Paula Ferraces-RiegasAnona C. GalbraithDavid P. Doupé
12页
查看更多>>摘要：Epithelial stem cells maintain tissues throughout adult life and are tightly regulated by their microenvironmental niche to balance cell production and loss. These stem cells have been studied extensively as signal-receiving cells, responding to cues from other cell types and mechanical stimuli that comprise the niche. However, studies from a wide range of systems have identified epithelial stem cells as major contributors to their own microenvironment either through producing niche cells, acting directly as niche cells or regulating niche cells. The importance of stem cell contributions to the niche is particularly clear in cancer, where tumour cells extensively remodel their microenvironment to promote their survival and proliferation.
查看更多>>摘要：In this next volume in the Cell Biology and Translational Medicine series, we continue to explore fundamentals of stem cell biology as well as their potential utility in regenerative medicine applications. Amongst topics explored in this volume are recent advances in understanding of the epithelial stem cell niche, identifying small molecules for stem cell expansion in vitro, and recent developments in cell therapy, in particular islet cell transplant for treatment of diabetes. A major objective of the series continues to be to highlight timely, often emerging topics and novel approaches that can accelerate realizing the utility of stem cells in regenerative medicine. Amongst the latter is the use of zebrafish as a platform to screen drugs that regulate stem cell function. I remain very grateful to Gonzalo Cordova, the associate editor of the series, and wish to acknowledge his continued support. I would also like to acknowledge and thank Mariska van der Stigchel, Assistant Editor, for her outstanding efforts in helping to bring this volume to the production stages. A special thank you goes to Shanthi Ramamoorthy and Rathika Ramkumar for their outstanding efforts in the production of this volume.
查看更多>>摘要：Parathyroid glands are endocrine organs which are located posterior to thyroid glands and control secretion of parathyroid hormone (PTH) in order to regulate blood calcium level. PTH maintains calcium homeostasis by acting on the bone, kidney, and small intestine. PTH deficiency leads to chronic hypocalcemia, organ calcinosis, kidney and heart failure, painful muscle spasms, neuromuscular problems, and memory problems. Since parathyroid cells have inadequate proliferation potential in culture conditions, their utilization as a cellular therapy option is very limited. Although studies conducted so far include parathyroid cell differentiation from various cell types, problems related to successful cellular differentiation and transplantation still remain. Recently, parathyroid tissue engineering has attracted attention as a potential treatment for the parathyroid-related diseases caused by hypoparathyroidism. Although major progression is made in the construction of tissue engineering protocols using parathyroid cells and biomaterials, PTH secretion to mimic its spontaneous harmony in the body is a challenge. This chapter comprehensively defines the derivation of parathyroid cells from various cell sources including pluripotent stem cells, molecular mechanisms, and tissue engineering applications.
查看更多>>摘要：Mesenchymal stem cell (MSC) has recently generated interest in regenerative medicine. For the definition of MSC, three criteria have been proposed - plastic adherent property, specific surface antigens, and multipotent differentiation capacity. MSC exists in almost all tissues such as synovium, fat, liver, dental pulp, cord blood, Wharton’s jelly, and also differentiates into osteoblast, chondrocyte, adipocyte, epithelial, and neuron cells originating from three germ layers. The use of different MSCs for regenerative therapies has been studied over the years as a promising option for treatment of tissue damages and various diseases. Here, the most frequently applied and newly developed stem cell-based techniques are designated, and recent MSC applications knowledge for regenerative medicine in the field are explained.
查看更多>>摘要：Mesenchymal stem cells (MSCs) have been shown to be promising for regenerative medicines with their immunomodulatory characteristics. They may be obtained from a variety of tissue types, including umbilical cord, adipose tissue, dental tissue, and bone marrow (BM). BM-MSCs are challenging in terms of their ex vivo expansion capability. Thus, we aimed to improve the expansion of BM-MSCs with small molecule treatments. We tested about forty small molecules that are potent quiescence modulators, and determined their efficacy by analysis of cell viability, cell cycle, and apoptosis in BM-MSCs. We also examined gene expression for selected small molecules to explore essential molecular pathways. We observed that treatment with SB203580 increased BM-MSCs expansion up to two fold when used for 5 days. SB203580 decreased the proportion of cells in the G1 phase of the cell cycle and substantially increased the ratio of cells in the S-G2-M phase. Enhanced MSC expansion with SB203580 therapy was associated with the lower expression of CDKIs like p15, p18, p19, p21, p27, and p57. In conclusion, we have developed a new approach to facilitate the expansion of BM-MSCs. These results could enhance autologous and immunomodulation therapy involving BM-MSCs.
