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

Stem Cells Translational Medicine

Elena González‐Muñoz¹  Luis Lopez‐Navas²  Daniela Ferrari³  Javier Márquez‐Rivas⁴  Daniela Celeste Profico⁵  Rosario Sanchez‐Pernaute⁶  Alessandra Giorgetti⁷  María Martín‐López⁸  Cristina Rosell‐Valle⁸  Rafael Campos‐Cuerva⁸  Julia Alba‐Amador⁸  María Muñoz‐Escalona⁸  Manuel Francisco Blanco⁸  Beatriz Fernández‐Muñoz⁸  Miguel Ángel Montiel⁸ 

[1] Program for Translation of Regenerative Medicine in Catalonia (P‐CMRC) Barcelona Spain;Departamento de Preclínica Red Andaluza de Diseño y Traslación de Terapias Avanzadas Sevilla Spain;Department of Biotechnology and Biosciences University Milan‐Bicocca Milan Italy;Department of Cell Biology Genetics and Physiology, University of Málaga Málaga Spain;Fondazione IRCCS Casa Sollievo della Sofferenza Production Unit of Advanced Therapies (UPTA) San Giovanni Rotondo Italy;Grupo de Neurociencia aplicada Instituto de Biomedicina de Sevilla Sevilla Spain;Regenerative Medicine Program Bellvitge Biomedical Research Institute (IDIBELL);Unidad de Producción y Reprogramación Celular (UPRC) Red Andaluza para el diseño y traslación de Terapias Avanzadas Sevilla Spain;

关键词: cerebrospinal fluid;    germinal zone;    intraventricular hemorrhage;    neural stem cell;    neurogenesis;    premature infant;   

DOI  :  10.1002/sctm.19-0323

来源: DOAJ

【 摘 要 】

Abstract 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.

【 授权许可】

Unknown