Children’s
Research Institute at UT Southwestern Medical Center
Media
Contact: Jeff Carlton
214-648-3404
`jeffrey.carlton@utsouthwestern.edu
DALLAS
– Jan. 25, 2012 – Scientists with the new Children’s Research Institute at
UT Southwestern Medical Center have identified the environment in which
blood-forming stem cells survive and thrive within the body, an
important step toward increasing the safety and effectiveness of bone-marrow
transplantation.
Institute
investigators led by Dr.
Sean Morrison asked which cells are responsible for the microenvironment
that nurtures haematopoietic stem cells, which produce billions of new blood
cells every day. The answer: endothelial and perivascular cells, which line
blood vessels.
“Although scientists have searched for decades to identify the stem cell home,
this is the first study to reveal the cells that are functionally responsible
for the maintenance of blood-forming stem cells in the body,” said Dr.
Morrison, director of the new institute and senior author of the study available
Jan. 26 in Nature. “This discovery will lead to the identification of
the mechanisms by which cells promote stem cell maintenance and expansion.”
Scientists
already have determined how to make large quantities of stem cells and how to
change these cells into those of the nervous system, skin and other tissues. But
they have been stymied by similar efforts to make blood-forming stem cells. A
key obstacle has been the lack of understanding about the microenvironment, or
niche, in which blood-forming stem cells reside in the body.
In
the first breakthrough from the Children’s Research Institute, Dr.
Morrison’s laboratory addressed this issue by systematically determining which
cells are the sources of stem cell factor, a protein required for the
maintenance of blood-forming stem cells. His team swapped out the mouse gene
responsible for stem cell factor with a gene from jellyfish that encodes green
fluorescent protein. The cells that glowed green were endothelial and
perivascular cells, revealing them as the creators of the niche that nurtures
healthy blood-forming stem cells.
Additional
lab work showed that blood-forming stem cells become depleted if stem cell
factor is eliminated from either endothelial or perivascular cells. Loss of stem
cell factor from both of these sources caused stem cells to virtually disappear.
The
research has implications for bone marrow and umbilical cord blood transplants,
Dr. Morrison said. If scientists can identify the remaining signals by which
perivascular cells promote the expansion of blood-forming stem cells, then they
may be able to replicate these signals in the laboratory. Doing so will make it
possible to expand blood-forming stem cells prior to transplantation into
patients, thereby increasing the safety and effectiveness of this widely used
clinical procedure.
Dr.
Morrison’s paper is the first to emerge from the Children’s Research
Institute at UT Southwestern, a pioneering venture that combines the medical
center’s research prowess with the world-class clinical expertise of
Children’s Medical Center Dallas. Under Dr. Morrison’s leadership, the
institute is focusing on research at the interface of stem cell biology, cancer,
and metabolism that has the potential to reveal new strategies for treating
disease.
The institute currently has more than 30 scientists and will eventually include
150 scientists in 15 laboratories led by UT Southwestern faculty members. Dr.
Morrison’s lab focuses on adult stem cell biology and cancers of the blood,
nervous system and skin.
The Nature paper’s first author is Dr. Lei Ding, postdoctoral research
fellow at the Children’s Research Institute and the Howard Hughes Medical
Institute. Scientists from the University of Michigan and Cold Spring Harbor
Laboratory also contributed to the study, which was supported by the HHMI
and the National
Heart, Lung and Blood Institute.
