Brief description of NeuroStemcell by Work Packages
The work plan is structured into six closely linked workpackages (WPs)
Work Package 1
The purpose of WP1 is to generate transplantable mesencephalic dopamine (mesDA) and striatal GABAergic neurons from established embryonic and neural stem cell lines in numbers that are clinically relevant.
Work Package 2
The purpose of WP2 is To characterize and improve the ability of the cells developed in WP1, to survive, grow, and differentiate in vivo into fully mature mesDA and striatal GABAergic neurons, in the absence of tumour formation or adverse immunological/inflammatory host response.
Work Package 3
In WP3 the rodent and human cell lines that fulfill the criteria of progenitors of DA and striatal GABAergic neurons in vitro (as determined in WP1) and that are able to survive and differentiate properly in vivo in the absence of tumour formation or other adverse effects (as determined in WP2) will be studied for their functional properties and ability to affect long-term behavioural recovery after transplantation into PD and HD models. The PIs involved in this WP have already available validated cell lines (ES, NS, iPS and expanded VMN) that will be used in the initial part of the work.
Work Package 4
In WP4 we will employ state-of-the art Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) imaging techniques to monitor, non-invasively, the survival, growth and development of the grafted cells, their functional impact on the host brain, and their ability to restore neurotransmission in rat PD and HD models. In addition, work will be performed to validate the use of PET imaging to pick up potential adverse reactions associated with immune or inflammatory responses to the grafted cells. The goal of the studies included in WP4 is to identify those imaging procedures that are readily available and can be included as non-invasive assessment tools in the clinical transplantation protocols.
Work Package 5
WP5 is focused on the manufacturing processes and safety aspects of cell production for for PD and HD cell therapies, including establishment of criteria for defining the suitability of the cell lines for clinical application, stability over long term passage, media development, and scale-up of manufacturing under GMP conditions.
Work Package 6
WP6 will address the clinical, societal, regulatory and ethical issues that are associated with the development towards clinical use. Throughout the planned project, WP6 will interact closely with all the other WPs as well as with external expertise to reach the different objectives.