查看更多>>摘要：The prevalence of neurodegenerative diseases is steadily increasing worldwide, and epidemiological studies strongly suggest that many of the diseases are sex-biased. It has long been suggested that biological sex differences are crucial for neurodegenerative diseases; however, how biological sex affects disease initiation, progression, and severity is not well-understood. Sex is a critical biological variable that should be taken into account in basic research, and this review aims to highlight the utility of human-induced pluripotent stem cells (iPSC)-derived models for studying sex-specific differences in neurodegenerative diseases, with advantages and limitations. In vitro systems utilizing speciesspecific, renewable, and physiologically relevant cell sources can provide powerful platforms for mechanistic studies, toxicity testings, and drug discovery. Matched healthy, patient-derived, and gene-corrected human iPSCs, from both sexes, can be utilized to generate neuronal and glial cell types affected by specific neurodegenerative diseases to study sex-specific differences in two-dimensional (2D) and three-dimensional (3D) human culture systems. Such relatively simple and well-controlled systems can significantly contribute to the elucidation of molecular mechanisms underlying sex-specific differences, which can yield effective, and potentially sex-based strategies, against neurodegenerative diseases.
Kevin VerhoeffBraulio A. Marfil-GarzaNerea Cuesta-GomezIla Jasra...
18页
查看更多>>摘要：Islet cell transplant (ITx) continues to improve, with recently published long-term outcomes suggesting nearly 80% graft survival, leading to improvements in glycemic control, reductions in insulin doses, and near-complete abrogation of severe hypoglycemia. Unfortunately, access to ITx remains limited by immunosuppression requirements and donor supply. Discovery of stem cell-derived functional islet-like clusters with the capacity to reverse diabetes offers a renewable, potentially immunosuppression-free solution for future widespread ITx. Evaluation and optimization of these therapies is ongoing, but may one day provide a realistic cure for type 1 diabetes. However, stem cellbased ITx has unique immunologic questions that remain unanswered. Here, we briefly synthesize current approaches for stem cell-derived ITx, review humanized mice models, and elaborate on the potential of humanized mice models for bridging the gap between current small rodent models and human clinical trials for allogeneic and autologous inducible pluripotent stem cell (iPSC)-based ITx while highlighting limitations and future directions.
查看更多>>摘要：Osteoarthritis (OA) is a common progressively degenerative joint disease that affects more than 300 million people worldwide. OA is manifested by articular cartilage degradation, chronic pain, deformity, functional disability, and decreased quality of life. A real challenge in OA management is the lack of an effective cure because exiting therapeutics often provide symptom control rather than disease modification; therefore, they fail to prevent disease progression. The inadequate treatments for OA management have encouraged researchers to study mesenchymal stem cells (MSCs) as an investigational treatment for OA. MSCs are a promising tool for OA because of their availability; expand cultivation and multi-lineage differentiation capacity as well as well-documented paracrine function have made MSCs a promising tool in this field. Accordingly, MSCs application has been successfully utilized in a broad range of pre-clinical OA animal models as well as clinical studies with the aim of cartilage repair which had not previously been achieved using classical treatments. Here, the brief scientific review of MSC role in the control of OA as well as the proposed mechanisms are discussed. We provide an insight into the last 10 years’ studies conducted on preclinical and clinical OA treatment as well as future opportunities in OA management strategies employing MSCs.
查看更多>>摘要：Acute leukemia (AL) is a poor progressive resistant hematological disease, which has different subtypes and immunophenotypic properties according to leukemic blasts. AL is caused by genetic changes and associated with leukemia stem cells (LSCs), which determine its prognosis and endurance. LSCs are thought to be hematopoietic progenitor and stem cell (HPSCs)-like cells that underwent a malignant transformation. In addition to their low number, LSCs have the characteristics of self-renewal, resistance to chemotherapy, and relapse of leukemia. The myeloid ecotropic integration site-1 (MEIS1) protein is a member of the three-amino acid loop extension (TALE) family of homeodomain (HD) proteins that can bind to DNA sequence-specific manner. Studies have shown that overexpression of MEIS1 and associated cofactors involves tumorigenesis of numerous cancers. Historically, increased expression of Meisl transcript as well as protein has been determined in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients. Moreover, resistance to conventional chemotherapy was observed in leukemic blast samples with high Meisl content. In this review article, the molecular mechanism of the oncological role of the MEIS1 protein in leukemia and LSC is discussed. In addition, it was suggested that MEIS1 protein could be utilized as a possible treatment target in leukemia with an emphasis on the inhibition of MEIS1, which is overexpressed in LSC.
查看更多>>摘要：Animal studies are recognized as a significant step forward in the bridging between drug discovery and clinical applications. Animal models, due to their relative genetic, molecular, physiological, and even anatomical similarities to humans, can provide a suitable platform for unraveling the mechanisms underlying human diseases and discovering new therapeutic approaches as well. Recently, zebrafish has attracted attention as a valuable experimental and pharmacological model in drug discovery and development studies due to its prominent characteristics such as the high degree of genetic similarity with humans, genetic manipulability, and prominent clinical features. Since advancing a theory to a valid and reliable observation requires the manipulation of animals, it is, therefore, essential to use efficient modeling methods appropriate to the different aspects of experimental conditions. In this context, applying several various approaches such as using chemicals, pathogens, and genetic manipulation approaches allows zebrafish development into a preferable model that mimics some human disease pathophysiology. Thus, such modeling approaches not only can provide a framework for a comprehensive understanding of the human disease mechanisms that have a counterpart in zebrafish but also can pave the way for discovering new drugs that are accompanied by higher amelioration effects on different human diseases.
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