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Review
, 2018, 5630802
eCollection

Molecular Mechanisms of Transdifferentiation of Adipose-Derived Stem Cells Into Neural Cells: Current Status and Perspectives

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Review

Molecular Mechanisms of Transdifferentiation of Adipose-Derived Stem Cells Into Neural Cells: Current Status and Perspectives

Liang Luo et al. Stem Cells Int.

Abstract

Neurological diseases can severely compromise both physical and psychological health. Recently, adult mesenchymal stem cell- (MSC-) based cell transplantation has become a potential therapeutic strategy. However, most studies related to the transdifferentiation of MSCs into neural cells have had disappointing outcomes. Better understanding of the mechanisms underlying MSC transdifferentiation is necessary to make adult stem cells more applicable to treating neurological diseases. Several studies have focused on adipose-derived stromal/stem cell (ADSC) transdifferentiation. The purpose of this review is to outline the molecular characterization of ADSCs, to describe the methods for inducing ADSC transdifferentiation, and to examine factors influencing transdifferentiation, including transcription factors, epigenetics, and signaling pathways. Exploring and understanding the mechanisms are a precondition for developing and applying novel cell therapies.

Figures

Figure 1
Figure 1
A schematic for the transdifferentiation of ADSCs into NSCs and neural cells, indicating relevant influences such as cell surface markers, transcriptional factors, culture media, and signaling pathways. The details can be seen in the text. TFs: transcription factors; miRs: microRNAs; GFs: growth factors; MSCs: mesenchymal stem cells; PSA-NCAM: polysialic acid neural cell adhesion molecule; GlcNAc: N-acetylglucosamine; PDGF: platelet-derived growth factor; IGF: insulin-like growth factor; CNTF: ciliary neurotrophic factor; GABA: γ-aminobutyric acid; GDNF: glial-derived neurotrophic factor; BDNF: brain-derived neurotrophic factor; T3: 3,5,3′-triiodothyronine; NT3: neurotrophin-3.
Figure 2
Figure 2
Overview of several important pathways involved in regulating the transdifferentiation of NSCs and neural cells. The Wnt, Notch, hedgehog, and TGF-β signaling pathways have been implicated in the transdifferentiation of neural cells. Activation or inhibition of these signaling pathways as well as their cross-talk may initiate cell conversion, maintain the self-renewal of stem cells, and drive their transdifferentiation. Akt: protein kinase B; Dvl: dishevelled; GFs: growth factors; GliR: Gli repressors; GSK3β: glycogen synthase 3 beta; LEF1: lymphoid-enhancing factor-1; NICD1: Notch intracellular domain-1; PI3K: phosphatidylinositol-3-kinase; PKA: protein kinase A; Ptch: patched; R-smad: receptor-regulated Smads; Shh: sonic hedgehog protein; SMO: smoothened; TCF: T cell factor transcription factor; Wnt: wingless.

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