Duke research team identifies a potent growth factor for blood stem cells
Duke Medicine researchers studying the interaction of blood stem cells and the niche where they reside have identified a protein that may be a long-sought growth factor for blood stem cells.
The protein is called pleiotrophin, and is produced by cells that line the blood vessels in bone marrow. In mouse studies conducted by the Duke researchers, the protein helps transplanted blood stem cells locate to the bone marrow, where they produce mature red and white blood cells in the body.
The finding, reported in the Oct. 18, 2012, issue of the journal Cell Reports, could lead to new treatments that speed recovery of healthy blood levels for patients receiving chemotherapy or undergoing bone marrow and cord blood transplants.
"Our hypothesis is that pleitrophin has the potential to promote blood stem cell growth in the manner that erythropoietin stimulates red blood cell precursors," said principal investigator John Chute, M.D., professor of Medicine, Pharmacology & Cancer Biology.
Many patients have benefitted from the discovery of erythropoietin (EPO), which stimulates the body to produce mature red blood cells. A synthetic form of EPO is commonly used to treat patients with anemia. Similarly, granulocyte colony stimulating factor (Neupogen), a growth factor for white blood cells, is used to remedy low white blood cell counts that often result from chemotherapy or radiation treatments for cancer.
"A principle objective in hematology for several decades is to identify a growth factor capable of promoting blood stem cells to grow without differentiating," Chute said.
Pleiotrophin may be one such growth factor. Pleiotrophin, which means "many forms," appears to make blood stem cells grow and promote production of all the mature blood lineages that are derived from the blood stem cell. Previously, Chute and his colleagues had shown that treatment with pleiotrophin promoted the expansion of mouse and human blood stems cells in cultures that were capable of engrafting in transplanted mice.
In the new research, lead researcher Heather Himburg, Ph.D., assistant professor of medicine, and Chute's research team showed that cells lining blood vessels in the bone marrow produce pleiotrophin, where it acts as a homing device to attract and retain stem cells. The researchers then demonstrated that genetically engineered mice missing the gene encoding pleiotrophin had decreased numbers of stem cells in their bone marrow, and had difficulty making new blood cells if depleted.
When the researchers treated normal mice with an anti-pleiotrophin antibody, it had the surprising effect of causing existing blood stem cells to be released from bone marrow and enter the blood stream. The finding was particularly exciting to the researchers, as the effect was similar to that observed when granulocyte-colony stimulating factor is used clinically to mobilize stem cells from a donor's bone marrow for use in blood stem cell transplants.
"The discoveries together suggest two possible therapeutic uses," said Chute. "Treatment with pleiotrophin may prove useful in helping patients more quickly regenerate their own blood forming cells after chemotherapy or bone marrow transplant. Second, anti-pleiotrophin antibodies may be useful in mobilizing stem cells to the peripheral blood."
The researchers are planning additional studies to understand how the homing system works and how pleiotrophin interacts with other growth factors to regulate blood stem cell function in the body. Given that some prior studies have suggested that pleiotrophin can promote cancer cell growth, human safety studies will be crucial, Chute said.
Journal reference: Cell Reports
Provided by Duke University Medical Center
- Newly identified growth factor promotes stem cell growth, regeneration Mar 21, 2010 | not rated yet | 0
- Molecule dictates how stem cells travel Jan 14, 2006 | not rated yet | 0
- Study identifies gene involved in blood stem cell replication, movement Apr 09, 2008 | not rated yet | 0
- Protein key to control, growth of blood cells Aug 13, 2008 | not rated yet | 0
- No survival advantage with peripheral blood stem cells versus bone marrow Oct 19, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
2 hours ago Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
22 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
Every day, their baby stopped breathing, his collapsed bronchus blocking the crucial flow of air to his lungs. April and Bryan Gionfriddo watched helplessly, just praying that somehow the dire predictions ...
Medical research 12 hours ago | 5 / 5 (2) | 0
The human gut is loaded with commensal bacteria – "good" microbes that, among other functions, help the body digest food. The gastrointestinal tract contains literally trillions of such cells, and yet the ...
Medical research 16 hours ago | 5 / 5 (3) | 0 |
Swiss scientists reveal the mechanism responsible for aging hidden deep within mitochondria—and dramatically slow it down in worms by administering antibiotics to the young.
Medical research 16 hours ago | 4.9 / 5 (8) | 0 |
On May 22, JoVE will publish details of a technique to measure the health of human genetic material in relation to a patient's age. The method is demonstrated by the laboratory of Dr. Gil Atzmon at New York's Albert Einste ...
Medical research 20 hours ago | not rated yet | 0
(Medical Xpress)—Scientists supported by the National Institutes of Health have a new theory as to why a woman's fertility declines after her mid-30s. They also suggest an approach that might help slow ...
Medical research 21 hours ago | not rated yet | 0 |
Researchers from Queen Mary, University of London have led the largest sequencing study of human disease to date, investigating the genetic basis of six autoimmune diseases.
16 hours ago | 4.7 / 5 (3) | 0 |
Until now, little was scientifically known about the human potential to cultivate compassion—the emotional state of caring for people who are suffering in a way that motivates altruistic behavior.
13 hours ago | 5 / 5 (2) | 2 |
(HealthDay)—Migraines and depression can each cause a great deal of suffering, but new research indicates the combination of the two may be linked to something else entirely—a smaller brain.
13 hours ago | 4 / 5 (2) | 0 |
Existing research shows that bicyclists who wear helmets have an 88 percent lower risk of brain injury, but researchers at Boston Children's Hospital found that simply having bicycle helmet laws in place showed a 20 percent ...
5 hours ago | not rated yet | 0
A new approach for immunizing against influenza elicited a more potent immune response and broader protection than the currently licensed seasonal influenza vaccines when tested in mice and ferrets. The vaccine ...
14 hours ago | not rated yet | 0 |
In a series of lab experiments designed to unravel the workings of a key enzyme widely considered a possible trigger of rheumatoid arthritis, researchers at Johns Hopkins have found that in the most severe ...
15 hours ago | 5 / 5 (1) | 0 |