--Findings May Aid in Bone Marrow Transplants, Blood Diseases--
PHILADELPHIA, Aug. 5 /PRNewswire-USNewswire/ -- New research sheds
light on the biological events by which stem cells in the bone marrow
develop into the broad variety of cells that circulate in the blood. The
findings may help improve the success of bone marrow transplants and
develop better treatments for life-threatening blood diseases.
"As we better understand the biological pathways that regulate the
growth of stem cells, we may identify new approaches for treating blood
disorders," said study leader Wei Tong, Ph.D., a hematology researcher at
The Children's Hospital of Philadelphia. Her study appeared online July 10
in the Journal of Clinical Investigation.
Hematopoietic stem cells (HSCs) develop into all types of blood cells:
red blood cells, white blood cells, platelets, and immune cells. HSCs, like
other stem cells, have the ability to self-renew: each can give rise to
more mature, developed cells with more specific functions, as well as a new
stem cell. (Everyone carries HSCs in their bone marrow, unlike embryonic
stem cells, which exist only in embryos.)
In her study, conducted in mice, Tong focused on a protein called Lnk
that helps control HSC expansion. When a growth factor in the blood called
thrombopoietin (TPO) acts on its cell receptor, it triggers signals along a
pathway that includes another protein, JAK2. JAK2, in turn, causes stem
cells to increase their numbers.
Tong's group and others previously found that Lnk is a negative
regulator for HSCs, acting as a brake on stem cell expansion. In the
current study, they found that mice genetically engineered to lack the Lnk
protein had 10 times the normal amount of HSCs in their bone marrow.
Without Lnk to directly interact with JAK2 and inhibit its activity, TPO
made stem cell production go into overdrive.
However, there was an unexpected potential benefit -- the expanded
population of stem cells had a higher proportion of quiescent cells, those
in a resting stage in the cell cycle. Quiescent stem cells, said Tong, are
more likely to succeed in a recipient when they are used in bone marrow
transplantation.
Although much research remains to be done, added Tong, other
researchers might build on this knowledge to manipulate HSCs for more
effective bone marrow transplants for cancer patients after high dose
chemotherapy or radiotherapy and treatments for particular blood disorders.
Aplastic anemia, severe combined immunodeficiency and hemoglobin disorders,
for example, involve deficiencies of specific immune cells in the blood.
Using a drug to inhibit Lnk could potentially produce larger numbers of
HSCs for a successful bone marrow transplant.
Myeloproliferative disorders (MPDs), on the other hand, entail the
opposite danger -- a sometimes-fatal overproduction of certain bone marrow
cells. Clinicians might use Tong's research on Lnk and its associated
signaling pathway to curtail stem cell production and control MPDs.
The National Cancer Institute, part of the National Institutes of
Health, supported Tong's research, with additional grant funding from the
McCabe Foundation and CHOP Institutional Development Fund. Tong's
co-authors were Alexey Bersenev, Chao Wu, and Joanna Balcerek, all of the
Division of Hematology at The Children's Hospital of Philadelphia.
About The Children's Hospital of Philadelphia: The Children's Hospital
of Philadelphia was founded in 1855 as the nation's first pediatric
hospital. Through its long-standing commitment to providing exceptional
patient care, training new generations of pediatric healthcare
professionals and pioneering major research initiatives, Children's
Hospital has fostered many discoveries that have benefited children
worldwide. Its pediatric research program is among the largest in the
country, ranking third in National Institutes of Health funding. In
addition, its unique family-centered care and public service programs have
brought the 430-bed hospital recognition as a leading advocate for children
and adolescents. For more information, visit http://www.chop.edu.
Contact: Ashley Moore
The Children's Hospital of Philadelphia
Phone: (267) 426-6071
mooreA1@email.chop.edu
SOURCE The Children's Hospital of Philadelphia
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Related links:
http://www.chop.edu
CONTACT:
Ashley Moore of The Children's Hospital of
Philadelphia, +1-267-426-6071, mooreA1@email.chop.edu
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