Stem cell

The development of new drugs for musculoskeletal regeneration purposes has attracted much attention in the last decades. In this work, we present three novel vitamin B9 (folic acid)-derivatives bearing divalent cations (ZnFO, MgFO and MnFO), providing their synthesis mechanism and physicochemical characterization. In addition, a strong emphasis has been placed on evaluating their biological properties (along with our previously reported SrFO) using human mesenchymal stem cells (hMSC). In all the cases, pure folate derivatives (MFOs) with a bidentate coordination mode between the metal and the folate anion, and a 1:1 stoichiometry, were obtained in high yields...

Hypertrophic cardiomyopathy (HCM) is a heterogeneous myocardial disease often caused by sarcomeric gene mutations. MYH7 is one of the most common genes associated with HCM. In this study, we generated a human induced pluripotent stem cell (iPSC) line ZZUNEUi020-A from peripheral blood mononuclear cells of a female HCM patient with the p. R719Q (c. 2156G > A) mutation in MYH7. This cell line expressed pluripotency markers, showed normal female karyotype and could differentiate into all three germ layers in vitro...

X-linked agammaglobulinemia (XLA, OMIM #300755) is one of the most common pediatric primary immunodeficiencies characterized by failure to produce mature B lymphocytes and hypogammaglobulinemia, caused by mutation of the gene encoding Bruton's tyrosine kinase (BTK, OMIM *300300), a key regulator in B-cell development. Patientssuffering XLA are prone to recurrentbacterial infection. We established an induced pluripotent stem cells (iPSCs) line from a 3-year-5-month-old boy with XLA caused by a hemizygous in-frame 9-bp deletion in BTK (c...

We previously reported the efficient targeted introduction of transgenes into the genomic DNA of the common marmoset (Callithrix jacchus) using CRISPR-Cas9. In this study, we generated a marmoset embryonic stem cell (ESC) line that ubiquitously expresses the tamoxifen-inducible Cre-driver ERT2CreERT2. We validated the pluripotency of the ESC line and also successfully demonstrated the temporal control of the Cre-driver in a tamoxifen-dependent manner in the ESCs. This ESC line, named ActiCre-B1, will be a valuable resource for in vitro investigation of phenotypes related to embryonic lethality by targeted knockout of functionally important genes...

BACKGROUND: There is an unmet need to identify biomarkers that directly reflect response to adjuvant radiotherapy (RT). Circulating epithelial tumor cells (CETCs) represent the liquid component of solid tumors and are responsible for metastatic relapse. CETC subsets with cancer stem cell characteristics, circulating cancer stem cells (cCSCs), play a pivotal role in the metastatic cascade. Monitoring the most aggressive subpopulation of CETCs could reflect the aggressiveness of the remaining tumor burden...

The adverse effects of glucocorticoids (GCs) on bone marrow stromal stem cells (BMSCs) play an important role in steroid-induced osteonecrosis of the femoral head (ONFH). Our previous miRNA microarray analysis indicated that microRNA-224-5p (miR-224-5p) could be a potential regulator; however, the underlying mechanism remains unclear. In the present study, we demonstrated that miR-224-5p was upregulated in GC-treated BMSCs, and functional experiments revealed that miR-224-5p could suppress osteogenic but promote adipogenic differentiation of BMSCs...

The insulin and insulin-like growth factor-1 (IGF-1) receptors are important for the growth and development of embryonic tissues. To directly define their roles in the maintenance of pluripotency and differentiation of stem cells, we knocked out both the receptors in induced pluripotent stem cells (iPSCs). iPSCs lacking both the insulin and IGF-1 receptors (double knock-out, DKO) exhibited preserved pluripotency potential despite decreased expression of the transcription factors, Lin28a and Tbx3, compared to control iPSCs...

The existing approaches for healing mandibular condylar osteochondral defects, which are prevalent in temporomandibular joint disorders (TMD), are sparse and not reparative. To address this, regenerative medicine in situ has transpired as a potential therapeutic solution as it can effectively regenerate composite tissues. Herein, injectable self-crosslinking thiolated hyaluronic acid (HA-SH)/type I collagen (Col I) blend hydrogel and BCP ceramics combined with rabbit bone mesenchymal stem cells (rBMSCs)/chondrocytes were used to fabricate a new bi-layer scaffold to simulate specific structure of rabbit condylar osteochondral defects...

Glioblastoma (GBM) and other malignant tumours consist of heterogeneous cancer cells, including GBM-initiating cells (GICs). This heterogeneity is likely to arise from the following: different sets of genetic mutations and epigenetic modifications, which GICs gain in the transformation process; differences in cells of origin, such as stem cells, precursor cells or differentiated cells; and the cancer microenvironment, in which GICs communicate with neural cells, endothelial cells and immune cells. Furthermore, considering that various types of GICs can be generated at different time points of the transformation process, GBM very likely consists of heterogeneous GICs and their progeny...

