Stem cells for GVHD
Mesenchymal stem cells are being trialled as a potential treatment
for graft-versus-
transplantation.
Kate McDonald 28/03/2008 15:49:15
Graft-versus-
complications of allogeneic haemopoietic stem cell transplantation,
in which T cells in the graft begin to attack several of the host's
organs, especially the skin, the gut and the liver.
Treatment for the condition is usually with steroids, especially
prednisone and cyclosporine, but in the more acute cases patients do
not respond. Mortality for the most severe grade of GVHD is over 90
per cent.
In 2004, Professor Katarina Le Blanc from the division of clinical
immunology at the Karolinska Institute in Sweden and colleagues
published a case history in The Lancet outlining the use of
mesenchymal stem cells to treat acute or steroid-refractory graft-
versus-host disease.
Since then, a number of trials have been held throughout the world to
explore this novel therapy, including a small trial at the Royal
Adelaide Hospital under the direction of senior consultant
haematologist Dr Ian Lewis.
In addition to his work as a consultant, Lewis runs the Therapeutic
Products Facility at the Institute of Medical and Veterinary Science
(IMVS), a cell processing facility licensed by the TGA to produce
cellular therapeutic products such as haemopoietic cells for
transplantation, skin cells for burns patients and mesenchymal stem
cells.
He works alongside such well-known mesenchymal stem cell researchers
as Drs Stan Gronthos and Andrew Zannettino; while the latter study
the potential of MSCs in tissue repair and regeneration, Lewis is
looking at them for a different purpose completely.
No one is quite sure of the exact mechanism, but MSCs are thought to
suppress most immune responses, Lewis says. They appear to have both
immuno-modulatory and anti-inflammatory effects, but again no one is
quite sure why.
"In terms of laboratory tests they have been shown to inhibit
different aspects of the immune response, such as T cell responses,
they inhibit cytokine production and they also inhibit dendritic
cells," he says. "They seem to interact with a lot of cells in the
immune system. What actually happens in humans is not known."
So far, four Adelaide patients, all with steroid-refractory GVHD,
have been treated with a mesenchymal stem cell infusion and three
have responded, Lewis says. It is very early days yet, but this small
trial, part of the multi-institutional Le Blanc-led trial, is raising
a great deal of interest.
In addition to a potential treatment, recent studies have looked at
using MSCs as a prophylaxis for GVHD. Lewis says the rationale for
using MSCs as a prophylactic agent is fairly sound but a large study
is required to judge its efficacy.
In the meantime, US biotech Osiris Therapeutics, which is also
exploring MSCs in bone and tissue repair, is carrying out a Phase III
trial of its investigational therapy Prochymal for steroid-refractory
GVHD. 240 patients are being enrolled in the study following very
promising Phase II results, in which 94 per cent of evaluable
patients had a response and 74 per cent achieved a complete response.
More about Royal Adelaide Hospital
http://www.biotechn
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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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