title: Neural stem cell transplantation in central nervous system disorders:  from cell replacement to neuroprotection.
abstract: OBJECTIVE
  Transplantation of neural stem/precursor cells (NPCs) has been proposed as a promising therapeutic strategy in almost all neurological disorders characterized by the failure of central nervous system (CNS) endogenous repair mechanisms in restoring the tissue damage and rescuing the lost function. Nevertheless, recent evidence consistently challenges the limited view that transplantation of these cells is solely aimed at protecting the CNS from inflammatory and neurodegenerative damage through cell replacement.
  
  
  RESULTS
  Recent preclinical data confirmed that transplanted NPCs may also exert a 'bystander' neuroprotective effect and identified a series of molecules - for example, immunomodulatory substances, neurotrophic growth factors, stem cell regulators as well as guidance molecules - whose in-situ secretion by NPCs is temporally and spatially orchestrated by environmental needs. A better understanding of the molecular and cellular mechanisms sustaining this 'therapeutic plasticity' is of pivotal importance for defining crucial aspects of the bench-to-beside translation of neural stem cell therapy, that is route and timing of administration as well as the best cellular source. Further insight into those latter issues is eagerly expected from the ongoing phase I/II clinical trials, while, on the other hand, new cellular sources are being developed, mainly by exploiting the new possibilities offered by cellular reprogramming.
  
  
  CONCLUSIONS
  Nowadays, the research on NPC transplantation in neurological disorders is advancing on two different fronts: on one hand, recent preclinical data are uncovering the molecular basis of NPC therapeutic plasticity, offering a more solid rational framework for the design of clinical studies. On the other hand, pilot trials are highlighting the safety and feasibility issues of neural stem cell transplantation that need to be addressed before efficacy could be properly evaluated.
authors.affiliation: Neuroimmunology Unit, Institute of Experimental Neurology (INSpe), Division of Neuroscience, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Donatella
authors.initials: D
authors.lastname: De Feo
authors.forename: Arianna
authors.initials: A
authors.lastname: Merlini
authors.forename: Cecilia
authors.initials: C
authors.lastname: Laterza
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
mesh_terms: D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000601:surgery*; D006801:Humans; D058953:Neural Stem Cells / Q000502:physiology* / Q000637:transplantation; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D033581:Stem Cell Transplantation / Q000379:methods*
chemical_list: D018696:Neuroprotective Agents