Biliary atresia-specific deciduous pulp stem cells feature biliary deficiency

Abstract Background Biliary atresia (BA) is a severe hepatobiliary disease in infants that ultimately results in hepatic failure; however, its pathological mechanism is poorly elucidated. Current surgical options, including Kasai hepatoportoenterostomy and orthotopic liver organ transplantations, are palliative; thus, innovation in BA therapy is urgent. Methods To examine whether BA-specific post-natal stem cells are feasible for autologous cell source for BA treatment, we isolated from human exfoliated deciduous teeth, namely BA-SHED, using a standard colony-forming unit fibroblast (CFU-F) method and compared characteristics as mesenchymal stem cells (MSCs) to healthy donor-derived control SHED, Cont-SHED. BA-SHED and Cont-SHED were intrasplenically transplanted into chronic carbon tetrachloride (CCl4)-induced liver fibrosis model mice, followed by the analysis of bile drainage function and donor integration in vivo. Immunohistochemical assay was examined for the regeneration of intrahepatic bile ducts in the recipient’s liver using anti-human specific keratin 19 (KRT19) antibody. Results BA-SHED formed CFU-F, expressed MSC surface markers, and exhibited in vitro mesenchymal multipotency similar to Cont-SHED. BA-SHED showed less in vitro hepatogenic potency than Cont-SHED. Cont-SHED represented in vivo bile drainage function and KRT19-positive biliary regeneration in chronic carbon tetrachloride-induced liver fibrosis model mice. BA-SHED failed to show in vivo biliary potency and bile drainage function compared to Cont-SHED. Conclusion These findings indicate that BA-SHED are not feasible source for BA treatment, because BA-SHED may epigenetically modify the underlying prenatal and perinatal BA environments. In conclusion, these findings suggest that BA-SHED-based studies may provide a platform for understanding the underlying molecular mechanisms of BA development and innovative novel modalities in BA research and treatment.

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Expression Profile of New Marker Genes Involved in Differentiation of Canine Adipose-Derived Stem Cells into Osteoblasts

International Journal of Molecular Sciences ◽

10.3390/ijms22136663 ◽

2021 ◽

Vol 22 (13) ◽

pp. 6663

Author(s):

Maurycy Jankowski ◽

Mariusz Kaczmarek ◽

Grzegorz Wąsiatycz ◽

Claudia Dompe ◽

Paul Mozdziak ◽

...

Keyword(s):

Stem Cells ◽

In Vitro Culture ◽

Osteogenic Differentiation ◽

Molecular Mechanisms ◽

Marker Genes ◽

P Value ◽

Illumina Platform

Next-generation sequencing (RNAseq) analysis of gene expression changes during the long-term in vitro culture and osteogenic differentiation of ASCs remains to be important, as the analysis provides important clues toward employing stem cells as a therapeutic intervention. In this study, the cells were isolated from adipose tissue obtained during routine surgical procedures and subjected to 14-day in vitro culture and differentiation. The mRNA transcript levels were evaluated using the Illumina platform, resulting in the detection of 19,856 gene transcripts. The most differentially expressed genes (fold change >|2|, adjusted p value < 0.05), between day 1, day 14 and differentiated cell cultures were extracted and subjected to bioinformatical analysis based on the R programming language. The results of this study provide molecular insight into the processes that occur during long-term in vitro culture and osteogenic differentiation of ASCs, allowing the re-evaluation of the roles of some genes in MSC progression towards a range of lineages. The results improve the knowledge of the molecular mechanisms associated with long-term in vitro culture and differentiation of ASCs, as well as providing a point of reference for potential in vivo and clinical studies regarding these cells’ application in regenerative medicine.

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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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CSIG-30. miR-146a INHIBITS TUMORIGENESIS AND INDUCES TEMOZOLOMIDE SENSITIVITY VIA AFFECTING CANCER STEM CELL PROPERTIES IN GBM

Neuro-Oncology ◽

10.1093/neuonc/noz175.200 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi50-vi50

Author(s):

Tiantian Cui ◽

Erica Hlavin Bell ◽

Joseph McElroy ◽

Kevin Liu ◽

Pooja Manchanda Gulati ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Cancer Stem Cell ◽

