Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a genetic motor neuron disease affecting infants. This condition is caused by mutations in the IGHMBP2 gene and currently has no cure. Stem cell transplantation is a potential therapeutic strategy for motor neuron diseases such as SMARD1, exerting beneficial effects both by replacing cells and by providing support to endogenous motor neurons. In this work, we demonstrate that human induced pluripotent stem cell (iPSC)-derived neural stem cells (NSCs) selected for the expression of specific markers, namely, Lewis X, CXCR4 and beta 1 integrin, and pretreated with neurotrophic factors and apoptosis/necroptosis inhibitors were able to effectively migrate and engraft into the host parenchyma after administration into the cerebrospinal fluid in a SMARD1 mouse model. We were able to detect donor cells in the ventral horn of the spinal cord and observe improvements in neuropathological features, particularly preservation of the integrity of the motor unit, that were correlated with amelioration of the SMARD1 disease phenotype in terms of neuromuscular function and lifespan. This minimally invasive stem cell approach can confer major advantages in the context of cell-mediated therapy for patients with neurodegenerative diseases.
CSF transplantation of a specific iPSC-derived neural stem cell subpopulation ameliorates the disease phenotype in a mouse model of spinal muscular atrophy with respiratory distress type 1 / G. Forotti, M. Nizzardo, M. Bucchia, A. Ramirez, E. Trombetta, S. Gatti, N. Bresolin, G.P. Comi, S. Corti. - In: EXPERIMENTAL NEUROLOGY. - ISSN 0014-4886. - 321(2019 Nov).
|Titolo:||CSF transplantation of a specific iPSC-derived neural stem cell subpopulation ameliorates the disease phenotype in a mouse model of spinal muscular atrophy with respiratory distress type 1|
NIZZARDO, MONICA (Secondo)
COMI, GIACOMO PIETRO (Penultimo)
CORTI, STEFANIA PAOLA (Ultimo) (Corresponding)
|Parole Chiave:||Neural stem cells; Spinal muscular atrophy with respiratory distress type 1; Transplantation|
|Settore Scientifico Disciplinare:||Settore MED/26 - Neurologia|
Settore BIO/05 - Zoologia
|Progetto:||Assessing the pathogenetic role of tRNA and rRNA deregulation in disease-specific human and mouse models to understand pathogenesis and identify molecular therapeutics targets for Spinal Muscular Atrophy with Respiratory Distress type 1|
Transferring autonomous and non autonomous cell degeneration 3D models between EU and USA for development of effective therapies for neurodegenerative diseases (ND) (CROSS-NEUROD)
|Data di pubblicazione:||nov-2019|
|Data ahead of print / Data di stampa:||21-ago-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.expneurol.2019.113041|
|Appare nelle tipologie:||01 - Articolo su periodico|