Cancer Research - Europa

Keywords | Radiation-induced complications | adult stem cell therapy | cancer therapy |
FIRST
Further improvement of radiotherapy of
cancer through side-eff ect reduction by
application of adult stem cell therapy
Summary
Radiotherapy is the second most important treatment
modality after surgery in the treatment of cancer. At present
over 50 % of all cancer patients receive radiotherapy at
one stage in their course. Inevitably normal tissues are also
exposed to ionising radiation during radiotherapy of
tumours. This can result in organ failure and hence can
seriously limit the treatment dose. Reduction of the sideeff
ects of radiotherapy will not only increase the quality of
life after the treatment but may also result in increased
survival of cancer patients as it will allow dose escalation
to the tumour. This is true even if the most optimal physical
dose delivery (conformal therapy, protons) of radiation
is applied. Radiationinduced organ failure is mainly caused
by stem cell sterilisation, leading to a reduced reconstitution
of functional cells. The innovative vision of this project
is to reduce radiation-induced complications through stem
cell therapy. Replenishment of the depleted stem cell compartment
should allow regeneration of irradiated tissues.
A successful replacement of stem cells and subsequent
amelioration of radiation-induced complications may open
the road to completely new strategies in radiotherapy and
help combat cancer.
Problem
Many attempts have been made to attenuate radiationinduced
damage to normal tissues. Although much knowledge
has been obtained on the mechanism of radiosensitivity of
normal tissue, and the pathogenic pathways that eventually
result in loss of function, the vast majority of remedies are
either inadequate, diminish in time or have not been shown to
be selective for normal tissue only. Therefore a completely
new approach is needed. Today bone marrow transplantation
is common clinical practice. Due to new scientifi c knowledge
TREATMENT
and biotechnological developments, only recently it has
become apparent that bone marrow transplantation may rescue
other organs. Moreover, cells from certain tissues may
even repopulate the haematopoietic system. Similar fi ndings
have been reported for stem cells derived from other tissues
than bone marrow. However, tissue specifi c cells are only
available in small numbers. Therefore, bone marrow stem
cells have the largest clinical potential to be used for transplantation
into irradiated organisms or individual normal
tissues to provide the organ with suffi cient numbers of cells
necessary for regeneration.
Aim
The aim of the project is to develop and optimise techniques
to prevent radiation-induced normal tissue complications
using adult stem cell therapy. The tissues of interest will be
oral mucosa, skin, gut and salivary gland tissues. The fi rst step
will be to provide proof of principle for the impact of stem
cells on the repair of irradiated tissues.
To this end protocols for the isolation, mobilisation, and characterisation
of bone marrow derived stem cells will be
performed and developed. Specifi c targeted approaches for
transplantation of bone marrow derived stem cells will be
designed and tested.
Expected results
• Optimised protocols for isolation, generation, mobilisation,
characterisation and expansion of stem cells from
bone marrow.
• Demonstration of proof of principle for the use of bone
marrowderived stem cells to modifi cate radiation-induced
normal tissue damage in animal models.
Potential applications
The resulting scientifi c and (bio)technological knowledge and
a successful replacement of stem cells and subsequent amelioration
of radiation-induced complications may eventually
lead to new and improved cancer treatment strategies which
will profoundly increase radiotherapy treatment success.
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