Role of Hyperglycemia in the Senescence of Mesenchymal Stem Cells
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The regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) have laid a sound foundation for their clinical application in various diseases. However, the clinical efficiency of MSC treatments varies depending on certain cell characteristics. Among these, the roles of cell aging or senescence cannot be excluded. Despite their stemness, evidence of senescence in MSCs has recently gained attention. Many factors may contribute to the senescence of MSCs, including MSC origin (biological niche), donor conditions (age, obesity, diseases, or unknown factors), and culture conditions in vitro. With the rapidly increasing prevalence of diabetes mellitus (DM) and gestational diabetes mellitus (GDM), the effects of hyperglycemia on the senescence of MSCs should be evaluated to improve the application of autologous MSCs. This review aims to present the available data on the senescence of MSCs, its relationship with hyperglycemia, and the strategies to suppress the senescence of MSCs in a hyperglycemic environment.Keywords:
Senescence
Regenerative Medicine
To identify senescence‐associated genes (SAGs) in rice leaves, senescence was induced by transferring rice seedlings into darkness. Senescence up‐regulated cDNAs were obtained by PCR‐based subtractive hybridization. Among 14 SAG clones characterized, 11 were found to be associated with both dark‐induced and natural leaf senescence. Three clones were associated only with dark‐induced leaf senescence. The possible physiological roles of these SAGs during rice leaf senescence are discussed.
Senescence
Suppression subtractive hybridization
Cloning (programming)
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Cellular senescence is a complex process associated with irreversible cell cycle arrest. We can distinguish replicative senescence, which is telomere dependent and stress-induced premature senescence (SIPS), which is telomere independent. Replicative senescence can be observed in culture after a few weeks or months, depending on the cell type. On the other hand SIPS can be observed a few days after treating with a senescence inducing agent. Till now a universal marker of senescence has not been decribed. Studies concerning senescence are possible thanks to the existance of many markers of senescence which enable to observe molecular as well as biochemical changes associated with this process. The presence of a few markers of senescence allows us to be sure that cells underwent senescence.
Senescence
Cellular senescence
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Senescence
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Regenerative Medicine
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Regenerative medicine is a promising interdisciplinary field that applies basic principles of engineering and life sciences to repair, replace, or regenerate damaged or lost tissues and organs. Unlike conventional medicine, regenerative medicine uses human cells and other substances to regrow tissues or restore their functions. Regenerative medicine combines approaches such as the use of cell-based, cell-free soluble molecules, stem cells from different sources, gene therapy, tissue engineering, reprogramming of cells, and, more recently, cell-free regenerative therapies. Regenerative Medicine provides details of the recent advancements in regenerative therapies for regenerative medicine applications.
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In addition to age and developmental progress, leaf senescence and senescence-associated genes (SAGs) can be induced by other factors such as plant hormones, pathogen infection and environmental stresses. The relationship is not clear, however, between these induced senescence processes and developmental leaf senescence, and to what extent these senescence-promoting signals mimic age and developmental senescence in terms of gene expression profiles. By analysing microarray expression data from 27 different treatments (that are known to promote senescence) and comparing them with that from developmental leaf senescence, we were able to show that at early stages of treatments, different hormones and stresses showed limited similarity in the induction of gene expression to that of developmental leaf senescence. Once the senescence process is initiated, as evidenced by visible yellowing, generally after a prolonged period of treatments, a great proportion of SAGs of developmental leaf senescence are shared by gene expression profiles in response to different treatments. This indicates that although different signals that lead to initiation of senescence may do so through distinct signal transduction pathways, senescence processes induced either developmentally or by different senescence-promoting treatments may share common execution events.
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SUMMARY Leaf senescence is a hiphly‐controlled sequence of events comprising the final stage of development. Cells remain viable during the process and new gene expression is required. There is some similarity between senescence in plants and programmed cell death in animals. In this review, different classes of senescence‐related genes are defined and progress towards isolating such genes is reported. A range of internal and external factors which appear to cause leaf senescence is considered and various models for the mechanism of senescence‐ initiation are described. The current understanding of senescence at the wrganelle and molecular levels is presented. Finally, same ideas are mooted as to why senescence occurs and why it should be studied further. Contents Summary 419 I. Introduction 420 II. Internal factors that cause senescence 423 III. External factors that cause senescence 427 IV. What is the mechanism of senescence initiation? 428 V. Progress in the understanding of organelle senescence 431 VI. Progress in the understanding of senescence at the molecular level 434 VII. The control of senescence in animals and plants 440 VIII. Why is senescence necessary? 441 IX. Why study senescence? 441 References 442
Senescence
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Regenerative Medicine
Cell therapy
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The regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) have laid a sound foundation for their clinical application in various diseases. However, the clinical efficiency of MSC treatments varies depending on certain cell characteristics. Among these, the roles of cell aging or senescence cannot be excluded. Despite their stemness, evidence of senescence in MSCs has recently gained attention. Many factors may contribute to the senescence of MSCs, including MSC origin (biological niche), donor conditions (age, obesity, diseases, or unknown factors), and culture conditions in vitro. With the rapidly increasing prevalence of diabetes mellitus (DM) and gestational diabetes mellitus (GDM), the effects of hyperglycemia on the senescence of MSCs should be evaluated to improve the application of autologous MSCs. This review aims to present the available data on the senescence of MSCs, its relationship with hyperglycemia, and the strategies to suppress the senescence of MSCs in a hyperglycemic environment.
Senescence
Regenerative Medicine
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Citations (32)
Senescence
Cellular senescence
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