In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice

: Most conventional treatments for neurodegenerative diseases fail due to their focus on neuroprotection rather than neurorestoration. Stem cell‐based therapies are becoming a potential treatment option for neurodegenerative diseases as they can home in, engraft, differentiate and produce factors for CNS recovery. Stem cells derived from human dental pulp tissue differ from other sources of mesenchymal stem cells due to their embryonic neural crest origin and neurotrophic property. These include both dental pulp stem cells [DPSCs] from dental pulp tissues of human permanent teeth and stem cells from human exfoliated deciduous teeth [SHED]. SHED offer many advantages over other types of MSCs such as good proliferative potential, minimal invasive procurement, neuronal differentiation and neurotrophic capacity, and negligible ethical concerns. The therapeutic potential of SHED is attributed to the paracrine action of extracellularly released secreted factors, specifically the secretome, of which exosomes is a key component. SHED and its conditioned media can be effective in neurodegeneration through multiple mechanisms, including cell replacement, paracrine effects, angiogenesis, synaptogenesis, immunomodulation, and apoptosis inhibition, and SHED exosomes offer an ideal refined bed-to-bench formulation in neurodegenerative disorders. However, in spite of these advantages, there are still some limitations of SHED exosome therapy, such as the effectiveness of long-term storage of SHED and their exosomes, the development of a robust GMP-grade manufacturing protocol, optimization of the route of administration, and evaluation of the efficacy and safety in humans. In this review, we have addressed the isolation, collection and properties of SHED along with its therapeutic potential on in vitro and in vivo neuronal disorder models as evident from the published literature.

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Therapeutic potential of stem cells from human exfoliated deciduous teeth infusion into patients with type 2 diabetes depends on basal lipid levels and islet function

Stem Cells Translational Medicine ◽

10.1002/sctm.20-0303 ◽

2021 ◽

Author(s):

Wenwen Li ◽

Xuan Jiao ◽

Jingyun Song ◽

Bingdong Sui ◽

Zhili Guo ◽

...

Keyword(s):

Type 2 Diabetes ◽

Stem Cells ◽

Therapeutic Potential ◽

Deciduous Teeth ◽

Islet Function ◽

Lipid Levels ◽

Human Exfoliated Deciduous Teeth

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In vitro and in vivo characteristics of stem cells from human exfoliated deciduous teeth obtained by enzymatic disaggregation and outgrowth

Archives of Oral Biology ◽

10.1016/j.archoralbio.2014.06.002 ◽

2014 ◽

Vol 59 (10) ◽

pp. 1013-1023 ◽

Cited By ~ 20

Author(s):

Mijeong Jeon ◽

Je Seon Song ◽

Byung-Jai Choi ◽

Hyung-Jun Choi ◽

Dong-Min Shin ◽

...

Keyword(s):

Stem Cells ◽

Deciduous Teeth ◽

Human Exfoliated Deciduous Teeth

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Stem Cells from Human Exfoliated Deciduous Teeth (SHED) Differentiate in vivo and Promote Facial Nerve Regeneration

Cell Transplantation ◽

10.1177/0963689718809090 ◽

2018 ◽

Vol 28 (1) ◽

pp. 55-64 ◽

Cited By ~ 6

Author(s):

Larissa Vilela Pereira ◽

Ricardo Ferreira Bento ◽

Dayane B. Cruz ◽

Cláudia Marchi ◽

Raquel Salomone ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Schwann Cell ◽

Facial Nerve ◽

Deciduous Teeth ◽

Control Group ◽

Cell Marker ◽

Mandibular Branch ◽

Human Exfoliated Deciduous Teeth

Post-traumatic lesions with transection of the facial nerve present limited functional outcome even after repair by gold-standard microsurgical techniques. Stem cell engraftment combined with surgical repair has been reported as a beneficial alternative. However, the best association between the source of stem cell and the nature of conduit, as well as the long-term postoperative cell viability are still matters of debate. We aimed to assess the functional and morphological effects of stem cells from human exfoliated deciduous teeth (SHED) in polyglycolic acid tube (PGAt) combined with autografting of rat facial nerve on repair after neurotmesis. The mandibular branch of rat facial nerve submitted to neurotmesis was repaired by autograft and PGAt filled with purified basement membrane matrix with or without SHED. Outcome variables were compound muscle action potential (CMAP) and axon morphometric. Animals from the SHED group had mean CMAP amplitudes and mean axonal diameters significantly higher than the control group ( p < 0.001). Mean axonal densities were significantly higher in the control group ( p = 0.004). The engrafted nerve segment resected 6 weeks after surgery presented cells of human origin that were positive for the Schwann cell marker (S100), indicating viability of transplanted SHED and a Schwann cell-like phenotype. We conclude that regeneration of the mandibular branch of the rat facial nerve was improved by SHED within PGAt. The stem cells integrated and remained viable in the neural tissue for 6 weeks since transplantation, and positive labeling for S100 Schwann-cell marker suggests cells initiated in vivo differentiation.

