emanate from specialized cells in the bone marrow environment which form a supportive “stem cell niche” to communicate physiologically relevant signals to stem cells.
A number of earlier studies had implicated bone-lining osteoblasts as important “niche cells.” However, these earlier studies were complicated by the presence of other cell types within the bone marrow. As a result, whether osteoblasts in particular could modulate blood-forming stem cell activity remained controversial.
To clarify this issue, Wagers and co-author Shane R. Mayack, Ph.D., Research Fellow in the Joslin Section on Development and Stem Cell Biology, developed a strategy to isolate osteoblasts and then exposed these osteoblasts to bone marrow stem and progenitor cells in vitro to test their ability to alter stem cell proliferation and function.
“The idea was to deconstruct the complexity of the marrow environment to find out whether osteoblasts alone were sufficient to regulate stem cell activity,” said Wagers.
In their experiment, the researchers took osteoblasts from normal mice and from mice treated with drugs designed to cause stem cells to proliferate and migrate – a process known as “mobilization.” They then exposed the isolated osteoblasts to bone marrow progenitor cells from normal mice in vitro.
The bone marrow cells exposed to the osteoblasts taken from the treated mice proliferated rapidly, while those from untreated mice were inhibited from replicating.
According to Wagers, this effect demonstrates that the osteoblast cells are capable of communicating to the stem cells the physiological signals provided by the drugs.
“It demonstrates that osteoblasts act as functional niche cells capable of directly regulating stem cell activity,” she said. “This work provides mechanistic insight into the common process of stem cell mobilization and makes available a new way to discover novel pathways that regulate the expansion of hematopoietic stem cells.”
“Additionally, this study establishes a new paradigm for examining more generally how ‘support cells’ in the body influence stem cell activity,” she said.
The new finding also provides an opportunity to study potential changes in niche cells that may contribute to diseases such as leukemia or bone marrow failure, said Wagers.
According to Wagers, future studies will seek to identify the molecular factors necessary for the communication between the osteoblasts and stem cells and to try and understand how changes in that communication system may play a role in the development of disease.
The work was supported in part by grants from the Smith Family Medical Foundation, Paul F. Glenn Laboratories, a Burroughs Wellcome Fund Career Award and the National Institutes of Health.About Joslin Diabetes Center
Kira Jastive | newswise
Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute
'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)
Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.
This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...
Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion
Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...
Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.
"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...
In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.
A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...
By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.
"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...
14.10.2016 | Event News
14.10.2016 | Event News
12.10.2016 | Event News
27.10.2016 | Materials Sciences
27.10.2016 | Physics and Astronomy
27.10.2016 | Life Sciences