Stem Cells International

The transcription factor Brn4 exhibits vital roles in the embryonic development of the neural tube, inner ear, pancreas islet, and neural stem cell differentiation. Our previous studies have shown that Brn4 promotes neuronal differentiation of hippocampal neural stem cells (NSCs). However, its mechanism is still unclear. Here, starting from the overlapping genes between RNA-seq and ChIP-seq results, we explored the downstream target genes that mediate Brn4-induced hippocampal neurogenesis. There were 16 genes at the intersection of RNA-seq and ChIP-seq, among which the Lama2 and Samsn1 levels can be upregulated by Brn4, and the combination between their promoters and Brn4 was further determined using ChIP and dual luciferase reporter gene assays...

According to strong evidence, diabetes mellitus increases the risk of cognitive impairment. Mesenchymal stem cells have been shown to be potential therapeutic agents for neurological disorders. In the current study, we aimed to examine the effects of Wharton's jelly-derived mesenchymal stem cell-conditioned medium (WJMSC-CM) on learning and memory, oxidative stress, apoptosis, and histological changes in the hippocampus of diabetic rats. Randomly, 35 male Sprague Dawley rats weighing 260-300 g were allocated into five groups: control, diabetes, and three diabetic groups treated with insulin, WJMSC-CM, and DMEM...

Autophagy plays an important role in the pluripotency and differentiation of stem cells. Transcriptome data showed that the autophagy genes MAP1LC3A and MAP1LC3B were significantly upregulated in primordial germ cells (PGCs). The Kyoto Encyclopedia of Genes and Genome (KEGG) results showed that the lysosome signaling pathway, which is related to autophagy, was significantly enriched in PGCs. Quantitative RT-PCR, western blotting, and transmission electron microscopy (TEM) results showed that autophagy was expressed in both embryonic stem cells (ESCs) and PGCs but was significantly activated in PGCs...

As double membrane-encapsulated nanovesicles (30-150 nm), exosomes (Exos) shuttle between different cells to mediate intercellular communication and transport active cargoes of paracrine factors. The anti-inflammatory and immunomodulatory activities of mesenchymal stem cell (MSC)-derived Exos (MSC-Exos) provide a rationale for novel cell-free therapies for inflammatory bowel disease (IBD). Growing evidence has shown that MSC-Exos can be a potential candidate for treating IBD. In the present review, we summarized the most critical advances in the properties of MSC-Exos, provided the research progress of MSC-Exos in treating IBD, and discussed the molecular mechanisms underlying these effects...

Diabetic nephropathy (DN) is one of the microvascular complications of diabetes. Recent studies suggest that the pyroptosis of renal tubular epithelial cell plays a critical role in DN. Currently, effective therapeutic strategies to counteract and reverse the progression of DN are lacking. Mesenchymal stem cells (MSCs) represent an attractive therapeutic tool for tissue damage and inflammation owing to their unique immunomodulatory properties. However, the underlying mechanisms remain largely unknown. In the present study, we found that human umbilical cord MSCs (UC-MSCs) can effectively ameliorate kidney damage and reduce inflammation in DN rats...

Type II alveolar epithelial cell (AECII) apoptosis is one of the most vital causes of sepsis-induced acute respiratory distress syndrome (ARDS). Recent evidence has proved that bone mesenchymal stem cell-derived exosomes (BMSC-exos) can effectively reduce sepsis-induced ARDS. However, the function and molecular mechanism of BMSC-exos in sepsis-induced AECII apoptosis remain to be elucidated. In the present study, a more significant number of AECII apoptosis, high mitochondrial fission p-Drp1 protein levels, and low levels of mitochondrial biogenesis-related PGC1 α , Tfam, and Nrf1 proteins accompanied with ATP content depression were confirmed in AECIIs in response to sepsis...

Human bone marrow-derived mesenchymal stem cells (hBMSCs) are promising candidates for stem cell therapy in clinical trials. Applications of hBMSCs in clinical therapy are limited by cellular senescence due to long-term ex vivo expansion. Metformin, an oral hypoglycemic drug for type 2 diabetes, has been shown to have antiaging effects. However, the mechanisms of metformin in antiaging treatment remain controversial. Here, we used D-galactose (D-gal) to establish an appropriate model of senescent hBMSCs to explore the antiaging effects of metformin...

In the oral and maxillofacial region, the treatment of severe bone defects, caused by fractures, cancers, congenital abnormalities, etc., remains a great challenge. In addition, neurological disorders are frequently accompanied by these bone defects or the treatments for them. Therefore, novel bone regenerative techniques and methods to repair nerve injury are eagerly sought. Among them, strategies using dental pulp stem cells (DPSCs) are promising options. Human DPSCs can be collected easily from extracted teeth and are now considered a type of mesenchymal stem cell with higher clonogenic and proliferative potential...

The fertility of females of childbearing age who are cured of cancer by chemotherapy is gradually declining globally. As a broad-spectrum chemotherapy drug in clinic, the damage of cisplatin (CDDP) to female reproductive function cannot be ignored. At present, the study of CDDP damage to the uterus is not sufficient, and the exact mechanism needs to be further explored. Therefore, we conducted this research to determine whether uterine injury in CDDP-induced injury rats might be improved by human umbilical cord mesenchymal stem cells (hUMSCs) and to further explore the precise mechanism...

Bone fracture repair is a multiphased regenerative process requiring paracrine intervention throughout the healing process. Mesenchymal stem cells (MSCs) play a crucial role in cell-to-cell communication and the regeneration of tissue, but their transplantation is difficult to regulate. The paracrine processes that occur in MSC-derived extracellular vesicles (MSC-EVs) have been exploited for this study. The primary goal was to determine whether EVs secreted by TGF- β 1-stimulated MSCs (MSCTGF- β 1 -EVs) exhibit greater effects on bone fracture healing than EVs secreted by PBS-treated MSCs (MSCPBS -EVs)...

Tendons are associated with a high injury risk because of their overuse and age-related tissue degeneration. Thus, tendon injuries pose great clinical and economic challenges to the society. Unfortunately, the natural healing capacity of tendons is far from perfect, and they respond poorly to conventional treatments when injured. Consequently, tendons require a long period of healing and recovery, and the initial strength and function of a repaired tendon cannot be completely restored as it is prone to a high rate of rerupture...

Overactive inflammatory responses contribute to progressive cardiac dysfunction after myocardial infarction (MI). Mesenchymal stem cell (MSC) has generated significant interest as potent immune modulators that can regulate excessive immune responses. We hypothesized that intravenous (iv) administration of human umbilical cord-derived MSC (HucMSC) exerts systemic and local anti-inflammation effects, leading to improved heart function after MI. In murine MI models, we confirmed that single iv administration of HucMSC (30 × 104 ) improved cardiac performance and prevented adverse remodeling after MI...

Intestinal epithelial dysfunction is critical in the development of inflammatory bowel disease (IBD). However, most cellular experiments related to epithelial barrier studies in IBD have been based on tumor cell line that lack a variety of intestinal epithelial cell types. Thus, intestinal organoids can present the three-dimensional structure and better simulate the physiological structure and function of the intestinal epithelium in vitro . Here, the crypts were isolated from the small intestine of mice; with the participation of major cytokines (EGF, Noggin, and R-Spondin 1 included), the intestinal organoids were established at a density of 100 crypts per well, containing intestinal stem cells (ISC), Paneth cells, goblet cells, and intestinal endocrine cells...

METHODS: Electronic searches were conducted in five databases including CENTRAL, MEDLINE, EMBASE, Web of Science, and Dentistry & Oral Sciences Source using a combination of MeSH terms and keywords up to 21 June 2022. Human studies including patients aged over 18 years with all forms of periodontitis were included. Following the risk of bias assessment, both qualitative and quantitative analyses were performed. RESULTS: A total of twelve studies were included in qualitative analysis and six of them in quantitative analyses...

Periodontal ligament stem cells (PDLSCs) are considered ideal cell sources for the regeneration of periodontal and alveolar bone tissue. Cytoskeleton Regulator RNA ( CYTOR ), a newly discovered long noncoding RNA, has been reported to function as competing endogenous RNA (ceRNA) and to be involved in many biological processes. However, its roles in PDLSC osteogenic differentiation remain unclear. Here, we firstly found CYTOR was mainly sublocalized in the cytoplasm of PDLSCs and CYTOR expression was increased during osteogenic differentiation of PDLSCs...

BACKGROUND: Necroptosis is progressively becoming an important focus of research because of its role in the pathogenesis of cancer and other inflammatory diseases. Our study is designed to anticipate the survival time of kidney renal clear cell carcinoma (KIRC) by constructing a prognostic signature of necroptosis-related genes. MATERIALS: Clinical information and RNA-seq data were acquired from Renal Cell Cancer-European Union (RECA-EU) and The Cancer Genome Atlas- (TCGA-) KIRC, respectively...

BACKGROUND: Colorectal cancer (CRC) is one of the commonest cancers worldwide. As conventional biomarkers cannot clearly define the heterogeneity of CRC, it is essential to establish novel prognostic models. METHODS: For the training set, data pertaining to mutations, gene expression profiles, and clinical parameters were obtained from the Cancer Genome Atlas. Consensus clustering analysis was used to identify the CRC immune subtypes. CIBERSORT was used to analyze the immune heterogeneity across different CRC subgroups...

Blood-brain barrier (BBB) is the most important component of central nervous system (CNS) to keep toxins and pathogens from CNS. Although our studies demonstrated that using interleukin-6 antibodies (IL-6-AB) reversed the increased permeability of BBB, IL-6-AB is limited in their application that only could be used a few hours before surgery and seemed delayed the surgical wounds healing process, which urges us to find another more effective method. In this study, we employed the C57BL/6J female mice to investigate the potential effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) transplantation on BBB dysfunction induced by surgical wound...

Human menstrual blood-derived mesenchymal stem cells (MenSCs) and their secreted small extracellular vesicles (EVs) had been proven to relieve inflammation, tissue damage, and fibrosis in various organs. The microenvironment induced by inflammatory cytokines can promote mesenchymal stem cells (MSCs) to secrete more substances (including EVs) that could regulate inflammation. Inflammatory bowel disease (IBD) is a chronic idiopathic intestinal inflammation, the etiology and mechanism of which are unclear. At present, the existing therapeutic methods are ineffective for many patients and have obvious side effects...

It is unclear whether extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) have a direct protective effect on pancreatic islets. In addition, whether culturing MSCs in three dimensions (3D) instead of a monolayer (2D) can induce changes in the cargo of EVs that facilitate the polarization of macrophages into an M2 phenotype has not been investigated. We sought to determine whether EVs from MSCs cultured in 3D can prevent inflammation and dedifferentiation in pancreatic islets and, if so, whether the protective effect is superior to that of EVs from 2D MSCs...