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Stem cells from human exfoliated deciduous teeth correct the immune imbalance of allergic rhinitis via Treg cells in vivo and in vitro

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1134-z ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 9

Author(s):

Yu-Yang Dai ◽

Si-Yang Ni ◽

Ke Ma ◽

Yu-Shi Ma ◽

Zhi-Shi Wang ◽

...

Keyword(s):

Stem Cells ◽

Allergic Rhinitis ◽

Treg Cells ◽

Deciduous Teeth ◽

Immune Imbalance ◽

Human Exfoliated Deciduous Teeth

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The Anti-fibrotic Effect of Human Fetal Skin-derived Stem Cell Secretome on the Liver Fibrosis

10.21203/rs.3.rs-39850/v1 ◽

2020 ◽

Author(s):

Xia Yao ◽

Jing Wang ◽

Jiajing Zhu ◽

Xiaoli Rong

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Fetal Skin ◽

Mesenchymal Transition ◽

Cell Based Therapy ◽

Causes Of Mortality ◽

Smad7 Expression

Abstract Background: Liver fibrosis resulting from chronic liver injury is one of the major causes of mortality worldwide. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease, while maintaining its advantages.Methods: In this study, we investigated the effect ofhuman fetal skin-derived stem cells (hFFSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFFSCssecretome in liver fibrosis, we established the CCl4-induced rat liver fibrosis model, and administered hFFSCssecretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFFSCssecretome in hepatic stellate cells (HSCs).Results: Our results showed that hFFSCssecretomeffectively reduced collagen content in liver, improved the liver function and promoted liver regeneration. Interestingly, we also found thathFFSCssecretom reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSCsecretom inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, however, increased Smad7 expression.Conclusions: In conclusions, our results suggest that hFFSCssecretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

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3D hESC exosomes enriched with miR-6766-3p ameliorates liver fibrosis by attenuating activated stellate cells through targeting the TGFβRII-SMADS pathway

10.21203/rs.3.rs-736691/v1 ◽

2021 ◽

Author(s):

Ning Wang ◽

Xiajing Li ◽

Zhiyong Zhong ◽

Yaqi Qiu ◽

Shoupei Liu ◽

...

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Liver Injury ◽

Cell Activation ◽

Therapeutic Potential ◽

Stellate Cell ◽

Embryonic Stem ◽

Luciferase Reporter ◽

Fibrotic Liver

Abstract BackgroundExosomes secreted from stem cells exerted salutary effects on the fibrotic liver. Herein, the roles of exosomes derived from human embryonic stem cell (hESC) in anti-fibrosis were extensively investigated. Compared with two-dimensional (2D) culture, the clinical and biological relevance of three-dimensional (3D) cell spheroids were greater because of their higher regeneration potential since they behave more like cells in vivo. In our study, exosomes derived from 3D human embryonic stem cells (hESC) spheroids and the monolayer (2D) hESCs were collected and compared the therapeutic potential for fibrotic liver in vitro and in vivo. ResultsIn vitro, PKH26 labled-hESC-Exosomes were shown to be internalized and integrated into TGFβ-activated-LX2 cells, and reduced the expression of profibrogenic markers, thereby regulating cellular phenotypes. TPEF imaging indicated that PKH26-labled-3D-hESC-Exsomes possessed an enhanced capacity to accumulate in the livers and exhibited more dramatic therapeutic potential in the injured livers of fibrosis mouse model. 3D-hESC-Exosomes decreased profibrogenic markers and liver injury markers, and improved the level of liver functioning proteins, eventually restoring liver function of fibrosis mice. miRNA array revealed a significant enrichment of miR-6766-3p in 3D-hESC-Exosomes, moreover, bioinformatics and dual luciferase reporter assay identified and confirmed the TGFβRII gene as the target of miR-6766-3p. Furthermore, the delivery of miR-6766-3p into activated-LX2 cells decreased cell proliferation, chemotaxis and profibrotic effects, and further investigation demonstrated that the expression of target gene TGFβRII and its downstream SMADs proteins, especially phosphorylated protein p-SMAD2/3 was also notably down-regulated by miR-6766-3p. These findings unveiled that miR-6766-3p in 3D-hESC-Exosomes inactivated SMADs signaling by inhibiting TGFβRII expression, consequently attenuating stellate cell activation and suppressing liver fibrosis. ConclusionsOur results showed that miR-6766-3p in the 3D-hESC-Exosomes inactivates smads signaling by restraining TGFβRII expression, attenuated LX2 cell activation and suppressed liver fibrosis, suggesting that 3D-hESC-Exosome enriched-miR6766-3p is a novel anti-fibrotic therapeutics for treating chronic liver disease. These results also proposed a significant strategy that 3D-Exo could be used as natural nanoparticles to rescue liver injury via delivering antifibrotic miR-6766-3p.

