INSTITUTE Fondazione Centro San Raffaele
ADDRESS Via Olgettina 60 - 20132 Milano, Italy
The Martino lab has contributed to the field of stem cell biology demonstrating that adult and embryonic-like neural stem/precursor cells (NPCs) possess a constitutive and inducible ‘neuroprotective’ signature which makes these cells - once in vivo transplanted - capable of interacting with both blood-borne and CNS-resident immune relevant cells in order to protect from inflammatory damage, the so called ‘bystander’ effect.145 In vivo transplanted NPCs may act as therapeutic weapons not only by replacing damaged cells but also by promoting neuroprotection via the release of immunomodulatory and neurotrophic molecules, a novel concept named ‘therapeutic plasticity’.146 These results have also been substantiated by the fact that endogenous adult neural stem cells exert - releasing soluble neuroprotective molecules - a homeostatic control on CNS-resident cells.
The lab is now involved in defining the molecular and cellular - autonomous and non-autonomous - mechanism(s) sustaining the anti-inflammatory and neuroprotective effect exerted by both endogenous and transplanted NPCs using animal models of focal/acute (e.g. ischemic stroke, spinal cord injury) and chronic/multifocal inflammatory CNS disorders as well as in house established transgenic mouse models. Furthermore, pertinent to this project, the laboratory has acquired expertise in the field of induced pluripotent stem cells (iPSCs) in the mouse134,138 and human context (unpublished). Namely, reprogrammed pluripotent lines are generated from healthy and MS affected individuals and their differentiated derivatives are currently matter of active investigation from a pheno-(epi)genetic point of view.
Pertinent to the proposal, Partner 1 will contribute with murine primary cortical neuronal cultures, with a line of fetal NPC and will be in charge of distributing hiPSC lines from healthy control and MS individuals with different disease profiles (RR, PP, SP) to partners with specific expertize on differentiated hiPSCs for functional assay set up. Further, Partner 1 will be in charge of performing co-culture experiment and in vivo EAE disease modeling therapeutic trial. Collaborations with Kuhlmann and Baron lab are already on going.