Intracerebroventricular transplantation of human iPSC-derived neural stem cells (hiPSC-NSCs) into neonatal mice.

Abstract

Human neural stem cells (hNSCs) hold great promises for the development of cell-based therapies for neurodegenerative diseases, given their capability to provide immunomodulatory and trophic support and to replace, to a limited extent, damaged, or lost cells. Human NSCs are under clinical evaluation for the treatment of several neurodegenerative diseases. Still, issues related to the large-scale production of clinical-grade fetal hNSCs and their allogeneic nature-requiring immunosuppressive regimens-have hampered their full exploitation as therapeutics. NSCs derived from human induced pluripotent stem cells (hiPSCs) provide a valuable alternative to fetal hNSCs since they can be generated from autologous or HLA-matched donors expanded for large-scale clinical-grade production, and are amenable for gene addition/gene editing strategies, thus potentially addressing CNS diseases of genetic origin. The prospective use of hiPSC-derived NSCs (hiPSC-NSCs) for CNS-directed therapies demands a careful evaluation of the efficacy and safety of these cell populations in animal models. Here, we describe a protocol for the transplantation and phenotypical characterization of hiPSC-NSCs in neonatal immunodeficient mice. This protocol is relevant to assessing the safety and the efficacy of hiPSC-NSC transplantation to target early-onset neurodegenerative or demyelinating CNS diseases.

• Authors: Marco Luciani, Chiara Garsia, Elisabeth Mangiameli, Vasco Meneghini, Angela Gritti
• Journal: Methods in cell biology (Methods Cell Biol) Vol. 171 Pg. 127-147 ( 2022) ISSN: 0091-679X [Print] United States
• PMID: 35953197 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 Elsevier Inc. All rights reserved.

Topics

• Animals
• Animals, Newborn
• Cell Differentiation
• Gene Editing
• Humans
• Induced Pluripotent Stem Cells
• Mice
• Neural Stem Cells