Development of a therapeutic approach for Spinal Muscular Atrophy with Respiratory Distress (SMARD1) using human induced pluripotent stem cell-derived neural stem cells and motor neurons
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Data di Pubblicazione:
2013
Citazione:
Development of a therapeutic approach for Spinal Muscular Atrophy with Respiratory Distress (SMARD1) using human induced pluripotent stem cell-derived neural stem cells and motor neurons / S. C. Nizzardo M., F. Rizzo, M. Ruggieri, S. Salani, . Brajkovics, N. Bresolin, S. Corti. ((Intervento presentato al convegno Telethon tenutosi a Riva del Garda nel 2013.
Abstract:
Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a fatal form of infantile motor neuron disease caused by mutations in the IGHMBP2 gene. Currently, there is no cure. We previously described that transplantation of motor neurons derived from murine pluripotent stem cells can ameliorate the disease phenotype in a SMARD1 mouse model.
In this project, we investigated the therapeutic potential of transplantation of human neural stem cells and motor neurons derived from induced pluripotent stem cells (iPSCs) as therapeutic strategy for SMARD1. We generated iPSCs from human healthy fibroblasts, using a non viral method based on non integrating episomal vectors. These cells were differentiated into neural stem cells and motor neurons and characterized by morphological, gene expression, and protein analysis. iPSC-purified motor neurons were transplanted into the spinal cords of SMARD1 mice. We determined the survival, differentiation, and function of motor neurons after engraftment. We identified human-derived motoneurons, which presented motoneuronal phenotype and coexpressed HB9 and ChAT, within the ventral horns of all transplanted animals. We demonstrated also that transplanted cells improve the phenotype of treated animals in their neuromuscular function and survival. Our goal is to examine bi-directional cellular and molecular interactions between transplanted donor-derived motor neurons and host cells to elucidate the mechanisms that underlie the amelioration of disease phenotype other than cell replacement. This study demonstrated that transplantation of iPS derived motoneurons is feasible in an animal model of a human motoneuron disease, contributing in the development of a therapy for SMARD1 and other motor neuron disorders.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Elenco autori:
S. C. Nizzardo M., F. Rizzo, M. Ruggieri, S. Salani, . Brajkovics, N. Bresolin, S. Corti
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