Publication: Limitations and challenges of direct cell reprogramming in vitro and in vivo
Authors
Zhang, Yi-Xuan ; Chen, Si-Lin ; Li, Yu-Mei ; Zheng, Yun-Wen
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Publisher
Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-458
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info:eu-repo/semantics/article
Description
Abstract
Direct reprogramming, whether in vitro or in
vivo, has attracted great attention because of its
advantages of convenience, short-term conversion, direct
targets, no immune rejection, and potential clinical
applications. In addition, due to its independence from
the pluripotent state, direct programming minimizes
some safety concerns associated with the use of human
pluripotent stem cells. However, the significant
limitations of reprogrammed cells, such as poor
proliferative ability, low efficiency, and immature
function, need to be addressed before the clinical
application potential can be expanded. Here, we review
the recent achievements of direct reprogramming in 2D
and 3D systems in vitro and in vivo, covering cells
derived from the three germ layers from stem/progenitor
cells to terminal cells, such as hepatocytes, pancreatic β
cells, cardiomyocytes, endothelial cells, osteoblasts,
chondrocytes, neurons, and melanocytes. Combining our
lab experiences with current work, we summarize the
practical and potential issues that need to be solved and
the prospects of strategies for addressing the current
dilemmas. Through comprehensive analyses, it is
concluded that the directions for dealing with efficiency
and functionality issues could be the optimization of
transcription factors, the upgradation for delivery
systems, the regulation of epigenetic factors and
pathways, and the improvement of cellular maintenance
conditions. Besides, converting cells into the progenitor
state firstly and then differentiating them into the desired
cell types with chemical compounds may provide an
approach to obtaining functional and safe converted cells
in batches with a better proliferative ability. With the
emergence of more and more direct reprogramming
techniques and approaches with both safety and
effectiveness, it is bound to bring a new dawn for
mechanism research and therapeutic applications for
relevant diseases in the future.
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Citation
Histology and Histopathology Vol. 37, nº8 (2022)
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