Remodelling the injured CNS through the establishment of atypical ectopic perivascular neural stem cell niches.
Compelling evidence exists that somatic neural stem/precursor cell (NPC)-based therapies protect the central nervous system (CNS) from chronic inflammation-driven degeneration, such as that occurring in experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), cerebral ischemic/hemorrhagic stroke and spinal cord injury (SCI). However, while it was first assumed that NPC transplants may act through direct replacement of lost/damaged cells, it has now become clear that they are able to protect the damaged nervous system through a number of 'bystander' mechanisms other than the expected cell replacement. In immune-mediated experimental demyelination--both in rodents and non-human primates--others and we have shown that transplanted NPC possess a constitutive and inducible ability to mediate efficient 'bystander' myelin repair and axonal rescue. This novel mechanism(s), which may improve the success of transplantation procedures, is likely to be exerted by undifferentiated NPCs whose functional characteristics are regulated by both CNS-resident and blood-borne inflammatory cells releasing in situ major stem cell regulators. Here, we discuss some of these alternative 'bystander' mechanisms, while pointing at the formation of the atypical ectopic perivascular niches, as the most challenging example of reciprocal biologically sound cross talk between the inflamed microenvironment(s) and transplanted therapeutic NPCs.
Pluchino
S
S
CNS Repair Unit, Institute of Experimental Neurology (INSPE), DIBIT2 and San Raffaele Scientific Institute, Milan, Italy. pluchino.stefano@hsr.it
Cusimano
M
M
Bacigaluppi
M
M
Martino
G
G
D000818:Animals; D002493:Central Nervous System Diseases / Q000276:immunology / Q000473:pathology / Q000601:surgery; D004195:Disease Models, Animal; D006801:Humans; D009474:Neurons / Q000502:physiology*; D055153:Stem Cell Niche / Q000166:cytology*; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000502:physiology*