Molecular Mechanisms ◽

Functional Studies ◽

Average Survival ◽

Novel Biomarkers ◽

The Ohio State University

Abstract BACKGROUND Glioblastomas (GBMs) are the most aggressive primary brain tumors, with an average survival time of less than 15 months. miRNAs are emerging as promising and novel biomarkers in GBM. The aims of this study are: 1) to investigate novel miRNAs biomarkers that affect tumorigenesis and therapeutic sensitivity, and 2) to study the underlying molecular mechanisms in GBM. METHODS Nanostring v3 was performed followed by univariable (UVA) and multivariable (MVA) analyses. Functional studies were conducted to define the role of miR-146a in GBM tumorigenesis and therapeutic response and the molecular mechanisms were investigated. RESULTS UVA analyses demonstrated that miR-146a is one of the top miRNAs that correlated with better prognosis in GBM patients (p=9.21E-05), which was independent of MGMT promoter methylation by MVA analyses (p< 0.001). miR-146a expression was significantly downregulated in recurrent GBM tumors compared with the paired primary GBM tumors (p=0.003). Overexpression of miR-146a significantly inhibited tumor cell growth and sensitized patient-derived primary GBM cells to temozolomide (TMZ) treatment in vitro, and showed statistically significant smaller tumor size (p< 0.01) and prolonged survival (p=0.001) in vivo. In addition, miR-146a is downregulated in glioma cancer stem cells, and overexpression of miR-146a significantly affected glioma cancer stem cell self-renewal. We also found that overexpression of miR-146a significantly inhibited the NF-κB, AKT, and ERK pathways. CONCLUSION Our data suggest, for the first time, that miR-146a predicts favorable prognosis for GBM patients and sensitizes primary GBM cells to TMZ treatment in vitro and in vivo through regulating glioma stem cells. Importantly, miR-146a may prove to be a master switch shutting off AKT, NF-κB, as well as other pathways and may overcome redundancies among these pathways leading to resistance. FUNDING: Bohnenn Fund (to PR), R01CA108633, R01CA169368, U10CA180850-01(NCI), Brain Tumor Funders Collaborative Grant, and The Ohio State University CCC (all to AC).

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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 Effect of Lecithins Coupled Decorin Nanoliposomes on Treatment of Carbon Tetrachloride-Induced Liver Fibrosis

BioMed Research International ◽

10.1155/2020/8815904 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Guojun Chen ◽

Yiping Zhu ◽

Xiao Liang ◽

Xianfa Wang ◽

Weihua Yu ◽

...

Keyword(s):

Cell Proliferation ◽

Carbon Tetrachloride ◽

Bile Duct ◽

Liver Fibrosis ◽

Western Blot ◽

Immunofluorescence Staining ◽

Type I ◽

Masson Trichrome Staining

This study aimed to investigate the effect of bile duct-targeting lecithins- (PC-) coupled decorin (DCN) (PC-DCN) nanoliposomes against liver fibrosis in vitro and in vivo. We prepared PC-DCN nanoliposomes by using rat astrocytes, HSC-T6, to verify the antifibrosis effect of PC-DCN in vitro. First, we established a rat model of carbon tetrachloride-induced fibrosis. PC-DCN nanoliposomes were then injected into fibrotic rats via the portal vein or bile duct. The EdU assay was performed to analyze cell proliferation. Immunofluorescence staining was used to detect α-smooth muscle actin (α-SMA) expression. Western blot was performed to examine the expression of α-SMA, collagen type I alpha 1 (COL1A1), and transforming growth factor-β (TGF-β) protein. The levels of aspartate transaminase (AST), alanine transaminase (ALT), and total bilirubin (TBIL) were examined by enzyme-linked immunosorbent assay (ELISA) analysis. Hematoxylin and eosin (H&E) staining and Masson trichrome staining were used to determine liver tissue lesions and liver fibrosis. Compared with TGF-β group, PC-DCN treatment could significantly reduce cell proliferation. Western blot analysis indicated that the expression of α-SMA, COL1A1, and TGF-β was downregulated after treatment with PC-DCN in vitro and in vivo. Immunofluorescence staining confirmed that α-SMA expression was reduced by PC-DCN. Furthermore, H&E staining and Masson trichrome staining showed that the administration of PC-DCN nanoliposomes via the bile duct could reduce the extent of liver fibrosis. PCR analysis showed that PC-DCN administration could reduce proinflammatory cytokines IL-6, TNF-α, and IL-1β expression via the bile duct. The administration of PC-DCN nanoliposomes also significantly downregulated liver function indicators ALT, AST, and TBIL. The results of our study indicated that PC-DCN could effectively reduce the extent of liver fibrosis.

