TY - JOUR
T1 - Neurospheres from neural stem/neural progenitor cells (NSPCs) of non-hydrocephalic HTx rats produce neurons, astrocytes and multiciliated ependyma
T2 - the cerebrospinal fluid of normal and hydrocephalic rats supports such a differentiation
AU - Henzi, Roberto
AU - Guerra, Montserrat
AU - Vío, Karin
AU - González, César
AU - Herrera, Cristian
AU - McAllister, Pat
AU - Johanson, Conrad
AU - Rodríguez, Esteban M.
N1 - Publisher Copyright:
© 2018, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Fetal onset hydrocephalus and abnormal neurogenesis are two inseparable phenomena turned on by a cell junction pathology first affecting neural stem/progenitor cells (NSPCs) and later the multiciliated ependyma. The neurological impairment of children born with hydrocephalus is not reverted by derivative surgery. NSPCs and neurosphere (NE) grafting into the cerebrospinal fluid (CSF) of hydrocephalic fetuses thus appears as a promising therapeutic procedure. There is little information about the cell lineages actually forming the NE as they grow throughout their days in vitro (DIV). Furthermore, there is no information on how good a host the CSF is for grafted NE. Here, we use the HTx rat, a model with hereditary hydrocephalus, with the mutation expressed in about 30% of the litter (hyHTx), while the littermates develop normally (nHTx). The investigation was designed (i) to establish the nature of the cells forming 4 and 6-DIV NE grown from NSPCs collected from PN1/nHTx rats and (ii) to study the effects on these NEs of CSF collected from nHTx and hyHTx. Immunofluorescence analyses showed that 90% of cells forming 4-DIV NEs were non-committed multipotential NSPCs, while in 6-DIV NE, 40% of the NSPCs were already committed into neuronal, glial and ependymal lineages. Six-DIV NE further cultured for 3 weeks in the presence of fetal bovine serum, CSF from nHTx or CSF from hyHTx, differentiated into neurons, astrocytes and βIV-tubulin+ multiciliated ependymal cells that were joined together by adherent junctions and displayed synchronized cilia beating. This supports the possibility that ependymal cells are born from subpopulations of NSC with their own time table of differentiation. As a whole, the findings indicate that the CSF is a supportive medium to host NE and that NE grafted into the CSF have the potential to produce neurons, glia and ependyma.
AB - Fetal onset hydrocephalus and abnormal neurogenesis are two inseparable phenomena turned on by a cell junction pathology first affecting neural stem/progenitor cells (NSPCs) and later the multiciliated ependyma. The neurological impairment of children born with hydrocephalus is not reverted by derivative surgery. NSPCs and neurosphere (NE) grafting into the cerebrospinal fluid (CSF) of hydrocephalic fetuses thus appears as a promising therapeutic procedure. There is little information about the cell lineages actually forming the NE as they grow throughout their days in vitro (DIV). Furthermore, there is no information on how good a host the CSF is for grafted NE. Here, we use the HTx rat, a model with hereditary hydrocephalus, with the mutation expressed in about 30% of the litter (hyHTx), while the littermates develop normally (nHTx). The investigation was designed (i) to establish the nature of the cells forming 4 and 6-DIV NE grown from NSPCs collected from PN1/nHTx rats and (ii) to study the effects on these NEs of CSF collected from nHTx and hyHTx. Immunofluorescence analyses showed that 90% of cells forming 4-DIV NEs were non-committed multipotential NSPCs, while in 6-DIV NE, 40% of the NSPCs were already committed into neuronal, glial and ependymal lineages. Six-DIV NE further cultured for 3 weeks in the presence of fetal bovine serum, CSF from nHTx or CSF from hyHTx, differentiated into neurons, astrocytes and βIV-tubulin+ multiciliated ependymal cells that were joined together by adherent junctions and displayed synchronized cilia beating. This supports the possibility that ependymal cells are born from subpopulations of NSC with their own time table of differentiation. As a whole, the findings indicate that the CSF is a supportive medium to host NE and that NE grafted into the CSF have the potential to produce neurons, glia and ependyma.
KW - Cerebrospinal fluid
KW - Congenital hydrocephalus
KW - Ependymogenesis
KW - Neural stem cells
KW - Neurospheres
UR - http://www.scopus.com/inward/record.url?scp=85045242585&partnerID=8YFLogxK
U2 - 10.1007/s00441-018-2828-8
DO - 10.1007/s00441-018-2828-8
M3 - Article
C2 - 29651556
AN - SCOPUS:85045242585
SN - 0302-766X
VL - 373
SP - 421
EP - 438
JO - Cell and Tissue Research
JF - Cell and Tissue Research
IS - 2
ER -