STROKECELLFUSION

Cell fusion as regenerative tool for stroke treatment

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 Obiettivo del progetto (Objective)

'In the last years it has been shown that transplanted adult bone marrow derived stem cells (BMSCs) have the ability to fuse with cells of other types and restore several pathologies such as congenital liver failure and muscular dystrophy. On the nervous system, it was recently reported that bone marrow transplantation (BMT) made 24 hours after the stroke leads to a functional outcome. Cell fusion is one of the underlying mechanisms as it has been shown that it is indirectly implicated in the formation of vasculature after stroke. Thus, stroke is a pathology susceptible to be treated with this cell therapy mechanism. Despite the great potential of this mechanism of regeneration, the low frequency of fusion events, especially in the brain, has veiled and hindered the true regenerative potential of cell fusion. Therefore, the main objective of this project is to identify fusogenic factors that will increase cell fusion events to an effective level for cell therapy of neurological disorders. For this, firstly we will screen in vitro new putative fusogenic with the help of an in vitro cell fusion detection system and FACS analysis. Later, chitosan nanoparticles will be developed for the controlled release of the putative fusogenic factors. Finally, we will evaluate the in vivo efficacy of these factors trough a series of intravenous BMT co-administered with nanoparticles loaded with the selected factors in the mouse model of stroke. We will correlate an increment in the cell fusion events with the putative improvement in stroke symptoms. With this project we will improve our knowledge about adult stem cell plasticity and explore cell fusion process as a neuroregenerative process for the treatment of stroke.'

Introduzione (Teaser)

Brain ischemic stroke is the second most frequent cause of death worldwide. Transfusion of bone marrow stem cells (BMSCs) after the stroke may assist in brain function recovery.

Descrizione progetto (Article)

Recent studies in animal models of stroke demonstrated a significant effect on brain recovery when BMSC were introduced.

The possible mechanism of recovery is BMSC fusion with cells in the damaged area of the brain.

However, its regenerative potential is limited by the low frequency of fusion events, especially in the brain.The EU-funded 'Cell fusion as regenerative tool for stroke treatment' (STROKECELLFUSION) project aimed to identify the factors that will increase cell fusion events for effective cell therapy of neurological disorders.

Researchers focused on identification of new fusogenic factors and development of a nanocarrier system for their sustained and controlled delivery.Poly lactic nanoparticles (PLA NPs) were selected as a non-toxic delivery system.

Studies of PLA NPs with fluorescent labels revealed a uniform body distribution.

Cell differentiation factor interleukin-4 (IL-4) was identified and selected as a putative agent to encourage fusion using an in vitro cell fusion detection system of BMSC and neural cells.IL-4 fusion stimulation was observed in vivo in mice transplanted with BMSCs.

Pathological conditions, such as stroke, might potentiate the fusogenic effect of IL-4 due to the unique cell environment at the damaged area.STROKECELLFUSION has developed a novel delivery system to support BMSC transplantation.

This system can be applied to other neurodegenerative conditions that involve a damaged blood brain barrier and that require drugs with a controlled pharmacokinetic profile.