Abstract

Recent studies have revealed that a combination of chemical compounds enables direct reprogramming from one somatic cell type into another without the use of transgenes by regulating cellular signaling pathways and epigenetic modifications. The generation of induced pluripotent stem (iPS) cells generally requires virus vector-mediated expression of multiple transcription factors, which might disrupt genomic integrity and proper cell functions. The direct reprogramming is a promising alternative to rapidly prepare different cell types by bypassing the pluripotent state. Because the strategy also depends on forced expression of exogenous lineage-specific transcription factors, the direct reprogramming in a chemical compound-based manner is an ideal approach to further reduce the risk for tumorigenesis. So far, a number of reported research efforts have revealed that combinations of chemical compounds and cell-type specific medium transdifferentiate somatic cells into desired cell types including neuronal cells, glial cells, neural stem cells, brown adipocytes, cardiomyocytes, somatic progenitor cells, and pluripotent stem cells. These desired cells rapidly converted from patient-derived autologous fibroblasts can be applied for their own transplantation therapy to avoid immune rejection. However, complete chemical compound-induced conversions remain challenging particularly in adult human-derived fibroblasts compared with mouse embryonic fibroblasts (MEFs). This review summarizes up-to-date progress in each specific cell type and discusses prospects for future clinical application toward cell transplantation therapy.

Highlights

  • Differentiated cells acquire a pluripotent state by forced expression of Yamanaka’s reprogramming factors [1,2,3]

  • We recently reported that human dermal fibroblasts were converted into chemical compound-induced brown adipocytes [53]

  • Ieda et al [10] first reported that cardiac fibroblasts that constituted over 50% of the cells in the heart were directly converted into cardiomyocyte-like cells by forced expression of a set of cardiac transcription factors, Gata4, Mef2c, and Tbx5

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Summary

Review Article

Because the strategy depends on forced expression of exogenous lineage-specific transcription factors, the direct reprogramming in a chemical compound-based manner is an ideal approach to further reduce the risk for tumorigenesis. A number of reported research efforts have revealed that combinations of chemical compounds and cell-type specific medium transdifferentiate somatic cells into desired cell types including neuronal cells, glial cells, neural stem cells, brown adipocytes, cardiomyocytes, somatic progenitor cells, and pluripotent stem cells. These desired cells rapidly converted from patient-derived autologous fibroblasts can be applied for their own transplantation therapy to avoid immune rejection.

Introduction
Neuronal cells
Human dermal
Human primary astrocytes
Human primary
Neural stem cells
Fetal adult
Primary murine astrocytes bFGF
Brown adipocytes
Brown adipocyte
Tauroursodeoxycholic acid
Hepatocytes and pancreatic β cells
Endoderm progenitor cells and somatic stem cells
Endoderm progenitor cells hGECs
Human dermal fibroblasts
Pluripotent stem cells
Induced pluripotent stem cells
Mouse small intestinal epithelial cells
Chemical compounds for direct reprogramming
Findings
Conclusion
Full Text
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