Journal of Stem Cell Research & Therapy

One reason for lack of efficacy in cancer therapeutics is tumor heterogeneity. We hypothesize that tumor heterogeneity arises due to emergence of multiple Cancer Stem Cell (CSC) subpopulations because miRNAs regulate expression of stem cell genes in CSCs. Our goal was to determine if: i) multiple CSC subpopulations exist in a human CRC cell population, and ii) miRNAs are differentially expressed in the different CSC subpopulations. We discovered that at least four different CSC populations (ALDH1, CD166, LGR5, and LRIG1) exist in the HT29 cell line...

Background: Colorectal Cancer (CRC) is the third most common cancer diagnosed and the second leading cause of cancer-related deaths in the United States. Cancer Stem Cells (CSCs) are believed to be the primary reason for the recurrence of CRC. Specific stem cell marker, doublecortin-like kinase 1 (DCLK1) plays critical roles in the tumorigenesis and progression of CRC. Up-regulation of DCLK1 is correlated with poor prognosis. Whether DCLK1 is correlated with enhanced chemoresistance of CRC cells is unclear...

Mitochondria are vital organelles that supply ATP and other energy metabolites to meet the bioenergetics demands of the cell. In environments of stress or increased energy requirement, mitochondria are highly dynamic and can undergo biogenesis, fusion/fission, or autophagy. The transcription factor family, Kruppel-Like Factor (KLF), is necessary to carry out normal cellular processes from proliferation to differentiation. Recently, its importance in metabolic homeostasis in various tissue types has gained much attention...

The cerebellum, a derivative of the hindbrain, plays a crucial role in balance and posture as well as in higher cognitive and locomotive processes. Cerebellar development is initiated during the segmental phase of hindbrain formation. Here, we describe the phenotype, of a single surviving adult conditional mouse mutant mouse, in which Sox2 function is ablated in embryonic radial glial cells by means of hGFAP-CRE. The single Sox2RGINV/mosaic adult mutant mouse displays motor disability, microsomia, reduced Central Nervous System (CNS) size and cerebellar defects associated with human genetically related congenital abnormalities...

Objective: Resident cardiac stem cells are expected to be a therapeutic option for patients who suffer from severe heart failure. However, uncertainty remains over whether sorting cells for c-kit, a stem cell marker, improves therapeutic outcomes. Materials and methods: Cardiac outgrowth cells cultured from explants of rat heart atrium were sorted according to their positivity (+) or negativity (-) for c-kit. These cells were exposed to hypoxia for 3 d, and subsequently harvested for mRNA expression measurement...

Dopamine (DA) is a well-known neurotransmitter and critical element in the mussel adhesive protein that has gained increasing attention for its role in cellular growth enhancement in biomaterials, including cellular adhesion improvement. As the mechanism underlying this remains unclear, the objective of this study was to explore the effects of DA on the adhesion properties of bone marrow derived rat mesenchymal stem cells (rMSCs) using an hydroxyapatite gelatin nanocomposite biomaterial and to test whether the effects are mediated through various endogenously expressed DA receptors...

Human Mesenchymal stem cells (hMSCs) secrete products (supernatants) that are anti-inflammatory and antimicrobial. We have previously shown that hMSCs decrease inflammation and Pseudomonas aeruginosa infection in the in vivo murine model of Cystic Fibrosis (CF). Cystic Fibrosis (CF) is a genetic disease in which pulmonary infection and inflammation becomes the major cause of morbidity and mortality. Our studies focus on determining how MSCs contribute to improved outcomes in the CF mouse model centering on how the MSCs impact the inflammatory response to pathogenic organisms...

Stem cell-based neuronal differentiation has provided a unique opportunity for disease modeling and regenerative medicine. We have reported a novel culture condition and method for generating neuronal progenitors and neural networks from human embryonic and induced pluripotent stem cells without any genetic manipulation. Neurospheres generated under 10% CO2 with Supplemented Knockout Serum Replacement Medium (SKSRM) had doubled the expression of NESTIN, PAX6 and FOXG1 genes compared to the neurospheres generated under 5% CO2 ...

BACKGROUND: Critical Limb Ischemia (CLI) affects patients with Type 2 Diabetes (T2D) and obesity, with high risk of amputation and post-surgical mortality, and no effective medical treatment. Stem cell therapy, mainly with bone marrow mesenchymal, adipose derived, endothelial, hematopoietic, and umbilical cord stem cells, is promising in CLI mouse and rat models and is in clinical trials. Their general focus is on angiogenic repair, with no reports on the alleviation of necrosis, lipofibrosis, and myofiber regeneration in the ischemic muscle, or the use of Muscle Derived Stem Cells (MDSC) alone or in combination with pharmacological adjuvants, in the context of CLI in T2D...

