Stroke is the leading cause of death and disability world-wide. Stroke patients often live with long-term motor and cognitive impairments. There is currently no effective treatment to reverse or significantly improve these neurological outcomes. The development of cellular reprogramming technology has the potential to provide novel cell-based strategies to treat stroke-related brain injury and dysfunction. Building on well described tenets of developmental biology, the landmark discovery of induced pluripotent stem cells using defined transcription factors has since been advanced to allow the direct reprogramming of one somatic cell type to another with the use of defined transcription factors to rapidly generate target cells to study cell biology or disease. Harnessing the potential of cellular reprogramming, either direct or through a pluripotent state, has enabled the study and promise of converting non-neuronal cells to neural cells. As such, the cellular reprogramming to replace neural cells lost following stroke injury and/or to convert “toxic” cells to pro-regenerative phenotypes, are potential avenues to promote neural repair and recovery of the stroke injured brain.
This Research Topic will explore avenues to bridge the gap between basic research and clinical application as it relates to identifying strategies that utilize cell reprogramming to replace lost cells in the stroke injured brain (such as neurons or oligodendrocytes for post-stroke grey and white matter repair, respectively). Moreover, it will shed light on the importance of targeting specific cell types for reprogramming (i.e. astrocytes within the glial scar; pro-inflammatory microglia, or pericytes). It will tackle questions about the types of cells that should be reprogrammed as well as the mechanisms that underly the reprogramming and the importance (if any) of generating specific neuronal phenotypes, in vivo. The in vivo aspect of the reprogramming field is critical now. Much has been learned about in vitro methodologies which provide insight into sources of neural cells for exogenous therapies (i.e. cell transplantation) but less is known about in vivo reprogramming in terms of the most appropriate cell type to target and how to generate specific cell types. There are many ways to implement cellular reprogramming through either genomic integration or integration-free methodologies. These include direct transduction of key transcription factors, mRNAs, recombinant proteins or micro-RNAs into non-neuronal cells to convert their cell identities into neurons or oligodendrocytes. Pharmacological and chemical reprogramming also receive great attention because of their easy access with spatially, temporally and dosing controllable and reversable features. This Research Topic aims to build on recent advances in understanding regulatory mechanisms and identifying strategies that can successfully reprogram non-neuronal cells for the purpose of clinical application to promote post-stroke tissue regeneration and functional recovery.
We welcome contributions in the form of Original Research, Brief Research Report, Review, Mini Review, and Methods that cover, but not limited to, the following sub-topics:
- Mechanistic insights in regulating nonneuronal cell (such as pericytes, astrocytes, fibroblasts) reprogramming into multipotent neural stem cells and/or directly into newly generated neurons or oligodendrocytes following stroke-related brain injury in vivo.
- Novel strategies in vitro that provide new sources of neural cells for the purpose of safe and efficacious transplantation post-stroke to regenerate damaged brain tissues.
- Application of in vivo cellular reprogramming methodologies through genetic integration or integration-free approaches in animal stroke models to promote brain regeneration and improve functional recovery.
- Modulation of niche environment by small molecules or chemical factors following stroke to enhance reprogramming nonneuronal cells into neural stem cells/neurons/oligodendrocytes for post-stroke regeneration and recovery.
Stroke is the leading cause of death and disability world-wide. Stroke patients often live with long-term motor and cognitive impairments. There is currently no effective treatment to reverse or significantly improve these neurological outcomes. The development of cellular reprogramming technology has the potential to provide novel cell-based strategies to treat stroke-related brain injury and dysfunction. Building on well described tenets of developmental biology, the landmark discovery of induced pluripotent stem cells using defined transcription factors has since been advanced to allow the direct reprogramming of one somatic cell type to another with the use of defined transcription factors to rapidly generate target cells to study cell biology or disease. Harnessing the potential of cellular reprogramming, either direct or through a pluripotent state, has enabled the study and promise of converting non-neuronal cells to neural cells. As such, the cellular reprogramming to replace neural cells lost following stroke injury and/or to convert “toxic” cells to pro-regenerative phenotypes, are potential avenues to promote neural repair and recovery of the stroke injured brain.
This Research Topic will explore avenues to bridge the gap between basic research and clinical application as it relates to identifying strategies that utilize cell reprogramming to replace lost cells in the stroke injured brain (such as neurons or oligodendrocytes for post-stroke grey and white matter repair, respectively). Moreover, it will shed light on the importance of targeting specific cell types for reprogramming (i.e. astrocytes within the glial scar; pro-inflammatory microglia, or pericytes). It will tackle questions about the types of cells that should be reprogrammed as well as the mechanisms that underly the reprogramming and the importance (if any) of generating specific neuronal phenotypes, in vivo. The in vivo aspect of the reprogramming field is critical now. Much has been learned about in vitro methodologies which provide insight into sources of neural cells for exogenous therapies (i.e. cell transplantation) but less is known about in vivo reprogramming in terms of the most appropriate cell type to target and how to generate specific cell types. There are many ways to implement cellular reprogramming through either genomic integration or integration-free methodologies. These include direct transduction of key transcription factors, mRNAs, recombinant proteins or micro-RNAs into non-neuronal cells to convert their cell identities into neurons or oligodendrocytes. Pharmacological and chemical reprogramming also receive great attention because of their easy access with spatially, temporally and dosing controllable and reversable features. This Research Topic aims to build on recent advances in understanding regulatory mechanisms and identifying strategies that can successfully reprogram non-neuronal cells for the purpose of clinical application to promote post-stroke tissue regeneration and functional recovery.
We welcome contributions in the form of Original Research, Brief Research Report, Review, Mini Review, and Methods that cover, but not limited to, the following sub-topics:
- Mechanistic insights in regulating nonneuronal cell (such as pericytes, astrocytes, fibroblasts) reprogramming into multipotent neural stem cells and/or directly into newly generated neurons or oligodendrocytes following stroke-related brain injury in vivo.
- Novel strategies in vitro that provide new sources of neural cells for the purpose of safe and efficacious transplantation post-stroke to regenerate damaged brain tissues.
- Application of in vivo cellular reprogramming methodologies through genetic integration or integration-free approaches in animal stroke models to promote brain regeneration and improve functional recovery.
- Modulation of niche environment by small molecules or chemical factors following stroke to enhance reprogramming nonneuronal cells into neural stem cells/neurons/oligodendrocytes for post-stroke regeneration and recovery.