Article

Stroke is the second leading cause of death worldwide and the most common cause
of severe disability. Neuroprotection and repair mechanisms supporting endogenous
brain plasticity are often insufficient to allow complete recovery. While
numerous neuroprotective drugs trials have failed to demonstrate benefits for
patients, they have provided interesting translational research lessons related
to neurorestorative therapy mechanisms in stroke. Stroke damage is not limited to
neurons but involve all brain cell type including the extracellular matrix in a
"glio-neurovascular niche". Targeting a range of host brain cells, biotherapies
such as growth factors and therapeutic cells, currently hold great promise as a
regenerative medical strategy for stroke. These techniques can promote both
neuroprotection and delayed neural repair through neuro-synaptogenesis,
angiogenesis, oligodendrogliogenesis, axonal sprouting and immunomodulatory
effects. Their complex mechanisms of action are interdependent and vary according
to the particular growth factor or grafted cell type. For example, while
"peripheral" stem or stromal cells can provide paracrine trophic support, neural
stem/progenitor cells (NSC) or mature neurons can act as more direct neural
replacements. With a wide therapeutic time window after stroke, biotherapies
could be used to treat many patients. However, guidelines for selecting the
optimal time window, and the best delivery routes and doses are still debated and
the answers may depend on the chosen product and its expected mechanism including
early neuroprotection, delayed neural repair, trophic systemic transient effects
or graft survival and integration. Currently, the great variety of growth
factors, cell sources and cell therapy products form a therapeutic arsenal that
is available for stroke treatment. Their effective clinical use will require
prior careful considerations regarding safety (e.g. tumorgenicity,
immunogenicity), potential efficacy, cell characterization, delivery route and in
vivo biodistribution. Bone marrow-derived cell populations such as mesenchymal
stromal/stem cells (MSC) or mononuclear cells (MNC), umbilical cord stem cells
and NSC are most investigated notably in clinical trials. Finally, we discuss
perspectives concerning potential novel biotherapies such as combinatorial
approaches (growth factor combined with cell therapy, in vitro optimization of
cell products, or co-transplantation) and the development of biomaterials, which
could be used as injectable hydrogel scaffold matrices that could protect a cell
graft or selectively deliver drugs and growth factors into the post-stroke cavity
at chronic stages. Considering the remaining questions about the best procedure
and the safety cautions, we can hope that future translational research about
biotherapies will bring more efficient treatments that will decrease post-stroke
disability for many patients.
CI - Copyright (c) 2014 Elsevier Masson SAS. All rights reserved.
AVC - plasticité - traitement

Langue : ANGLAIS