In Vivo Direct Reprogramming of Reactive Glial Cells into Functional Neurons after Brain Injury and in an Alzheimer’s Disease Model
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This chapter contains sections titled: Introduction Reprogramming during Fertilization Reprogramming during Somatic Cell Nuclear Transfer (SCNT) Reprogramming with Cell Extracts Reprogramming with Transcription Factors: Induced Pluripotent Stem (iPS) Cells Conclusion References
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Pluripotent stem cells (PSCs) derived from somatic cells represent a powerful experimental tool for investigating the molecular mechanisms underlying the disease phenotype; with prospects to advance medical therapies. They also have significant potential as a renewable source of autologous cells for cellular therapy. Various approaches for PSC derivation from somatic cells have been reported in the literature. The method used for reprogramming is particularly relevant as it may affect the characteristics and quality of PSCs. This review will present an overview of the basic strategies and methods for reprogramming to pluripotency. These strategies will be briefly discussed in the context of how the mechanism of reprogramming could influence PSC characteristics with respect to safety and quality. Aspects of the reprogramming approach that can influence PSC properties, such as culture conditions and donor cell source, are also discussed. Keywords: iPSCs, nuclear reprogramming, pluripotent stem cells, reprogramming, reprogramming strategies, reprogramming technology.
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Induced pluripotent stem cells (iPSCs) can be generated from somatic cells by ectopically expressing a set of reprogramming factors. iPSCs hold tremendous promise for cell replacement therapy, drug discovery, and disease modeling. However, the efficiency of iPSC generation is extremely low and the quality of derived iPSCs is often poor. Many small molecules that are able to improve reprogramming by either modifying epigenetic barriers or targeting signaling pathways have recently been identified. Chemical compounds are a unique tool that can not only facilitate reprogramming but perhaps also improve our understanding of the reprogramming mechanism that allows us to generate safe iPSCs for therapeutic use.
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Functional reprogramming of a differentiated cell toward pluripotent cell may have long-term applications in numerous aspects, especially in regenerative medicine. Evidences accumulating from recent studies suggest that cellular extracts from stem cells or pluripotent cells can induce epigenetic reprogramming and facilitate pluripotency in otherwise highly differentiated cell types. Epigenetic reprogramming using cellular extracts has gained increasing attention and applied to recognize the functional factors, acquire the target cell types, and explain the mechanism of reprogramming. Now, more and more researches have proved that cellular extract treatment is an important strategy of cellular reprogramming. Thus, this review mainly focused on the progresses and potential mechanisms in epigenetic reprogramming using cellular extracts.
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Direct reprogramming of somatic cells into a pluripotent state has been achieved with a set of just four transcription factors. Many scientists and medical doctors are trying to elucidate the causes of intractable diseases and discover new drugs using the newest types of technology. Various methods have been developed to produce clinical‐grade fully reprogrammed cells for cell transplantation therapy. Augmenting agents, such as small‐molecules, have been extensively screened to improve the reprogramming efficiency. The molecular mechanisms of reprogramming have been revealed by embryonic stem cell research. The accumulation of knowledge by the pioneers has driven the reprogramming field. In the present article, the contents of gift boxes from the studies of pluripotency to the nuclear reprogramming field are introduced.
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The slow and inefficient of reprogramming of somatic cells in mammals imposes limitations to mechanistic studies and potential clinical translation.The reprogramming progress involves the changes of cellular genes expression,understanding and controlling epigenetic modification is the key to successful reprogramming.Here,we reviewed progresses on epigenetic influences on gene expression,epigenetic control in dedifferentiation and transdifferentiation,the usage of chemical inhibitors and signaling molecules that could either enhance reprogramming efficiency or replace core reprogramming factors in order to benefit the elucidation of reprogramming of somatic cells and provide reference for the formation of pluripotent stem cells induced from differentiated somatic cells with only chemicals.
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Objectives: In the fields of tissue engineering, regenerative medicine, and disease modeling the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) is gaining in importance. The footprint-free generated patient-specific iPSCs have a tremendous potential as a cell source for the creation of desired types of autologous cells. In this study, the reprogramming of human fibroblasts using synthetic modified messenger RNAs (mRNAs) or self-replicating RNAs (srRNAs) encoding the reprogramming factors was compared.
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