Abstract Details

Title Transplantation of iPSCs-Derived Neural Stem Cells as Therapeutic Approach for Amyotrophic Lateral Sclerosis

Topic Neural Repair/Rehabilitation

Presentation(s) S14 - (-)

Poster/Presentation
Number 006

Objective

Background Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease characterized by the loss of motor neurons. The possibility of reprogramming adult somatic cells into induced pluripotent stem cells (iPSCs) allows obtaining a promising cell source for modeling and cell therapy.

Design/Methods We generated iPS cell lines derived from human skin fibroblasts with a non-viral non integrating method based on the expression of reprogramming factors with episomal vectors. We differentiated iPSCs using a protocol to promote neuronal stem cells fate. We isolated by FACS a primitive NSC fraction based on their high ALDH activity and low side scatter (ADLHhiSSClo). The phenotype of these cells was analyzed by morphological, gene expression, and protein analysis. Finally, iPSC-purified NSCs were transplanted intrathecally or by systemic intravenous injection into ALS mice (SOD1G93A mice).

Results ALDH(hi)SSC(lo) NSCs from iPSCs are self-renewing and multipotent and can differentiate in vitro into the three neuroectodermal lineage in vitro. Both intrathecally and systemically grafted NSCs migrated into the parenchyma and engrafted the host spinal cord, expressing neuronal precursors- and neuronal mature-specific markers. Cell transplantation significantly prolonged disease duration and lifespan in SOD1G93A mice, promoted the survival of motor neurons and improved neuromuscular function.

Conclusions The major finding of the present study is that minimally invasive injection of ALDHhiSSClo cells in a mouse ALS model results in consistent engraftment of cells and is associated with an amelioration of the disease phenotype. These data suggest that iPSC derived NSCs represents a promising avenue for effective cell-based treatment for ALS and other neurodegenerative diseases.

Authors/Disclosures
Stefania Corti, MD, PhD (Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico) PRESENTER	Dr. Corti has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Corti has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Corti has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta.
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Nereo Bresolin, DR	No disclosure on file
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Hubert H. Fernandez, MD, FAAN (Center for Neurological Restoration, Cleveland Clinic)	Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amneal. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Intrance. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Fernandez has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Abbvie. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier. Dr. Fernandez has received publishing royalties from a publication relating to health care. Dr. Fernandez has received personal compensation in the range of $10,000-$49,999 for serving as a Steering Committee/Advisory Committee Member with Parkinson Study Group.

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