FM19G11-Loaded Gold Nanoparticles Enhance the Proliferation and Self-Renewal of Ependymal Stem Progenitor Cells Derived from ALS Mice

• Published in: Cells (Basel, Switzerland) Vol. 8; no. 3; p. 279
• Main Authors: Marcuzzo, Stefania, Isaia, Davide, Bonanno, Silvia, Malacarne, Claudia, Cavalcante, Paola, Zacheo, Antonella, Laquintana, Valentino, Denora, Nunzio, Sanavio, Barbara, Salvati, Elisa, Andreozzi, Patrizia, Stellacci, Francesco, Krol, Silke, Mellado-López, Maravillas, Mantegazza, Renato, Moreno-Manzano, Victoria, Bernasconi, Pia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.03.2019; MDPI
• Subjects: AKT1 protein; Amyotrophic Lateral Sclerosis; Animals; Benzamides - pharmacology; Biomarkers - metabolism; Cell cycle; Cell Cycle - drug effects; Cell proliferation; Cell Proliferation - drug effects; Cell Self Renewal - drug effects; Cell self-renewal; Cellular Biology; Ependyma - cytology; ependymal stem progenitor cells; FM19G11; G93A-SOD1 mouse model; Gene expression; Gene Expression Regulation - drug effects; Gold - chemistry; Humans; Hypoxia; Hypoxia-inducible factors; Kinases; Life Sciences; Ligands; Metal Nanoparticles - chemistry; Mice, Transgenic; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Mitochondria; Motor neurons; Nanoparticles; Neurodegeneration; Neurodegenerative diseases; Oct-4 protein; Octamer Transcription Factor-3 - metabolism; Pluripotency; Pluripotent Stem Cells - metabolism; Progenitor cells; Proteins; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; PTEN protein; SOXB1 Transcription Factors - metabolism; Spinal cord; Spinal cord injuries; Stem cells; Stem Cells - cytology; Stem Cells - drug effects; Superoxide dismutase; Superoxide Dismutase-1 - metabolism; Transcription; Uncoupling Protein 2 - metabolism; United States > US; nanoparticles; amyotrophic lateral sclerosis; FM19G11; G93A-SOD1 mouse model; ependymal stem progenitor cells
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells8030279

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons. In ALS mice, neurodegeneration is associated with the proliferative restorative attempts of ependymal stem progenitor cells (epSPCs) that normally lie in a quiescent in the spinal cord. Thus, modulation of the proliferation of epSPCs may represent a potential strategy to counteract neurodegeneration. Recent studies demonstrated that FM19G11, a hypoxia-inducible factor modulator, induces epSPC self-renewal and proliferation. The aim of the study was to investigate whether FM19G11-loaded gold nanoparticles (NPs) can affect self-renewal and proliferation processes in epSPCs isolated from G93A-SOD1 mice at disease onset. We discovered elevated levels of SOX2, OCT4, AKT1, and AKT3, key genes associated with pluripotency, self-renewal, and proliferation, in G93A-SOD1 epSPCs at the transcriptional and protein levels after treatment with FM19G11-loaded NPs. We also observed an increase in the levels of the mitochondrial uncoupling protein (UCP) gene in treated cells. FM19G11-loaded NPs treatment also affected the expression of the cell cycle-related microRNA (miR)-19a, along with its target gene PTEN, in G93A-SOD1 epSPCs. Overall our findings establish the significant impact of FM19G11-loaded NPs on the cellular pathways involved in self-renewal and proliferation in G93A-SOD1 epSPCs, thus providing an impetus to the design of novel tailored approaches to delay ALS disease progression.