Functional Immune System Can Be Derived From Embryonic Stem Cells,
Preliminary Study Finds
ScienceDaily (Feb. 13, 2008) — 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.
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 a grant from NIH/NHLBI, a VA Merit
Review, and a grant from the Roche Organ Transplantation Research
Foundation.
Adapted from materials provided by American Society of Hematology.
Need to cite this story in your essay, paper, or report? Use one of
the following formats:
APA
MLA American Society of Hematology (2008, February 13). Functional
Immune System Can Be Derived From Embryonic Stem Cells, Preliminary
Study Finds. ScienceDaily. Retrieved February 13, 2008, from
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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