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NSCs Isolated from Preterm Infants May Pave the Way to New Treatment Strategies

Review of "Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage" from STEM CELLS Translational Medicine by Stuart P. Atkinson

Intraventricular hemorrhage (IVH), a common complication of premature infants with low birth weight [1], initiates in a highly proliferative and highly vascularized region around the lateral ventricles known as the periventricular germinal zone [2]. The vasculature weakness and blood pressure fluctuations associated with premature birth [2] may contribute to germinal zone bleeding, which can develop into a hemorrhagic phase associated with the loss of neural stem cells (NSCs), cytoarchitectural and neurogliogenic compromise [3], and morbidity and mortality. 

Clinical‐grade human allogenic fetal NSCs have been proven safe following their clinical evaluation for various neurological disorders [4], although their efficacy has yet to be fully established. Now, researchers led by Beatriz Fernández‐Muñoz (Unidad de Producción y Reprogramación Celular, Sevilla, Spain) have reported the isolation and characterization of NSCs from the hemorrhagic cerebrospinal fluid of preterm infants in a new STEM CELLS Translational Medicine study [5] in the hope of employing them as part of therapeutic approaches aiming to restore neurogliogenesis and attenuate neurocognitive deficits.

The authors readily isolated NSCs from the hemorrhagic cerebrospinal fluid using therapeutic neuroendoscopic lavage, a minimally invasive technique used to remove hemorrhagic cerebrospinal fluid to mitigate potential adverse effects in preterm infants with severe intraventricular hemorrhage. Of note, this fluid from this procedure is typically discarded and so represents an ethical means of deriving NSCs that may find use in autologous therapies for preterm infants.

Further evaluations established that isolated NSCs could be readily expanded, cryopreserved, and differentiated in vitro and in vivo following transplantation into the brains of nude mice; furthermore, these NSCs failed to display signs of pro-tumorigenic capacity up to six months after their transplantation. The analysis of recovered NSCs also suggested broad similarities to human fetal NSC lines; however, they also exhibited distinctive hallmarks related to their regional and developmental origin in the germinal zone of the ventral forebrain.

While these NSCs can be applied in the development of autologous cell therapies that aim to reduce neurological disability in preterm infants, and thereby act as an alternative to mesenchymal stem cells (as described in these recent STEM CELLS Translational Medicine articles [6, 7]), they may also represent a valuable tool regarding the study of the final stages of human brain development and germinal zone biology.

For more on the potential of these novel NSCs, stay tuned to the Stem Cells Portal!



  1. Khanafer-Larocque I, Soraisham A, Stritzke A, et al., Intraventricular Hemorrhage: Risk Factors and Association With Patent Ductus Arteriosus Treatment in Extremely Preterm Neonates. Frontiers in Pediatrics 2019;7:408.
  2. Inder TE, Perlman JM, and Volpe JJ, Chapter 24 - Preterm Intraventricular Hemorrhage/Posthemorrhagic Hydrocephalus, in Volpe's Neurology of the Newborn (Sixth Edition), J.J. Volpe, et al., Editors. 2018, Elsevier. p. 637-698.e21.
  3. McAllister JP, Guerra MM, Ruiz LC, et al., Ventricular Zone Disruption in Human Neonates With Intraventricular Hemorrhage. Journal of Neuropathology & Experimental Neurology 2017;76:358-375.
  4. Tang Y, Yu P, and Cheng L, Current progress in the derivation and therapeutic application of neural stem cells. Cell Death & Disease 2017;8:e3108-e3108.
  5. Fernández-Muñoz B, Rosell-Valle C, Ferrari D, et al., Retrieval of germinal zone neural stem cells from the cerebrospinal fluid of premature infants with intraventricular hemorrhage. STEM CELLS Translational Medicine 2020;9:1085-1101.
  6. Ahn SY, Chang YS, Sung SI, et al., Mesenchymal Stem Cells for Severe Intraventricular Hemorrhage in Preterm Infants: Phase I Dose-Escalation Clinical Trial. STEM CELLS Translational Medicine 2018;7:847-856.
  7. Vinukonda G, Liao Y, Hu F, et al., Human Cord Blood-Derived Unrestricted Somatic Stem Cell Infusion Improves Neurobehavioral Outcome in a Rabbit Model of Intraventricular Hemorrhage. STEM CELLS Translational Medicine 2019;8:1157-1169.