Wnt signaling activation: targets and therapeutic opportunities for stem cell therapy and regenerative medicine

Bonnet, Clémence; Brahmbhatt, Anvi; Deng, Sophie X.; Zheng, Jie

doi:10.1039/d1cb00063b

Cited by 19 publications

(13 citation statements)

References 206 publications

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“…Our findings are in line with previously reported studies that demonstrate the activation of Wnt signaling during cell proliferation and inhibition when the cells initiate differentiation and lineage commitment. [30][31][32] A previous study also showed that the suppression of Wnt signaling in medial ganglionic eminence cells facilitate these proliferative cells to exit cell cycle to induce neuronal differentiation, whereas its activation retains the proliferative state with sustained differentiation potential via activation of Notch signaling. 33…”

Section: Discussionmentioning

confidence: 99%

Alpha terpineol directs bone marrow mesenchymal stem cells toward neuronal lineage through regulation of wnt signaling pathway

Ishaque

Salim

Simjee

et al. 2023

Cell Biochemistry & Function

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Central nervous system anomalies give rise to neuropathological consequences with immense damage to the neuronal tissues. Cell based therapeutics have the potential to manage several neuropathologies whereby the differentiated cells are explored for neuronal regeneration. The current study analyzes the effect of a bioactive compound, alpha terpineol (AT) on the differentiation of rat bone marrow derived mesenchymal stem cells (BM-MSCs) toward neuronal lineage, and explores regulation of differentiation process through the study of Wnt pathway mediators. BM-MSCs were cultured and characterized based on their surface markers and trilineage differentiation. Safe dose of AT as optimized by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide assay, was used for the treatment of MSCs. Treated cells were analyzed for the neuronal, astroglial and germ layer transition markers at the gene and protein levels, by quantitative polymerase chain reaction and immunocytochemistry, respectively. Temporal expression of Wnt pathway genes was assessed during the course of neuronal differentiation. AT treated group showed significant upregulation of neuron specific (NSE, MAP2, Tau, Nestin, and NefL) and astroglial (GFAP) genes with positive expression of late neuronal markers. Germ layer transition analysis showed the overexpression of ectodermal markers (NCAM, Nestin, and Pax6), whereas endodermal (AFP, MixL1, and Sox17),and mesodermal (Mesp1 and T Brachyury) markers were also found to be upregulated. Wnt signaling pathway was activated during the initial phase (30 min) of differentiation, which later was downregulated at 1, 3, and 5 h. AT efficiently induces neuronal differentiation of BM-MSCs by regulating Wnt signaling. Overexpression of both early and late neuronal markers indicate their neuro-progenitor state and thus can be utilized as a promising approach in cellular therapeutics to treat various neurodegenerative ailments. In addition, exploration of the molecular pathways may be helpful to understand the mechanism of cell-based neuronal regeneration.

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Section: Discussionmentioning

confidence: 99%

Alpha terpineol directs bone marrow mesenchymal stem cells toward neuronal lineage through regulation of wnt signaling pathway

Ishaque

Salim

Simjee

et al. 2023

Cell Biochemistry & Function

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“…Previous studies also suggested that the up-regulation of glycolysis can be an effective strategy for anagen induction and hair growth promotion [14,15]. In addition, activation of stem cells using small molecules inducing the Wnt/β-catenin signaling pathway was suggested as a strategy for hair re-growth and regeneration [23,44]. Therefore, small molecular control of HFSC metabolism is a promising strategy for hair regeneration.…”

Section: Discussionmentioning

confidence: 99%

Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling

et al. 2022

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Hair follicle stem cells (HFSCs) utilize glycolytic metabolism during their activation and anagen induction. However, the role of pyruvate kinase M2 (PKM2), which catalyzes the final step of glycolysis, in hair regeneration has not been elucidated. In this study, we investigated the expression pattern and activity of PKM2 during the depilation-induced anagen progression in mice. We found that TEPP-46, a selective activator of PKM2, enhanced hair re-growth and proliferation of HFSCs. PKM2 expression was increased via up-regulation of Wnt/β-catenin signaling, which is involved in hair regeneration. Moreover, a combined treatment with KY19382, a small molecule that activates Wnt/β-catenin signaling, and TEPP-46 significantly enhanced hair re-growth and wound-induced hair follicle neogenesis (WIHN). These results indicate that simultaneous activation of the PKM2 and Wnt/β-catenin signaling could be a potential strategy for treating alopecia patients.

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“…“Wnt” is coined as a combination of the name of the Drosophila segment polarity gene wingless and the name of the vertebrate homologue, integrated or int‐1 6 . Wnt signalling is a conserved pathway playing critical roles in multiple biologic processes including tissue regeneration in adults 7 . Wnt signalling consists of two main branches: the canonical and non‐canonical pathways.…”

Section: Wnt/β‐catenin Signallingmentioning

confidence: 99%

“…Taken together, most Wnt activators are still in their early stages of development. Their safety and efficacy profiles need to be confirmed 7 …”

Section: The Limitations Of β‐Catenin Activationmentioning

confidence: 99%

The possible role of Wnt/β‐catenin signalling in vitiligo treatment

Lin

Meng

Lin

2023

Acad Dermatol Venereol

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Vitiligo is a common chronic skin disease which has an adverse impact on patients' life. Its pathogenesis is complex, involving autoimmunity and oxidative stress (OS). Autoimmunity leads to the loss of epidermal melanocytes and the formation of the depigmented patches of the disease. Treatment of vitiligo should control the exaggerated immune response to arrest the progress of active disease, and then promote melanocytes to repigmentation. Wnt/β‐catenin signalling pathway has been of recent interest in vitiligo. Wnt/β‐catenin signalling pathway is downregulated in vitiligo. Upregulation of Wnt/β‐catenin signalling possibly control vitiligo autoimmune response by protecting melanocyte from OS damage, inhibiting CD8+ T cell effector cell differentiation and enhancing Treg. Wnt/β‐catenin signalling plays a critical role in the melanocyte regeneration by driving the differentiation of melanocyte stem cells (McSCs) into melanocytes. Promoting Wnt/β‐catenin signalling can not only arrest the progress of active disease of vitiligo but also promote repigmentation. Some of the main effective therapies for vitiligo are likely to work by activating Wnt/β‐catenin signalling. Agents that can enhance the effect of Wnt/β‐catenin signalling may become potential candidates for the development of new drugs for vitiligo treatment.

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Wnt signaling activation: targets and therapeutic opportunities for stem cell therapy and regenerative medicine

Abstract: Wnt proteins are secreted morphogens that play critical roles in embryonic development, stem cell proliferation, self-renewal, tissue regeneration and remodeling in adults. While aberrant Wnt signaling contributes to diseases such...

Cited by 19 publications

References 206 publications

Alpha terpineol directs bone marrow mesenchymal stem cells toward neuronal lineage through regulation of wnt signaling pathway

Alpha terpineol directs bone marrow mesenchymal stem cells toward neuronal lineage through regulation of wnt signaling pathway

Pyruvate Kinase M2 Promotes Hair Regeneration by Connecting Metabolic and Wnt/β-Catenin Signaling

The possible role of Wnt/β‐catenin signalling in vitiligo treatment

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