Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage

Beatriz Fernández-Muñoz, Cristina Rosell-Valle, Daniela Ferrari, Julia Alba-Amador, Miguel Ángel Montiel, Rafael Campos-Cuerva, Luis Lopez-Navas, María Muñoz-Escalona, María Martín-López, Daniela Celeste Profico, Manuel Francisco Blanco, Alessandra Giorgetti, Elena González-Muñoz, Javier Márquez-Rivas, Rosario Sanchez-Pernaute

Research output: Contribution to journalArticlepeer-review


Intraventricular 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.

Original languageEnglish
Pages (from-to)1085-1101
Number of pages17
JournalStem cells translational medicine
Issue number9
Publication statusPublished - Sep 1 2020


  • cerebrospinal fluid
  • germinal zone
  • intraventricular hemorrhage
  • neural stem cell
  • neurogenesis
  • premature infant

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology


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