Trophic and immunoregulatory properties of neural precursor cells: benefit for intracerebral transplantation.
Intracerebral xenotransplantation of porcine fetal neuroblasts (pNB) is considered as an alternative to human neuroblasts for the treatment of neurodegenerative diseases. However, pNB are systematically rejected, even in an immunoprivileged site such as the brain. Within this context, neural stem/precursor cells (NSPC), which were suggested as exhibiting low immunogenicity, appeared as a useful source of xenogeneic cells. To determine the advantage of using porcine NSPC (pNSPC) in xenotransplantation, pNB and pNSPC were grafted into the striatum of rats without immunosuppression. At day 63, all the pNB were rejected while 40% of the rats transplanted with pNSPC exhibited large and healthy grafts with numerous pNF70-positive cells. The absence of inflammation at day 63 and the occasional presence of T cells in pNSPC grafts evoked a weak host immune response which might be partly due to the immunosuppressive properties of the transplanted cells. T cell proliferation assays confirmed such a hypothesis by revealing an inhibitory effect of pNSPC on T cells through a soluble factor. In addition to their immunosuppressive effect, in contrast to pNB, very few pNSPC differentiated into tyrosine hydroxylase-positive neurons but the cells triggered an intense innervation of the striatum by rat dopaminergic fibers coming from the substantia nigra. Further experiments will be required to optimize the use of pNSPC in regenerative medicine but here we show that their immunomodulatory and trophic activities might be of great interest for restorative strategies. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."
Michel-Monigadon
Delphine
D
INSERM, UMR643, Nantes, France.
Bonnamain
Virginie
V
Nerrière-Daguin
Véronique
V
Dugast
Anne-Sophie
AS
Lévèque
Xavier
X
Plat
Martine
M
Venturi
Eric
E
Brachet
Philippe
P
Anegon
Ignacio
I
Vanhove
Bernard
B
Neveu
Isabelle
I
Naveilhan
Philippe
P
D000818:Animals; D049109:Cell Proliferation; D017690:Cell Transplantation / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005434:Flow Cytometry / Q000379:methods; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000196:embryology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000276:immunology* / Q000502:physiology*; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000601:surgery*; D016627:Oxidopamine / Q000633:toxicity; D051381:Rats; D011917:Rats, Inbred Lew; D013552:Swine; D013601:T-Lymphocytes / Q000502:physiology; D013997:Time Factors; D014183:Transplantation, Heterologous / Q000379:methods; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D016207:Cytokines; D009419:Nerve Tissue Proteins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase