Rapid and Efficient Direct Conversion of Human Adult Somatic Cells into Neural Stem Cells by HMGA2/let-7b.

A recent study has suggested that fibroblasts can be converted into mouse-induced neural stem cells (miNSCs) through the expression of defined factors. However, successful generation of human iNSCs (hiNSCs) has proven challenging to achieve. Here, using microRNA (miRNA) expression profile analyses, we showed that let-7 microRNA has critical roles for the formation of PAX6/NESTIN-positive colonies from human adult fibroblasts and the proliferation and self-renewal of hiNSCs.

Core-shell nanoparticle controlled hATSCs neurogenesis for neuropathic pain therapy.

A stem cell-based strategy for tissue engineering in regenerative medicine is crucial to produce and effective therapeutic replacement of injured or damaged tissues. This type of therapeutic replacement requires interaction with the cells and tissues via the incorporation of a beneficial physical microenvironment and cellular biochemical signals. Recently, we studied a cell-function modifying factor, core-shell nanoparticles consisting of an SPIO (superparamagnetic iron oxide) core covered with a photonic ZnO shell for human adipose tissue-derived stem cells (hATSCs) that regulate various cellular functions: self-renewal, neurogenesis, and dedifferentiation.

MBD6 is a direct target of Oct4 and controls the stemness and differentiation of adipose tissue-derived stem cells.

Argonaute 2 (Ago2) is a pivotal regulator of cell fate in adult stem cells. Its expression is significantly downregulated in late passages of cells, concomitant with a prominent increase in Ago2 cytosolic localization in single cells. Nuclear localization of Ago2 is crucial for the survival, proliferation, and differentiation of hATSCs (human adipose tissue-derived stem cells), mediated by the specific binding of the regulatory regions of functional genes, which positively or negatively altered gene expression.

MicroRNA 486 is a potentially novel target for the treatment of spinal cord injury.

MicroRNAs have been shown to effectively regulate gene expression at the translational level. Recently, we identified novel microRNAs that were upregulated in a mouse model of spinal cord injury. Among those, we have focused on microRNA 486, which directly represses NeuroD6 expression through a conserved sequence in its untranslated region.

Novel GSK-3β inhibitors and CBM-1078 guide hATSCs' deaging via Oct4 and β-catenin activation.

Unlabelled: Abstract Aims: The fate decision of adult stem cells is determined by the activation of specific intracellular signaling pathways after exposure to specific stimuli. In this study, we demonstrated specific functions of a novel small molecule, CBM-1078, that induced cell self-renewal via Oct4- and canonical Wnt/β-catenin-mediated deaging in cultured human adipose tissue-derived stem cells (hATSCs).

Results: As a potential glycogen synthase kinase-3β (GSK-3β) inhibitor, CBM-1078 primarily activated β-catenin and Oct4 expression after inhibition of GSK-3β.

Silencing of miR20a is crucial for Ngn1-mediated neuroprotection in injured spinal cord.

MicroRNAs (miRNAs) compose a relatively new discipline in biomedical research, and many physiological processes in disease have been associated with changes in miRNA expression. Several studies report that miRNAs participate in biological processes such as the control of secondary injury in several disease models. Recently, we identified novel miRNAs that were abnormally up-regulated in a traumatic spinal cord injury (SCI).

miR23b ameliorates neuropathic pain in spinal cord by silencing NADPH oxidase 4.

Aims: Neuropathic pain is a well-known type of chronic pain caused by damage to the nervous system. Until recently, researchers have been primarily focused on identifying the cellular or chemical sources of neuropathic pain or have approached neuropathic pain via the basis of biological study. We investigated whether mmu-mir-23b (miR23b) infusion can alleviate pain by compensating for the abnormally downregulated miR23b by reducing the expression of its target gene, NADPH oxidase 4 (NOX4), a reactive oxygen species (ROS) family member overexpressed in neuropathic pain.

Human umbilical cord blood-derived mesenchymal stem cells protect against neuronal cell death and ameliorate motor deficits in Niemann Pick type C1 mice.

Niemann Pick disease type C1 (NPC) is an autosomal recessive disease characterized by progressive neurological deterioration leading to premature death. In this study, we hypothesized that human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) have the multifunctional abilities to ameliorate NPC symptoms in the brain. To test this hypothesis, hUCB-MSCs were transplanted into the hippocampus of NPC mice in the early asymptomatic stage.

Vascular endothelial growth factor/kinase insult domain receptor (KDR)/fetal liver kinase 1 (FLK1)-mediated skin-epithelial progenitor cells reprogramming.

Vascular endothelial growth factor (VEGF) is an angiogenic protein that has effects on damaged neurons. We investigated VEGF function and found that it effectively induces the transition of skin-derived epithelial progenitor cells (EPCs) to more primitive stem cells. This change was accompanied by the epigenetic reprogramming of many genes.

DHP-derivative and low oxygen tension effectively induces human adipose stromal cell reprogramming.

Background And Methods: In this study, we utilized a combination of low oxygen tension and a novel anti-oxidant, 4-(3,4-dihydroxy-phenyl)-derivative (DHP-d) to directly induce adipose tissue stromal cells (ATSC) to de-differentiate into more primitive stem cells. De-differentiated ATSCs was overexpress stemness genes, Rex-1, Oct-4, Sox-2, and Nanog. Additionally, demethylation of the regulatory regions of Rex-1, stemnesses, and HIF1alpha and scavenging of reactive oxygen species were finally resulted in an improved stem cell behavior of de-differentiate ATSC (de-ATSC).

Regulation of adipose tissue stromal cells behaviors by endogenic Oct4 expression control.

Background: To clarify the role of the POU domain transcription factor Oct4 in Adipose Tissue Stromal Cells (ATSCs), we investigated the regulation of Oct4 expression and other embryonic genes in fully differentiated cells, in addition to identifying expression at the gene and protein levels. The ATSCs and several immature cells were routinely expressing Oct4 protein before and after differentiating into specific lineages.

Methodology/principal Findings And Conclusions: Here, we demonstrated the role of Oct4 in ATSCs on cell proliferation and differentiation.

IFATS collection: Selenium induces improvement of stem cell behaviors in human adipose-tissue stromal cells via SAPK/JNK and stemness acting signals.

In the present study, the potential of selenium to enhance stem cell behavior through improvement of human adipose tissue-derived stromal cells (ATSCs) and the associated molecular mechanism was evaluated. Selenium-induced improvement in stem cell behavior of human ATSCs caused expression of several genes, indicating downregulated mature cell marker proteins coupled with increased cell growth and telomerase activities after the overexpression of Rex1, Nanog, OCT4, SOX2, KLF4, and c-Myc. Also, selenium-treated ATSCs significantly downregulated p53 and p21 tumor suppressor gene products.