Fernández-Muñoz, BeatrizRosell-Valle, CristinaFerrari, DanielaAlba-Amador, JuliaMontiel, Miguel ÁngelCampos-Cuerva, RafaelLopez-Navas, LuisMuñoz-Escalona, MaríaMartín-López, MaríaProfico, Daniela CelesteBlanco, Manuel FranciscoGiorgetti, AlessandraGonzález-Muñoz, ElenaMárquez-Rivas, JavierSanchez-Pernaute, Rosario2022-08-032022-08-032020Fernández-Muñoz B, Rosell-Valle C, Ferrari D, Alba-Amador J, Montiel MÁ, Campos-Cuerva R, et al. Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage. Stem Cells Transl Med. 2020 Sep;9(9):1085-11012157-6564http://hdl.handle.net/10668/3868Intraventricular hemorrhage is a common cause of morbidity and mortality in premature infants. The rupture of the germinal zone into the ventricles entails loss of neural stem cells and disturbs the normal cytoarchitecture of the region, compromising late neurogliogenesis. Here we demonstrate that neural stem cells can be easily and robustly isolated from the hemorrhagic cerebrospinal fluid obtained during therapeutic neuroendoscopic lavage in preterm infants with severe intraventricular hemorrhage. Our analyses demonstrate that these neural stem cells, although similar to human fetal cell lines, display distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain, the ganglionic eminences that give rise to interneurons and oligodendrocytes. These cells can be expanded, cryopreserved, and differentiated in vitro and in vivo in the brain of nude mice and show no sign of tumoral transformation 6 months after transplantation. This novel class of neural stem cells poses no ethical concerns, as the fluid is usually discarded, and could be useful for the development of an autologous therapy for preterm infants, aiming to restore late neurogliogenesis and attenuate neurocognitive deficits. Furthermore, these cells represent a valuable tool for the study of the final stages of human brain development and germinal zone biology.enAtribución 4.0 InternacionalAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Cerebrospinal fluidGerminal zoneIntraventricular hemorrhageNeural stem cellNeurogenesisPremature infantLíquido cefalorraquídeoCentro germinalHemorragia cerebral intraventricularCélulas madre nerviosasRecién nacido prematuroMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Diseases::Nervous System Diseases::Central Nervous System Diseases::Brain Diseases::Cerebrovascular Disorders::Intracranial Hemorrhages::Cerebral HemorrhageMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Techniques, Surgical::EndoscopyMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Gene Expression Regulation, DevelopmentalMedical Subject Headings::Persons::Persons::Age Groups::Infant::Infant, Newborn::Infant, PrematureMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice::Mice, Mutant Strains::Mice, NudeMedical Subject Headings::Anatomy::Cells::Stem Cells::Neural Stem CellsMedical Subject Headings::Anatomy::Fluids and Secretions::Body Fluids::Extracellular Fluid::Cerebrospinal Fluidresearch article32475061open access10.1002/sctm.19-03232157-6580PMC7445027