Neural Progenitors Derived From Human Induced Pluripotent Stem Cells Survive and Differentiate Upon Transplantation Into a Rat Model of Amyotrophic Lateral Sclerosis. (14th February 2013)

• Record Type: Journal Article
• Authors: Popescu, Iuliana Ristea; Nicaise, Charles; Liu, Song; Bisch, Grégoire; Knippenberg, Sarah; Daubie, Valery; Bohl, Delphine; Pochet, Roland
• Is Part Of: Stem cells translational medicine. Volume 2:Number 3(2013)
• Page Start: 167
• Page End: 174
• Publication Date: 2013-02-14
• Subjects: Spinal cord injury -- Stem cell transplantation -- Rat model -- Neurons -- Neural stem cell -- Neural differentiation; Stem cells -- Periodicals; Regenerative medicine -- Periodicals; Periodicals; 616.0277405
• DOI: 10.5966/sctm.2012-0042
• Languages: English
• ISSNs: 2157-6564

Abstract

Abstract : This study analyzed the fate of human induced pluripotent stem cell (iPSC)‐derived neural progenitors transplanted into the spinal cord of wild‐type and transgenic rats carrying a human mutated SOD1(G93A) gene. Results demonstrate proof‐of‐principle of survival and differentiation of human iPSC‐derived neural progenitors in in vivo amyotrophic lateral sclerosis (ALS) environment, offering perspectives for the use of iPSC‐based therapy in ALS. Abstract : Human induced pluripotent stem cells (iPSCs) offer hope for personalized regenerative cell therapy in amyotrophic lateral sclerosis (ALS). We analyzed the fate of human iPSC‐derived neural progenitors transplanted into the spinal cord of wild‐type and transgenic rats carrying a human mutated SOD1(G93A) gene. The aim was to follow survival and differentiation of human neural progenitors until day 60 post‐transplantation in two different in vivo environments, one being ALS‐like. iPSC‐derived neural progenitors efficiently engrafted in the adult spinal cord and survived at high numbers. Different neural progenitor, astroglial, and neuronal markers indicated that, over time, the transplanted nestin‐positive cells differentiated into cells displaying a neuronal phenotype in both wild‐type and transgenic SOD1 rats. Although a transient microglial phenotype was detected at day 15, astroglial staining was negative in engrafted cells from day 1 to day 60. At day 30, differentiation toward a neuronal phenotype was identified, which was further established at day 60 by the expression of the neuronal marker MAP2. A specification process into motoneuron‐like structures was evidenced in the ventral horns in both wild‐type and SOD1 rats. Our results demonstrate proof‐of‐principle of survival and differentiation of human iPSC‐derived neural progenitors in in vivo ALS environment, offering perspectives for the use of iPSC‐based therapy in ALS.