Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bone cells help call the shots for the blood’s stem cells within

23.10.2003


Molecular partners jagged and notch are key; a new role for the osteoblast



Just as oak barrels don’t simply hold fine wine but also play a vital role in its aging and development, scientists have discovered that bones nurture and control blood development in the bone marrow within to a profound extent.

In some sense the finding by scientists at the University of Rochester Medical Center, Harvard Medical School and Massachusetts General Hospital may not seem startling – after all, it’s long been known that the bone marrow that is the source of all our blood cells is in the center of our longest bones. But the team’s paper in the Oct. 23 issue of the journal Nature is the first to pinpoint the role of bone forming cells in controlling the expansion of blood-forming stem cells, and to identify a way to multiply such cells without pushing them along toward their ultimate cell fate.


The finding could be important for bone-marrow-transplant patients, for whom a limit in stem cells often makes the procedure more dangerous if not impossible. By exploiting their knowledge of the bone’s role in the creation of blood cells, the team was able to create mice that were nearly four times as likely to survive a difficult transplant as other mice. The bone marrows of the treated mice looked much healthier and were more densely packed with blood cells.

"This started as a rather improbable project, a side project that became more and more interesting as we made our findings," says Laura Calvi, M.D., of the University of Rochester Medical Center, who is the first author and an endocrinologist in the Department of Medicine. "It’s especially exciting because the compound we used is already known to work safely in people, so we can start looking quickly to see whether this strategy will work in people too."

Calvi began the work when she was a physician at Massachusetts General Hospital. A physician who specializes in treating patients with osteoporosis, she was curious about the workings of parathyroid hormone, a molecule long known as an important regulator of bone metabolism. A modified form of the compound was approved last year as the medication Forteo for the treatment of osteoporosis.

Calvi had been studying in the laboratory a genetically altered strain of mice whose bodies behaved as if there were a steady stream of the hormone – in other words, the hormone’s receptor was always activated in these mice, but only in bone-building cells known as osteoblasts, nowhere else. To understand whether modifying the bone forming cells affected the neighboring hematopoietic cells, she began collaborating with David Scadden, M.D., a hematologist at Massachusetts General with a specific interest in hematopoietic stem cell regulation.

The team found the hormone doubles the bone marrow’s output of blood-forming stem cells known as hematopoietic stem cells, from which all our blood cells originate.

The scientists also discovered that bone-building osteoblasts are key to the process, not just giving structure to bone but also affecting the formation of blood cells within. While it was known that parathyroid hormone boosts the numbers of osteoblasts, the scientists pinpointed a molecular signaling system between osteoblasts and stem cells that governs the formation of the stem cells.

"Currently there are medications to expand stem cells, but they cause the cells to differentiate also," says Calvi. "There’s not really much you can do to expand the hematopoietic stem cell population. It turns out that it’s the osteoblast, right in the bone, that is able to do that."

The ability to expand stem cells would be especially welcome for transplant patients, says Jane Liesveld, M.D., clinical director of the Leukemia, Blood and Marrow Transplant Program at the James P. Wilmot Cancer Center. Sometimes patients or their transplant donors can’t produce enough stem cells, making them ineligible for the procedure, which is sometimes a patient’s best chance for survival.

Calvi and Scadden’s team pinpointed molecular signals known as "Jagged-1" and "Notch" as the key players that bring osteoblasts and stem cells together. The team found that parathyroid hormone not only boosts the number of osteoblasts but also the amount of Jagged-1 on those cells, making them more likely to interact with the Notch molecule on stem cells and spur their expansion.

Notch is well known to stem cell researchers such as hematologist Laurie Milner, M.D., associate professor of Pediatrics and Medical Oncology in the university’s Aab Institute of Biomedical Sciences and an author of the Nature paper. She was one of the first people to discover the importance of Notch in stem cells, identifying the molecule as one that helps direct immature blood cells decide their fate. It’s Notch that allows a fixed number of stem cells to serve as the font of blood cells that will last a lifetime.

Milner says while there has been some evidence of the involvement of Jagged and Notch in the stem cell process, it wasn’t known which of the body’s cells besides the stem cells were involved.

"For the most part, hematopoietic stem cells researchers haven’t thought that much about osteoblasts, though they’re in the bone marrow right next to the blood cells that are developing," says Milner.

Calvi attributes her interest in looking beyond the traditional boundaries of bone researchers partly to her constant contact with a hematologist, her husband Jonathan Friedberg, M.D.

"I look at bone as a bone biologist would," says Calvi. "The osteoblasts provide support and maintain structure. He looks at bone as a source for bone marrow. We had a lot of interesting discussions. Why is it that blood cells are produced in the bone? Is it simply because the bone can provide the space, or is there more to it?"

While working on the project, Calvi moved to Rochester from Harvard in the summer of 2002; she credits a talk by a Rochester colleague, hematologist James Palis, on the origins of blood cells, with putting her on the trail of Notch and Jagged.

"Sometimes you just need to be exposed to something that is foreign, to open your eyes to understand what you’ve been looking at," Calvi says.

Calvi did the work with funding from the National Institute of Diabetes and Digestive and Kidney Diseases. The research was also funded by the American Society of Hematology, the Doris Duke Foundation, and the Burroughs Wellcome Fund.

In addition to Calvi and Milner, the Rochester authors include technician Jonathan Weber. Authors from Harvard Medical School include M.C. Knight, E. Schipani, P. Divieti, F.R. Bringhurst, H.M. Kronenberg; authors from Massachusetts General Hospital Cancer Center, besides Scadden, were G.B. Adams, K.W. Weibrecht, D.P. Olson, and R.P. Martin.


###

Tom Rickey | EurekAlert!
Further information:
http://www.urmc.rochester.edu/

More articles from Health and Medicine:

nachricht 'Exciting' discovery on path to develop new type of vaccine to treat global viruses
18.09.2017 | University of Southampton

nachricht A new approach to high insulin levels
18.09.2017 | Schweizerischer Nationalfonds SNF

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

Im Focus: Fast, convenient & standardized: New lab innovation for automated tissue engineering & drug

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems Holding GmbH about commercial use of a multi-well tissue plate for automated and reliable tissue engineering & drug testing.

MBM ScienceBridge GmbH successfully negotiated a license agreement between University Medical Center Göttingen (UMG) and the biotech company Tissue Systems...

Im Focus: Silencing bacteria

HZI researchers pave the way for new agents that render hospital pathogens mute

Pathogenic bacteria are becoming resistant to common antibiotics to an ever increasing degree. One of the most difficult germs is Pseudomonas aeruginosa, a...

Im Focus: Artificial Enzymes for Hydrogen Conversion

Scientists from the MPI for Chemical Energy Conversion report in the first issue of the new journal JOULE.

Cell Press has just released the first issue of Joule, a new journal dedicated to sustainable energy research. In this issue James Birrell, Olaf Rüdiger,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

New quantum phenomena in graphene superlattices

19.09.2017 | Physics and Astronomy

A simple additive to improve film quality

19.09.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>