Dataset Information

Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment.

ABSTRACT: Stroke is the main cause of disability and death in the world within neurological diseases. Despite such a huge impact, enzymatic, and mechanical recanalization are the only treatments available so far for ischemic stroke, but only <20% of patients can benefit from them. The use of stem cells as a possible cell therapy in stroke has been tested for years. The results obtained from these studies, although conflicting or controversial in some aspects, are promising. In the last few years, the recent development of the induced pluripotent stem cells has opened new possibilities to find new cell therapies against stroke. In this review, we will provide an overview of the state of the art of cell therapy in stroke. We will describe the current situation of the most employed stem cells and the use of induced pluripotent stem cells in stroke pathology. We will also present a summary of the different clinical trials that are being carried out or that already have results on the use of stem cells as a potential therapeutic intervention for stroke.

SUBMITTER: Fernandez-Susavila H

PROVIDER: S-EPMC6722184 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment.

Fernández-Susavila Héctor H Bugallo-Casal Ana A Castillo José J Campos Francisco F

Frontiers in neurology 20190828

Stroke is the main cause of disability and death in the world within neurological diseases. Despite such a huge impact, enzymatic, and mechanical recanalization are the only treatments available so far for ischemic stroke, but only <20% of patients can benefit from them. The use of stem cells as a possible cell therapy in stroke has been tested for years. The results obtained from these studies, although conflicting or controversial in some aspects, are promising. In the last few years, the rece ...[more]

PMID: 31555195

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Project description:UnlabelledComprehensive analyses comparing individual DNA damage response (DDR) of induced pluripotent stem cells (iPSCs) with neonatal stromal cells with respect to their developmental age are limited. The imperative necessity of providing developmental age-matched cell sources for meaningful toxicological drug safety assessments in replacement of animal-based testing strategies is evident. Here, DDR after radiation or treatment with N-methyl-N-nitrosurea (MNU) was determined in iPSCs compared with neonatal and bone marrow stromal cells. Neonatal and adult stromal cells showed no significant morphologically detectable cytotoxicity following treatment with 1 Gy or 1 mM MNU, whereas iPSCs revealed a much higher sensitivity. Foci analyses revealed an effective DNA repair in stromal cell types and iPSCs, as reflected by a rapid formation and disappearance of phosphorylated ATM and γH2AX foci. Furthermore, quantitative polymerase chain reaction analyses revealed the highest basic expression level of DDR and repair-associated genes in iPSCs, followed by neonatal stromal cells and adult stromal cells with the lowest expression levels. In addition, the influence of genotoxic stress prior to and during osteogenic differentiation of neonatal and adult stromal cells was analyzed applying common differentiation procedures. Experiments presented here suggest a developmental age-dependent basic expression level of genes involved in the processing of DNA damage. In addition a differentiation-dependent downregulation of repair genes was observed during osteogenesis. These results strongly support the requirement to provide adequate cell sources for toxicological in vitro drug testing strategies that match to the developmental age and differentiation status of the presumptive target cell of interest.SignificanceThe results obtained in this study advance the understanding of DNA damage processing in human neonatal stromal cells as compared with adult stromal cells and induced pluripotent stem cells (iPSCs). The data suggest developmental age-dependent differences in DNA damage repair capacity. In iPSCs (closest to embryonic stem cells), the highest expression level of DNA damage response and repair genes was found, followed by neonatal stromal cells and adult stromal cells with the lowest overall expression. In addition, a differentiation-dependent downregulation of repair capacity was observed during osteogenic differentiation in neonatal stromal cells. Notably, the impact of genotoxic stress on osteogenic differentiation depended on the time the genotoxic insult took place and, moreover, was agent-specific. These results strongly support the necessity of offering and establishing adequate cell sources for informative toxicological testing matching to the developmental age and differentiation status of the respective cell of interest.

Dataset Information

Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment.

Publications

Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment.

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