BAALC is identified as a leukemia-associated gene and is highly expressed in CD34 positive hematopoietic stem cells. High BAALC expression is associated with poor prognosis in several types of acute myeloid leukemia. We explored binding partner proteins of BAALC by means of mass spectrometry and analyzed biological properties of BAALC expressing leukemic cells. We revealed that BAALC physically interacts with DBN1, which is an actin-binding protein and promotes cell adhesion and mobility by forming cell membrane spine during cell-cell interaction...

Adrenal insufficiency, the inability to produce adequate levels of corticosteroids, is a multi-causal disease that requires lifelong daily hormone replacement. Nevertheless, this cannot replace the physiological demand for steroids which are secreted following a circadian rhythm and vary in periods of stress; the consequences of under- or over-replacement include adrenal crisis and metabolic disturbances, respectively. Although clinical research has focused on enhancing the effectiveness/reducing side effects of current treatment modalities, only small improvements are deemed possible; thus, alternative solutions are urgently needed...

Sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide-dependent deacetylase, epigenetically regulates various cell metabolisms, including inflammation, tumorigenesis, and bone metabolism. Many clinical studies have found the potential of SIRT1 in predicting and treating bone-related disorders, such as osteoporosis and osteonecrosis, suggesting that SIRT1 might be a regulator of bone homeostasis. In order to identify the mechanisms that underlie the pivotal role of SIRT1 in bone homeostasis, many studies revealed that SIRT1 could maintain the balance between bone formation and absorption via regulating the ratio of osteoblasts to osteoclasts...

Cardiac fibroblasts and myofibroblasts assemble and maintain extracellular matrix during normal development and following injury. Culture expansion of these cells yield a bioengineered matrix that could lead to intriguing therapeutic opportunities. For example, we reported that cultured rat cardiac fibroblasts form a matrix that can be used to delivery therapeutic stem cells. Furthermore, we reported that matrix derived from cultured human cardiac fibroblasts/myofibroblasts converted monocytes into macrophages that express interesting anti-inflammatory and pro-angiogenic properties...

In order to fulfill cell proliferation and differentiation through cellular hierarchy, stem cells can undergo either asymmetric or symmetric divisions. Recent studies pay special attention to the effect of different modes of stem cell division on the lifetime risk of cancer, and report that symmetric division is more beneficial to delay the onset of cancer. The fate uncertainty of symmetric division is considered to be the reason for the cancer-delaying effect. In this paper we compare asymmetric and symmetric divisions of stem cells via studying stochastic stem cell models with mutation...

Human testis development in prenatal life involves complex changes in germline and somatic cell identity. To better understand, we profiled and analyzed ∼32,500 single-cell transcriptomes of testicular cells from embryonic, fetal, and infant stages. Our data show that at 6-7 weeks postfertilization, as the testicular cords are established, the Sertoli and interstitial cells originate from a common heterogeneous progenitor pool, which then resolves into fetal Sertoli cells (expressing tube-forming genes) or interstitial cells (including Leydig-lineage cells expressing steroidogenesis genes)...

BACKGROUND: A complete understanding of oral mucositis (OM) is crucial to develop appropriate interventions to aid in the successful overall health outcome of paediatric patients undergoing haematopoietic stem cell transplantation (HSCT). This study aimed at determining the prevalence and severity of OM, and at identifying the predictive factors that might aggravate OM at one-week, two-week, and three-week post-HSCT. METHODS: This retrospective, hospital-based study reviewed the medical records of 170 paediatric patients, summarising the patients' characteristics using descriptive statistics...

Perinatal hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal death and permanent neurological deficits. However, effective treatments have not yet been established, except therapeutic hypothermia, which is not effective for severe HIE. Therefore, developing a novel therapy for HIE is of the utmost importance. Stem cell therapy has been recently identified as a novel therapy for HIE. Among the various stem cell sources, ethical hurdles can be avoided using stem cells originating from non-embryonic or non-neural tissues such as umbilical cord blood cells (UCBCs), which are readily available and can be exploited for autologous transplantations...

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Dedifferentiation of cell identity to a progenitor-like or stem cell-like state with increased cellular plasticity is frequently observed in cancer formation. During this process, a subpopulation of cells in tumours acquires a stem cell-like state partially resembling to naturally occurring pluripotent stem cells that are temporarily present during early embryogenesis. Such characteristics allow these cancer stem cells (CSCs) to give rise to the whole tumour with its entire cellular heterogeneity and thereby support metastases formation while being resistant to current cancer therapeutics...

BACKGROUND: Patients with Ewing's sarcoma family of tumors (ESFT) who experience relapse or progression have a poor prognosis. AIM: This study aimed to identify the prognostic and therapeutic factors affecting overall survival (OS) of patients with recurrent or refractory localized ESFT. METHODS AND RESULTS: Thirty-eight patients with localized ESFT who experienced first relapse or progression between 2000 and 2018 were retrospectively reviewed...