Open AccessRabbit neurospheres as a novel in vitro tool for studying neurodevelopmental effects induced by intrauterine growth restriction
Author(s) -
Barenys Marta,
Illa Miriam,
Hofrichter Maxi,
Loreiro Carla,
Pla Laura,
Klose Jördis,
Kühne Britta Anna,
GómezCatalán Jesús,
Braun Jan Matthias,
Crispi Fatima,
Gratacós Eduard,
Fritsche Ellen
Publication year - 2021
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.20-0223
Subject(s) - neurosphere , neurogenesis , neural stem cell , progenitor cell , biology , progenitor , in vitro , oligodendrocyte , stem cell , immunology , endocrinology , neuroscience , microbiology and biotechnology , adult stem cell , endothelial stem cell , central nervous system , myelin , genetics
The aim of this study was to develop a rabbit neurosphere culture to characterize differences in basic processes of neurogenesis induced by intrauterine growth restriction (IUGR). A novel in vitro neurosphere culture has been established using fresh or frozen neural progenitor cells from newborn (PND0) rabbit brains. After surgical IUGR induction in pregnant rabbits and cesarean section 5 days later, neural progenitor cells from both control and IUGR groups were isolated and directly cultured or frozen at −80°C. These neural progenitor cells spontaneously formed neurospheres after 7 days in culture. The ability of control and IUGR neurospheres to migrate, proliferate, differentiate to neurons, astrocytes, or oligodendrocytes was compared and the possibility to modulate their responses was tested by exposure to several positive and negative controls. Neurospheres obtained from IUGR brains have a significant impairment in oligodendrocyte differentiation, whereas no significant differences are observed in other basic processes of neurogenesis. This impairment can be reverted by in vitro exposure of IUGR neurospheres to thyroid hormone, which is known to play an essential role in white matter maturation in vivo. Our new rabbit neurosphere model and the results of this study open the possibility to test several substances in vitro as neuroprotective candidates against IUGR induced neurodevelopmental damage while decreasing the number of animals and resources and allowing a more mechanistic approach at a cellular functional level.