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Cancer handles an estimated 7.6 million deaths worldwide per annum. A recent theory focuses on the role Cancer Stem Cells (CSCs) in driving tumorigenesis and disease progression. This theory hypothesizes that a population of the tumor cell with similar functional and phenotypic characteristics as normal tissue stem cells are responsible for formation and advancement of many human cancers. The CSCs subpopulation can differentiate into non-CSC tumor cells and promote phenotypic and functional heterogeneity within the tumor...

RNA polymerase II (Pol II) temporarily stops transcription after synthesizing 30-50 bases, and resumes elongation only after stimulations by various signaling molecules and developmental cues. This phenomenon, called promoter-proximal pausing, is observed in 10-50% of the entire genes from Drosophila embryos to human cells. Release of paused Pol II is primarily mediated by the activated form of positive transcription elongation factor b (P-TEFb) initially sequestered in the inhibitory 7SK small nuclear ribonucleoprotein (7SK snRNP) complex...

BACKGROUND: Duchenne Muscular Dystrophy (DMD) is a recessive form of muscular disorder, resulting from the dystrophin gene mutations in X-chromosome. Application of embryonic stem cells or adult stem cells has demonstrated the therapeutic effects on DMD through both cell-based and non-cell based mechanisms. In this study, we proposed that Myogenic Progenitor Cells from Induced Pluripotent Stem Cells (iPSC-MPCs) would be more effective in repairing muscle damage caused by muscular dystrophy...

Disparities in clinical care have been described for patients with limited insurance coverage or social support. We hypothesized that patients with relapsed Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM) treated at an urban county hospital serving indigent and under-insured patients would face barriers for referral to a private academic transplant center for autologous stem cell transplantation (ASCT). Charts of patients with HL, NHL, or MM treated at Grady Memorial Hospital between 2007 and 2013 were reviewed, and 215 patients with diagnosis of HD (n=40), NHL (n=96), and MM (n=79)...

Characterizing subpopulations of stem cells is important to understand stem cell properties. Tissue-nonspecific alkaline phosphatase (ALP) is associated with mineral tissue forming cells as well as stem cells. Information regarding ALP subpopulation of human periodontal ligament stem cells (hPDLSCs) is limited. In the present study, we examined ALP+ and ALP- hPDLSC subpopulations, their surface markers STRO-1 and CD146, and the expression of stemness genes at various cell passages. We found that ALP+ subpopulation had higher levels of STRO-1 (30...

Apoptosis is one of the major factors contributing to the failure of human islet transplantation. Contributors to islet apoptosis exist in both the pre-transplantation and post transplantation stages. Factors include the islet isolation process, deterioration in vitro prior to transplantation, and immune rejection post transplantation. Previous studies have demonstrated that co-cultured bone marrow cells with human islets not only significantly enhanced the longevity of human islets but also maintained function...

Cell therapy represents a promising new paradigm for treatment of heart disease, a major cause of death in the industrialized world. The recent discovery of tissue resident c-Kit+ cardiac progenitor cells (CPCs) has fueled scientific efforts to exploit these cells therapeutically for regenerative interventions, and primary culture of cardiomyocytes is a common in-vitro model to investigate basic molecular mechanisms underlying cardiac degeneration and regeneration. Current protocols for cardiomyocyte isolation frequently result in low cell yield and insufficient depletion of fibroblasts, which then overgrow the cardiomyocytes in culture...

OBJECTIVE: To elucidate the role of oxidation resistance 1 (OXR1) gene. Oxidative stress plays a pivotal role in pathogenesis of immune-mediated nephritis. Recently we identified oxidation resistance 1 (OXR1) is conventionally expressed in eukaryotes and has an ability to prevent oxidative damage caused by various oxidative stresses. However the protective effect of OXR1 in immune-associated inflammatory response and oxidative damage is not clear and will be investigated in this study...

The clinical application of Mesenchymal Stem Cells (MSCs) for the treatment of a variety of diseases is the focus of intense research. Despite large research efforts many questions regarding MSC biology in vivo remain unanswered. For instance, we do not know for certain whether MSCs exert their therapeutic effects directly within the target tissue or indirectly by influencing the polarization of other cell types, such as macrophages, which can then home to the target tissue microenvironment. To help address this issue, the application of intravital multiphoton microscopy allows for the determination of the dynamic action of intact MSCs versus endogenous host cells at the target tissue site in real time...

Vitamin C is an essential micronutrient in the human diet; its deficiency leads to a number of symptoms and ultimately death. After entry into cells within the central nervous system (CNS) through sodium vitamin C transporters (SVCTs) and facilitative glucose transporters (GLUTs), vitamin C functions as a neuromodulator, enzymatic cofactor, and reactive oxygen species (ROS) scavenger; it also stimulates differentiation. In this review, we will compare the molecular and structural aspects of vitamin C and glucose transporters and their expression in endothelial or choroid plexus cells, which form part of the blood-brain barrier and blood-cerebrospinal fluid (CSF) barrier, respectively...