increases the survival of transplanted blood stem cells in patients with
life threatening blood cancers.
- Donor stem cells
tend to have a self-destructive tendency to produce tumor necrosis factor-alpha (TNF-α), which may be overproduced,
killing healthy cells.
- Etanercept is an
antibody that works by binding to tumor necrosis factor-alpha and helping the donor cells to thrive in
a medication used around the world to treat autoimmune
diseases like arthritis and psoriasis can now be used to save transplanted stem
cells from being rejected in blood cancer patients. While blood stem cell transplants
are a potential cure for life threatening blood cancers, the inability of these
cells to integrate into the hosts' bone marrow and differentiate, limits its
usage. New study by a research team at the University of British Columbia shows
that administering etanercept solves this challenge. The findings
of the study are published in Science Translation Medicine.
The Problem with Blood Stem Cell Transplants
cells ae cells that can differentiate into all types of blood cells including
white blood cells, red blood cells and platelets. However, most of the donor
stem cells come from umbilical cord blood and the derived stem
cells when transplanted do not get integrated into the recipient's bone marrow
to differentiate and produce a self-sustaining blood-forming system. Also, many
umbilical cord blood donations are too small to provide enough mass of stem
cells necessary to repopulate in a new host. Moreover, mismatched stem cell
can cause graft rejection and failure that is often fatal.
study has one reason for the lack of integration and differentiation of the
transplanted cells. The study reports that once the donor stem cells are
transplanted, some of them differentiate and have a tendency to express a
self-destructive protein called the tumor necrosis factor-alpha (TNF-α). This
is a protein that the immune system uses to fight infection. When TNF-α is
overproduced by the newly differentiated transplanted cells, the immune system
ends up attacking and killing these healthy cells.
was led by Peter Zandstra, director of UBC's new School of
Biomedical Engineering and UBC's Michael Smith Laboratories to test if existing
TNF-α blockers could help transplanted stem cells to thrive in the new host.
‘Administration of etanercept increases survival of transplanted blood stem cells in mice.’
study model used were mice with genetically weakened immune systems. Etanercept
an antibody that binds and disables
TNF-α, was administered to the mice. The drug is sold by Amgen in Canada and
Enbrel in the U.S.
weeks later, it was observed that the mice treated with etanercept had a more
diverse collection and a higher amount of blood stem cells in their bone marrow
compared to the control group.
The study results provide strong
evidence to conduct human clinical trials using etanercept or other TNF-α
blockers to determine if it has the same transplanted stem cell saving property
that was seen in mice.
- W. Wang el al., "Enhanced human hematopoietic stem and progenitor cell engraftment by blocking donor T cell-mediated TNFα signaling," Science Translational Medicine (2017).