Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage.,STEM CELLS Translational Medicine

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Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage.
STEM CELLS Translational Medicine ( IF 5.4 ) Pub Date : 2020-05-30 , DOI: 10.1002/sctm.19-0323
Beatriz Fernández-Muñoz _{1,

2} , Cristina Rosell-Valle ₁ , Daniela Ferrari ₃ , Julia Alba-Amador ₁ , Miguel Ángel Montiel ₁ , Rafael Campos-Cuerva _{1,

4} , Luis Lopez-Navas ₅ , María Muñoz-Escalona ₁ , María Martín-López _{1,

2} , Daniela Celeste Profico ₆ , Manuel Francisco Blanco ₁ , Alessandra Giorgetti ₇ , Elena González-Muñoz _{8,

9,

10} , Javier Márquez-Rivas _{2,

11} , Rosario Sanchez-Pernaute ₅

Affiliation

Unidad de Producción y Reprogramación Celular (UPRC), Red Andaluza para el diseño y traslación de Terapias Avanzadas, Sevilla, Spain.
Grupo de Neurociencia aplicada, Instituto de Biomedicina de Sevilla, Sevilla, Spain.
Department of Biotechnology and Biosciences, University Milan-Bicocca, Milan, Italy.
Centro de Transfusiones, Tejidos y Células de Sevilla (CTTS), Sevilla, Spain.
Departamento de Preclínica, Red Andaluza de Diseño y Traslación de Terapias Avanzadas, Sevilla, Spain.
Fondazione IRCCS Casa Sollievo della Sofferenza, Production Unit of Advanced Therapies (UPTA), San Giovanni Rotondo, Italy.
Regenerative Medicine Program, Bellvitge Biomedical Research Institute (IDIBELL); Program for Translation of Regenerative Medicine in Catalonia (P-CMRC), Barcelona, Spain.
Department of Cell Biology, Genetics and Physiology, University of Málaga, Málaga, Spain.
Department of Regenerative Nanomedicine, Andalusian Center for Nanomedicine and Biotechnology-BIONAND, Málaga, Spain.
Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Carlos III Health Institute (ISCIII), Spain.
Neurosurgery Department, Hospital Virgen del Rocío, Sevilla, Spain.

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.

中文翻译：

从脑室内出血早产儿脑脊液中回收生发区神经干细胞。

脑室内出血是早产儿发病和死亡的常见原因。生发区破裂进入脑室会导致神经干细胞损失，并扰乱该区域的正常细胞结构，损害晚期神经胶质细胞生成。在这里，我们证明，可以从患有严重脑室内出血的早产儿的治疗性神经内窥镜灌洗期间获得的出血性脑脊液中轻松而可靠地分离出神经干细胞。我们的分析表明，这些神经干细胞虽然与人类胎儿细胞系相似，但显示出与其腹侧前脑生发区（产生中间神经元和少突胶质细胞的神经节隆起）的区域和发育起源相关的独特标志。这些细胞可以在裸鼠脑中体外和体内扩增、冷冻保存和分化，并且在移植后6个月没有显示出肿瘤转化的迹象。这种新型神经干细胞不会引起伦理问题，因为液体通常会被丢弃，并且可用于开发早产儿自体疗法，旨在恢复晚期神经胶质细胞生成并减轻神经认知缺陷。此外，这些细胞是研究人类大脑发育最后阶段和生发区生物学的宝贵工具。

更新日期：2020-05-30

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