Enhancing maturity in 3D kidney micro-tissues through clonogenic cell combinations and endothelial integration.

As an advance laboratory model, three-dimensional (3D) organoid culture has recently been recruited to study development, physiology and abnormality of kidney tissue. Micro-tissues derived from primary renal cells are composed of 3D epithelial structures representing the main characteristics of original tissue. In this research, we presented a simple method to isolate mouse renal clonogenic mesenchymal (MLCs) and epithelial-like cells (ELCs).

Conditioned Media Derived from Human Adipose Tissue Mesenchymal Stromal Cells Improves Primary Hepatocyte Maintenance.

In this article which was published in Cell J, Vol 20, No 3, Autumn 2018, on pages 377-387, the scale bars in Figures 5-A missed unintentionally during production. The following figure is corrected. The authors would like to apologies for any inconvenience caused.

The emerging role of the long non-coding RNA HOTAIR in breast cancer development and treatment.

Despite considering vast majority of the transcribed molecules as merely noise RNA in the last decades, recent advances in the field of molecular biology revealed the mysterious role of long non-coding RNAs (lncRNAs), as a massive part of functional non-protein-coding RNAs. As a crucial lncRNA, HOX antisense intergenic RNA (HOTAIR) has been shown to participate in different processes of normal cell development. Aberrant overexpression of this lncRNA contributes to breast cancer progression, through different molecular mechanisms.

Kidney Regeneration: Stem Cells as a New Trend.

Renal disease is a major worldwide public health problem that affects one in ten people. Renal failure is caused by the irreversible loss of the structural and functional units of kidney (nephrons) due to acute and chronic injuries. In humans, new nephrons (nephrogenesis) are generated until the 36th week of gestation and no new nephron develops after birth.

Does HOTAIR expression level in the peripheral blood have veritably predictive/prognostic impact on breast cancer patients?

As a peripheral blood biomarker, the crucial role of long non-coding RNA (lncRNA) HOTAIR has recently been suggested in many types of disorder. Among these reports, few investigations have indicated overexpression of HOTAIR transcript in the breast cancer patients' peripheral blood. In this regard, we studied the potential impact of radiotherapy on the peripheral blood HOTAIR expression of different breast cancer patients.

Transplantation of Mouse Induced Pluripotent Stem Cell-Derived Podocytes in a Mouse Model of Membranous Nephropathy Attenuates Proteinuria.

Injury to podocytes is a principle cause of initiation and progression of both immune and non-immune mediated glomerular diseases that result in proteinuria and decreased function of the kidney. Current advances in regenerative medicine shed light on the therapeutic potential of cell-based strategies for treatment of such disorders. Thus, there is hope that generation and transplantation of podocytes from induced pluripotent stem cells (iPSCs), could potentially be used as a curative treatment for glomerulonephritis caused by podocytes injury and loss.

Histone Modification Marks Strongly Regulate CDH1 Promoter in Prostospheres as A Model of Prostate Cancer Stem Like Cells.

Objective: Cadherin-1 () plays an important role in the metastasis, while expression of this protein is under control of epigenetic changes on its gene promoter. Therefore we evaluated both DNA methylation (DNAmet) and histone modification marks of in prostate cancer stem like cells (PCSLCs).

Materials And Methods: In this experimental study, we isolated PCSLCs using cell surface marker and prostaspheroid formation, respectively.

Conditioned Media Derived from Human Adipose Tissue Mesenchymal Stromal Cells Improves Primary Hepatocyte Maintenance.

Objective: Recent advances in cell therapy have encouraged researchers to provide an alternative for treatment and restoration of damaged liver through using hepatocytes. However, these cells quickly lose their functional capabilities in vitro. Here, we aim to use the secretome of mesenchymal stromal cells (MSCs) to improve in vitro maintenance conditions for hepatocytes.

Unrestricted somatic stem cells, as a novel feeder layer: Ex vivo culture of human limbal stem cells.

Ex vivo culture of limbal stem cells (LSCs) is a current promising approach for reconstruction of the ocular surface. In this context, 3T3 feeder layer cells (mouse embryo fibroblast) are generally utilized to maintain and expand LSCs. The aim of this study is to develop a novel culture method (animal-derived products free) to expand LSCs, using umbilical cord derived human unrestricted somatic stem cells (hUSSCs) instead of 3T3 cell with an emphasis on maintaining of the Stemness in LSCs.

