Potentials of Cellular Reprogramming as a Novel Strategy for Neuroregeneration

Abstract

Cellular reprogramming technology holds great potential for tissue repair and regeneration to replace cells that are lost due to diseases or injuries. In addition to the landmark discovery of induced pluripotent stem cells, advances in cellular reprogramming allow the direct lineage conversion of one somatic cell type to another using defined transcription factors. This direct reprogramming technology represents a rapid way to generate target cells in the laboratory, which can be used for transplantation and studies of biology and diseases. More importantly, recent work has demonstrated the exciting application of direct reprogramming to stimulate regeneration in vivo, providing an alternative approach to transplantation of donor cells. Here, we provide an overview of the underlying concept of using cellular reprogramming to convert cell fates and discuss the current advances in cellular reprogramming both in vitro and in vivo, with particular focuses on the neural and retinal systems. We also discuss the potential of in vivo reprogramming in regenerative medicine, the challenges and potential solutions to translate this technology to the clinic.

Dual modulation of neuron‐specific microRNAs and the REST complex promotes functional maturation of human adult induced neurons

“…Induced neurons can be used for disease modeling, diagnostics, and drug screening [2,30,31]. As the technology becomes more and more refined, the use of iNs to model neurological diseases is increasing.…”

Hypoxia in Cell Reprogramming and the Epigenetic Regulations

“…These conditional ischemic events via low oxygen stimulation are an intriguing prospect for future investigation. They suggest that a low oxygen environment may contribute or regulate the processes of tissue regeneration (Fang et al, 2018 ; Huels and Medema, 2018 ; Yui et al, 2018 ). There is undeniable involvement of HIF signaling and epigenetics during events that determine cell fate and cause rapid proliferation and differentiation.…”

Direct Reprogramming of Human Fetal- and Stem Cell-Derived Glial Progenitor Cells into Midbrain Dopaminergic Neurons

“…So far, a number of somatic cell types, including fibroblasts, hepatocytes, pericytes, and glia, have been successfully converted to neurons ( Masserdotti et al., 2016 ). Since the direct conversion strategy does not rely on a proliferative intermediate, some of the safety concerns associated with the use of human pluripotent stem cells (hPSCs) are minimized, and both autologous and allogeneic strategies could be used ( Fang et al., 2018 ; Grealish et al., 2016 ). As an extension of direct conversion in cell-based therapies, delivery of the conversion factors directly to the brain with the aim of converting endogenous glia is being developed as an alternative approach for the generation of therapeutic neurons in situ ( Vignoles et al., 2019 ) .…”