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Steel factor coordinately regulates the molecular signature and biologic function of hematopoietic stem cells

Blood ◽

10.1182/blood-2007-10-117820 ◽

2008 ◽

Vol 112 (3) ◽

pp. 560-567 ◽

Cited By ~ 40

Author(s):

David G. Kent ◽

Brad J. Dykstra ◽

Jay Cheyne ◽

Elaine Ma ◽

Connie J. Eaves

Keyword(s):

Stem Cells ◽

Hematopoietic Stem Cells ◽

Molecular Mechanisms ◽

Molecular Signature ◽

Hematopoietic Stem ◽

Steel Factor ◽

Biologic Function

Abstract Hematopoietic stem cells (HSCs) regenerated in vivo display sustained differences in their self-renewal and differentiation activities. Variations in Steel factor (SF) signaling are known to affect these functions in vitro, but the cellular and molecular mechanisms involved are not understood. To address these issues, we evaluated highly purified HSCs maintained in single-cell serum-free cultures containing 20 ng/mL IL-11 plus 1, 10, or 300 ng/mL SF. Under all conditions, more than 99% of the cells traversed a first cell cycle with similar kinetics. After 8 hours in the 10 or 300 ng/mL SF conditions, the frequency of HSCs remained unchanged. However, in the next 8 hours (ie, 6 hours before any cell divided), HSC integrity was sustained only in the 300 ng/mL SF cultures. The cells in these cultures also contained significantly higher levels of Bmi1, Lnk, and Ezh2 transcripts but not of several other regulators. Assessment of 21 first division progeny pairs further showed that only those generated in 300 ng/mL SF cultures contained HSCs and pairs of progeny with similar differentiation programs were not observed. Thus, SF signaling intensity can directly and coordinately alter the transcription factor profile and long-term repopulating ability of quiescent HSCs before their first division.

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SIRT1 regulates sphingolipid metabolism and neural differentiation of mouse embryonic stem cells through c-Myc- SMPDL3B

10.1101/2021.02.24.432815 ◽

2021 ◽

Author(s):

Wei Fan ◽

Shuang Tang ◽

Xiaojuan Fan ◽

Yi Fang ◽

Xiaojiang Xu ◽

...

Keyword(s):

Stem Cells ◽

Embryonic Stem Cells ◽

Neural Differentiation ◽

Transcriptional Control ◽

Molecular Mechanisms ◽

Embryonic Stem ◽

Mouse Embryonic Stem Cells ◽

Sphingolipid Metabolism

AbstractSphingolipids are important structural components of cell membranes and prominent signaling molecules controlling cell growth, differentiation, and apoptosis. Sphingolipids are particularly abundant in the brain, and defects in sphingolipid degradation are associated with several human neurodegenerative diseases. However, molecular mechanisms governing sphingolipid metabolism remain unclear. Here we report that sphingolipid degradation is under transcriptional control of SIRT1, a highly conserved mammalian NAD+-dependent protein deacetylase, in mouse embryonic stem cells (mESCs). Deletion of SIRT1 results in accumulation of sphingomyelin in mESCs, primarily due to reduction of SMPDL3B, a GPI-anchored plasma membrane bound sphingomyelin phosphodiesterase. Mechanistically, SIRT1 regulates transcription of Smpdl3b through c-Myc. Functionally, SIRT1 deficiency-induced accumulation of sphingomyelin increases membrane fluidity and impairs neural differentiation in vitro and in vivo. Our findings discover a key regulatory mechanism for sphingolipid homeostasis and neural differentiation, further imply that pharmacological manipulation of SIRT1-mediated sphingomyelin degradation might be beneficial for treatment of human neurological diseases.

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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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Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice

Stem Cells International ◽

10.1155/2015/747245 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 12

Author(s):

Sulaiman Shams ◽

Sadia Mohsin ◽

Ghazanfar Ali Nasir ◽

Mohsin Khan ◽

Shaheen N. Khan

Keyword(s):

Stem Cells ◽

Liver Fibrosis ◽

Liver Injury ◽

Therapeutic Potential ◽

Direct Injection ◽

Glycogen Storage ◽

Pretreated Group ◽

Mouse Hepatocytes

Stem cells have opened a new avenue to treat liver fibrosis. We investigated in vitro and in vivo the effect of cytokine (HGF and FGF4) pretreated MSCs in reduction of CCl4liver injury. Mouse MSCs were pretreated with cytokines to improve their ability to reduce CCl4injury. In vitro we gave CCl4injury to mouse hepatocytes and cocultured it with untreated and cytokines pretreated MSCs. For in vivo study we labeled MSCs with PKH-26 and transplanted them into CCl4injured mice by direct injection into liver. In vitro data showed that cytokines pretreated MSCs significantly reduce LDH level and apoptotic markers in CCl4injured hepatocytes cocultured model. Furthermore the cytokines pretreated MSCs also improved cell viability and enhanced hepatic and antiapoptotic markers in injured hepatocytes cocultured model as compared to untreated MSCs. In vivo data in cytokines pretreated group demonstrated greater homing of MSCs in liver, restored glycogen storage, and significant reduction in collagen, alkaline phosphatase, and bilirubin levels. TUNEL assay and real time PCR also supported our hypothesis. Therefore, cytokines pretreated MSCs were shown to have a better therapeutic potential on reduction of liver injury. These results demonstrated the potential utility of this novel idea of cytokines pretreated MSCs for the treatment of liver fibrosis.

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