Reprogramming of somatic cells to induced neural stem cells.

Recent investigations have demonstrated that defined sets of exogenous factors (chemical and/or biochemical) can convert human and mouse somatic cells into induced neural stem cells (iNSCs). Considering the self-renewal and multi-potential differentiation capabilities of iNSCs, generation of these cells has considerably enhanced cell therapy for treatment of neurodegenerative disorders. These cells can also serve as models for investigation of the mechanism(s) underlying neurodegenerative diseases and as an asset in drug discovery.

A novel GAA-repeat-expansion-based mouse model of Friedreich's ataxia.

Friedreich's ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a GAA repeat expansion mutation within intron 1 of the FXN gene, resulting in reduced levels of frataxin protein. We have previously reported the generation of human FXN yeast artificial chromosome (YAC) transgenic FRDA mouse models containing 90-190 GAA repeats, but the presence of multiple GAA repeats within these mice is considered suboptimal. We now describe the cellular, molecular and behavioural characterisation of a newly developed YAC transgenic FRDA mouse model, designated YG8sR, which we have shown by DNA sequencing to contain a single pure GAA repeat expansion.

MutLα heterodimers modify the molecular phenotype of Friedreich ataxia.

Background: Friedreich ataxia (FRDA), the most common autosomal recessive ataxia disorder, is caused by a dynamic GAA repeat expansion mutation within intron 1 of FXN gene, resulting in down-regulation of frataxin expression. Studies of cell and mouse models have revealed a role for the mismatch repair (MMR) MutS-heterodimer complexes and the PMS2 component of the MutLα complex in the dynamics of intergenerational and somatic GAA repeat expansions: MSH2, MSH3 and MSH6 promote GAA repeat expansions, while PMS2 inhibits GAA repeat expansions.

Methodology/principal Findings: To determine the potential role of the other component of the MutLα complex, MLH1, in GAA repeat instability in FRDA, we have analyzed intergenerational and somatic GAA repeat expansions from FXN transgenic mice that have been crossed with Mlh1 deficient mice.

Generation and characterisation of Friedreich ataxia YG8R mouse fibroblast and neural stem cell models.

Background: Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disease caused by GAA repeat expansion in the first intron of the FXN gene, which encodes frataxin, an essential mitochondrial protein. To further characterise the molecular abnormalities associated with FRDA pathogenesis and to hasten drug screening, the development and use of animal and cellular models is considered essential. Studies of lower organisms have already contributed to understanding FRDA disease pathology, but mammalian cells are more related to FRDA patient cells in physiological terms.

Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model.

Friedreich's ataxia (FRDA) is the most common hereditary ataxia, affecting ∼3 in 100 000 individuals in Caucasian populations. It is caused by intronic GAA repeat expansions that hinder the expression of the FXN gene, resulting in defective levels of the mitochondrial protein frataxin. Sensory neurons in dorsal root ganglia (DRG) are particularly damaged by frataxin deficiency.

The mismatch repair system protects against intergenerational GAA repeat instability in a Friedreich ataxia mouse model.

Friedreich ataxia (FRDA) is an autosomal recessive neurodegenerative disorder caused by a dynamic GAA repeat expansion mutation within intron 1 of the FXN gene. Studies of mouse models for other trinucleotide repeat (TNR) disorders have revealed an important role of mismatch repair (MMR) proteins in TNR instability. To explore the potential role of MMR proteins on intergenerational GAA repeat instability in FRDA, we have analyzed the transmission of unstable GAA repeat expansions from FXN transgenic mice which have been crossed with mice that are deficient for Msh2, Msh3, Msh6 or Pms2.

Prolonged treatment with pimelic o-aminobenzamide HDAC inhibitors ameliorates the disease phenotype of a Friedreich ataxia mouse model.

Friedreich ataxia (FRDA) is an inherited neurodegenerative disorder caused by GAA repeat expansion within the FXN gene, leading to epigenetic changes and heterochromatin-mediated gene silencing that result in a frataxin protein deficit. Histone deacetylase (HDAC) inhibitors, including pimelic o-aminobenzamide compounds 106, 109 and 136, have previously been shown to reverse FXN gene silencing in short-term studies of FRDA patient cells and a knock-in mouse model, but the functional consequences of such therapeutic intervention have thus far not been described. We have now investigated the long-term therapeutic effects of 106, 109 and 136 in our GAA repeat expansion mutation-containing YG8R FRDA mouse model.