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A Functional Immune System Can Be Derived From Embryonic Stem Cells, Preliminary Study Finds
A new study demonstrates
for the first time that embryonic stem cells can be used to create
functional immune system blood cells, a finding which is an important step
in the utilization of embryonic stem cells as an alternative source of
cells for bone marrow transplantation. This hopeful news for patients with
severe blood and immune disorders, who need these transplants for
treatment, was prepublished online in Blood, the official journal of the
American Society of Hematology.
Embryonic stem cells (ESCs) are being intensely investigated as a
renewable source of primitive cells theoretically able to regenerate all
tissues and organs. The use of ESC-derived blood-forming cells may have an
important advantage over traditional transplants that use bone marrow,
umbilical cord blood, and peripheral blood from donors. The antigens on the
surface of donated cells must be compatible (determined by a method called
HLA matching) with those of the patient to prevent rejection. The use of
embryonic stem cells, which have low levels of these antigens and may
therefore be less likely to provoke a defensive reaction by the patient's
body, may allow patients who can't find suitable HLA-matched donors to
receive transplants.
Previous studies have shown that mouse ESCs can be coaxed to form
blood-forming hematopoietic cells by introducing a protein called HOXB4,
known for its unique ability to greatly enhance cell proliferation, into
them. These cells could then be transplanted into mice whose own marrow had
been destroyed by radiation, rescuing their marrow function and beginning
to produce necessary blood cells. However, previous studies have not
investigated whether ESC-derived bone marrow in these mice could regenerate
normal immune function -- in particular, if they could allow the mice to
respond to viruses or vaccines. Because fetuses have no need for a
functional immune system as they are protected from the environment while
in the womb, it was unclear if ESC-derived marrow would recreate an immune
system at all or just very slowly.
In this study, a team of scientists from Iowa, Taiwan, and Germany used
HOXB4-containing ESCs to engraft the bone marrow and rescue mice that
genetically lacked any immune system and had been irradiated to destroy
their bone marrow. Only cells containing HOXB4 were able to engraft, rescue
the mice, and produce blood cells long term. These engrafted cells were
shown to be derived from the transplanted ESC-derived cells.
To determine if these transplants were able to rebuild the defunct
immune system, the scientists injected the mice with LCMV, a common rodent
virus, and watched for T-cell activity, a sign that the body was defending
itself against the infection. Although the number of T cells generated by
the new hematopoietic cells was low, they were able to respond effectively
to the virus. In addition, the transplanted hematopoietic cells were also
able to produce B cells and other defensive cells called antigen-presenting
cells, which have a role in signaling T cells to action. They also tested
the ability of the mice to respond to vaccination and demonstrated the
induction of specific immune cells. Although the level of immune response
was not what is seen in normal adult mice after exposure to the virus or
vaccine, it was measurable and effective.
The study was also encouraging in that none of the 70 transplanted mice
followed for more than 200 days developed any tumors -- another concern
when using ESCs for tissue regeneration.
"These results show, for the first time, that functional white blood
cells, the key players in the body's immune system, can be successfully
derived from embryonic stem cells expressing HOXB4," said lead study author
Nicholas Zavazava, MD, PhD, Professor of Internal Medicine and Director of
Transplant Research at the University of Iowa Hospitals and Clinics in Iowa
City and Staff Physician at the Iowa City VA Medical Center. "Therefore,
we're hopeful that these exciting findings are the first step toward new,
improved therapies for patients."
This study was supported by grant RO1 HL073015 (NIH/NHLBI), a VA Merit
Review, and a grant from the Roche Organ Transplantation Research
Foundation (ROTRF).
The American Society of Hematology (http://www.hematology.org) is the
world's largest professional society concerned with the causes and
treatment of blood disorders. Its mission is to further the understanding,
diagnosis, treatment, and prevention of disorders affecting blood, bone
marrow, and the immunologic, hemostatic, and vascular systems, by promoting
research, clinical care, education, training, and advocacy in hematology.
Blood, the official journal of the American Society of Hematology, is
the most cited peer-reviewed publication in the field. Blood is issued to
Society members and other subscribers twice per month, available in print
and online at http://www.bloodjournal.org.
American Society of Hematology
http://www.hematology.org
Un sistem imunitar funcþional pot fi derivate din celule stem embrionare, constatã studiul preliminar - A Functional Immune System Can Be Derived From Embryonic Stem Cells, Preliminary Study Finds - articole medicale engleza - startsanatate