In recent years the concept of a stem cell has evolved to encompass the hypotheses that stem cells exist within many adult tissues, and that a common 'interchangeable' progenitor cell may exist within the bone marrow capable of regenerating and repairing tissues throughout the body. As more knowledge is gained about stem cells, their potential roles in disease processes, including the development and progression of cancer, have moved to the forefront. The underlying hypothesis of this review is that cell fate is determined by a combination of intrinsic and extrinsic factors; growth and differentiation are regulated through intracellular integration of a multitude of signals initiated by internal and external stimuli. The development of successful stem cell based therapies may depend on experimental approaches that consider both the intrinsic and extrinsic factors that control cell fate.
"Recent studies on tissue engineering techniques have introduced mesenchymal stem cells as a basic tool for the construction of bone tissue. A Mesenchymal stem cell is defined as a multipotent cell with indefinite self-renewal capability that can differentiate into a variety of cell types, including: Osteoblasts, chondrocytes, and adipocytes. Mesenchymal stem cells can be acquired from different tissues such as bone marrow, fat, bone, and dental pulp. "
[Show abstract][Hide abstract] ABSTRACT: There are significant limitations in repair of irrecoverable bone defects. Stem-cell therapy is a promising approach for the construction of bone tissue. Mesenchymal stem cells (MSCs) have been introduced as basic tools for bone tissue generation. Through MSCs, adipose-derived stem cells (ADSCs) are more interesting. Since the similarity of native osteoblasts and differentiated osteoblasts from ADSCs in terms of gene expression pattern is unknown, this study was designed to compare gene expression patterns of some genes involved in osteogenesis between human native osteoblasts and adipose-derived differentiated osteoblasts.
Realtime qRT-PCR was used for studying the gene expression of osteocalcin, osteopontin, and core binding factor alpha 1 (Cbfa1) in human native osteoblasts and adipose derived osteogenic osteoblasts at days 7, 14, 21, and 28 of differentiation.
This study demonstrated that native osteoblasts and differentiated osteoblasts, cultured in common osteogenic medium, have significant differences in gene expression levels for osteocalcin and osteopontin. Compared to native osteoblasts, these genes are expressed lower in all four groups of differentiated osteoblastic cells. We also found, there is a progressive increase in cbfa1 expression over the differentiation period of ADSCs from day 7 to day 28.
Our findings help for better assessment of adipose-derived differentiated cells as a source for cell-based therapy.
"It is widely accepted that adult stem cells are involved in normal tissue replenishment throughout life while cancer stem cells support cancer growth (Presnell et al., 2002, Smith et al., 2007). Although the cell(s) of origin for prostate cancer may include luminal, basal, neuroendocrine, progenitor and stem cells (Kasper, 2008, Wang et al., 2009), it is increasingly evident that the resultant prostate cancers contain cancer stem cells that continuously seed and maintain tumor growth (Gu et al., 2007, Kasper, 2008, Kasper, 2009). "
[Show abstract][Hide abstract] ABSTRACT: Estrogen reprogramming of the prostate gland as a function of developmental exposures (aka developmental estrogenization) results in permanent alterations in structure and gene expression that lead to an increased incidence of prostatic lesions with aging. Endocrine disrupting chemicals (EDCs) with estrogenic activity have been similarly linked to an increased prostate cancer risk. Since it has been suggested that stem cells and cancer stem cells are potential targets of cancer initiation and disease management, it is highly possible that estrogens and EDCs influence the development and progression of prostate cancer through reprogramming and transforming the prostate stem and early stage progenitor cells. In this article, we review recent literature highlighting the effects of estrogens and EDCs on prostate cancer risk and discuss recent advances in prostate stem/progenitor cell research. Our laboratory has recently developed a novel prostasphere model using normal human prostate stem/progenitor cells and established that these cells express estrogen receptors (ERs) and are direct targets of estrogen action. Further, using a chimeric in vivo prostate model derived from these normal human prostate progenitor cells, we demonstrated for the first time that estrogens initiate and promote prostatic carcinogenesis in an androgen-supported environment. We herein discuss these findings and highlight new evidence using our in vitro human prostasphere assay for perturbations in human prostate stem cell self-renewal and differentiation by natural steroids as well as EDCs. These findings support the hypothesis that tissue stem cells may be direct EDC targets which may underlie life-long reprogramming as a consequence of developmental and/or transient adult exposures.
"The existence of cancer stem cells (CSCs) was first demonstrated by transplantation of a small population of harvested leukaemia cells from patients into immunedeficient mice, which then developed the same cancer (Bonnet and Dick, 1997). Since then, recent evidence suggests that a subset of cells within a tumour has stem-like characteristics, including the ability to initiate tumours, high proliferative rates, a high capacity of self-renewal, and the propensity to differentiate into actively proliferating tumour cells (Reya et al, 2001; Presnell et al, 2002; Pardal et al, 2003). These stem-like tumour cells are often associated with elevated expression of the stem cell surface marker CD133 (Neuzil et al, 2007). "
[Show abstract][Hide abstract] ABSTRACT: Although CD133 has been shown to be a marker for cancer stem cells in various tumours, its expression in pancreatic cancer has not yet been clinically reported. In this study, we investigated the relationship between CD133 expression and clinicopathological factors in pancreatic cancer. Pancreatic head carcinoma specimens from 80 patients who underwent surgical resection were immunohistochemically assessed for CD133, vascular endothelial growth factor (VEGF)-C, CXCR4, CD34, Ki-67, and cytokeratin (CK) expressions. Sixty percentage (48/80) of specimens were CD133-positive, with less than 15% cells per specimen expressing the marker. CD133-positive cells were found at the peripheral site of adenocarcinoma glandular structures and were negative for CK. There was a significant correlation between CD133 expression and clinicopathological factors, including histological type, lymphatic invasion, and lymph node metastasis (P=0.0215, 0.0023, and 0.0024, respectively). Vascular endothelial growth factor-C expression was also significantly correlated with CD133 expression (P=0.0002). Consequently, the 5-year survival rate of CD133-positive patients was significantly lower than that of CD133-negative patients (P=0.0002) and multivariate analysis revealed that CD133 expression was an independent prognostic factor (P=0.0103). These results suggest that CD133 expression in pancreatic cancer was significantly associated with lymphatic metastasis, VEGF-C expression, and prognosis.
British Journal of Cancer 05/2008; 98(8):1389-97. DOI:10.1038/sj.bjc.6604307 · 4.84 Impact Factor
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