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Human fetal skin-derived stem cell secretome reduce liver fibrosis

10.21203/rs.3.rs-19079/v2 ◽

2020 ◽

Author(s):

Xia Yao ◽

Jing Wang ◽

Jiajing Zhu ◽

Xiaoli Rong

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Epithelial Mesenchymal Transition ◽

Therapeutic Potential ◽

Fetal Skin ◽

Mesenchymal Transition ◽

Cell Based Therapy ◽

Current Therapies ◽

Causes Of Mortality

Abstract Background: Liver fibrosis resulting from a chronic liver injury is one of the significant causes of mortality. Stem cells-secreted secretome has been evaluated for overcoming the limitations of cell-based therapy in hepatic disease while maintaining its advantages over the current therapies. Methods: In this study, we investigated the effect of human fetal skin-derived stem cells (hFSSCs) secretome in the treatment of liver fibrosis. To determine the therapeutic potential of the hFSSCs secretome in liver fibrosis, we established the CCl4-induced liver fibrosis rat model, and we administered hFSSCs secretome in vivo. Moreover, we investigated the anti-fibrotic mechanism of hFSSCs secretome in hepatic stellate cells (HSCs). Results: Our results showed that hFSSCs secretome effectively reduced collagen content in the liver, and improved the liver function and promoted liver regeneration. Interestingly, we also found that hFSSCs secretome reduced liver fibrosis through suppressing the epithelial-mesenchymal transition (EMT) process. In addition, we found that hFSSC secretome inhibited the TGF-β1, Smad2, Smad3, and Collagen I expression, while we observed, increased Smad7 expression. Conclusions: In conclusion, our results suggest that hFSSCs secretome treatment could reduce CCl4-induced liver fibrosis via regulating the TGF-β/Smad signal pathway.

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Stem Cells of Dental Origin: Current Research Trends and Key Milestones towards Clinical Application

Stem Cells International ◽

10.1155/2016/4209891 ◽

2016 ◽

Vol 2016 ◽

pp. 1-20 ◽

Cited By ~ 33

Author(s):

Athina Bakopoulou ◽

Imad About

Keyword(s):

Stem Cells ◽

Well Being ◽

Biological Properties ◽

Deciduous Teeth ◽

Regenerative Dentistry ◽

Dental Origin ◽

Apical Papilla ◽

Human Exfoliated Deciduous Teeth

Dental Mesenchymal Stem Cells (MSCs), including Dental Pulp Stem Cells (DPSCs), Stem Cells from Human Exfoliated Deciduous teeth (SHED), and Stem Cells From Apical Papilla (SCAP), have been extensively studied using highly sophisticatedin vitroandin vivosystems, yielding substantially improved understanding of their intriguing biological properties. Their capacity to reconstitute various dental and nondental tissues and the inherent angiogenic, neurogenic, and immunomodulatory properties of their secretome have been a subject of meticulous and costly research by various groups over the past decade. Key milestone achievements have exemplified their clinical utility in Regenerative Dentistry, as surrogate therapeutic modules for conventional biomaterial-based approaches, offering regeneration of damaged oral tissues instead of simply “filling the gaps.” Thus, the essential next step to validate these immense advances is the implementation of well-designed clinical trials paving the way for exploiting these fascinating research achievements for patient well-being: the ultimate aim of this ground breaking technology. This review paper presents a concise overview of the major biological properties of the human dental MSCs, critical for the translational pathway “from bench to clinic.”

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