Potentialities of Induced Pluripotent Stem (iPS) Cells for Treatment of Diseases
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Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine. Keywords: Induced pluripotent stem (iPS) cell, disease-specific iPS cell lines, drug discovery and development, toxicological studies, personalized medicine, regenerative medicine, Yamanaka Factors, blastomeres, HMG-box, histone acetyltransferases, c-Myc, Nanog, pluripotency, retrovirus, lentivirus, doxycycline, keratinocytes, neurodegenerative disorders, amyotrophic lateral sclerosis, spinal muscular atrophy, Huntington's disease, Alzheimer's disease, Parkinson's disease, Anderson-Fabry disease, transplantationKeywords:
Reprogramming
Regenerative Medicine
Homeobox protein NANOG
Cultured mouse spermatogonial stem cells (SSCs), also known as germline stem cells (GSCs), revert back to pluripotent state either spontaneously or upon being modified genetically. However, the reprogramming efficiencies are low, and the underlying mechanism remains poorly understood. In the present study, we conducted transcriptomic analysis and found that many transcription factors and epigenetic modifiers were differentially expressed between GSCs and embryonic stem cells. We failed in reprogramming GSCs to pluripotent state using the Yamanaka 4 Factors, but succeeded when Nanog and Tet1 were included. More importantly, reprogramming was also achieved with Nanog alone in a p53-deficient GSC line with an efficiency of 0.02‰. These GSC-derived-induced pluripotent stem cells possessed in vitro and in vivo differentiation abilities despite the low rate of chimera formation, which might be caused by abnormal methylation in certain paternally imprinted genes. Together, these results show that GSCs can be reprogrammed to pluripotent state via multiple avenues and contribute to our understanding of the mechanisms of GSC reprogramming.
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Homeobox protein NANOG
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ALS : amyotrophic lateral sclerosis UMN : upper motor neuron LMN : lower motor neuron fALS : familial amyotrophic lateral sclerosis sALS : sporadic amyotrophic lateral sclerosis Amyotrophic lateral sclerosis (ALS) reflects a heterogeneous group of neurodegenerative disorders unified by
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Lower motor neuron
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Sera from patients with amyotrophic lateral sclerosis (ALS) were applied to mouse anterior horn cells in tissue culture. No unique toxic effect was observed when compared with sera from normal and non-ALS neuromuscular disease subjects.
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Nanog gene is a new transcription factor reported in 2003 to be expressed in blastular inner cell mass,primitive germ cells and embryonic stem cells.Nanog plays a crucial role in the maintenance of self-renewal and pluripotency of embryonic stem cells.The research of Nanog is of great significance for developmental biology,regenerative medicine,and development of new drugs.Recently,Nanog gene has been extensively studied for its expression and mechanism of action in embryonic stem cells,somatic cells,and tumor cells.The regulation of Nanog gene is predicted to be associated with the occurrence and progress of cancer,as a promising target for prospective tumor treatment.The further investigation into the expression and regulation mechanism of Nanog gene helps to explore the novel preventive and therapeutic regimens of cancer.
Homeobox protein NANOG
Nanog Homeobox Protein
Rex1
Regenerative Medicine
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The transcription factors Oct4, Sox2 and Nanog form a triumvirate of regulatory proteins governing efficient maintenance of pluripotent cell identity. However, in contrast to Oct4 and Sox2, whose protein levels are relatively constant in undifferentiated mouse ES cells, Nanog levels fluctuate widely. Here, we discuss the effect of altering the dose of Nanog on self-renewal efficiency. The key role of Nanog as a self-renewal rheostat and the fact that fluctuations in Nanog level allow entry of Nanog-low cells into a differentiation-prone state are presented in relation to interactions of Nanog not only with itself but also with its partner proteins.
Homeobox protein NANOG
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Nanog 是明确地在老鼠表示的一个新奇抄写因素胚胎的干细胞(mES 房间) 。Nanog 在维持 ES 房间的多力量起一个必要作用，这被报导了。Nanog 的表示对 ES 房间区别很敏感，使 Nanog 成为显示 ES 房间的地位的最好的标记之一。在这研究，我们开发了一个有效方法构造驾驶的 Nanog 倡导者 EGFP 记者系统基于袋子相应再结合。我们进一步产生了一根 Nanog-EGFP 记者 mES 房间线。这根记者 mES 房间线展出了正常 mES 房间的类似于那些的特征，并且 EGFP 记者高效地反映了 Nanog 的表示，显示 mES 房间的区别地位。Weachieved 研究 mES 房间的自强和区别的一个可靠试验性的记者系统。系统能在 mES 房间在 Nanog 和另外的相关因素的表示和规定上的 mES 房间和研究的文化系统上便于研究。
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Nanog Homeobox Protein
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Amyotrophic lateral sclerosis is a rarely seen degenerative disease which involves the upper and lower motor neuron.In the past few years,significant progresses have been made in this disease.The article reviews the current diagnosis and treatment of amyotrophic lateral sclerosis.
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Direct reprogramming of somatic cells into a pluripotent state has been achieved with a set of just four transcription factors. Many scientists and medical doctors are trying to elucidate the causes of intractable diseases and discover new drugs using the newest types of technology. Various methods have been developed to produce clinical‐grade fully reprogrammed cells for cell transplantation therapy. Augmenting agents, such as small‐molecules, have been extensively screened to improve the reprogramming efficiency. The molecular mechanisms of reprogramming have been revealed by embryonic stem cell research. The accumulation of knowledge by the pioneers has driven the reprogramming field. In the present article, the contents of gift boxes from the studies of pluripotency to the nuclear reprogramming field are introduced.
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Abstract Phosphorylated TDP-43 (pTDP-43) aggregates in the cytoplasm of motor neurons and neuroglia in the brain are one of the pathological hallmarks of amyotrophic lateral sclerosis. Although the axons exceed the total volume of motor neuron soma by several orders of magnitude, systematic studies investigating the presence and distribution of pTDP-43 aggregates within motor nerves are still lacking. The aim of this study is to define the TDP-43/pTDP-43 pathology in diagnostic motor nerve biopsies performed on a large cohort of patients presenting with a lower motor neuron syndrome and to assess whether this might be a discriminating tissue biomarker for amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis cases. We retrospectively evaluated 102 lower motor neuron syndrome patients referred to our centre for a diagnostic motor nerve biopsy. Histopathological criteria of motor neuron disease and motor neuropathy were applied by two independent evaluators, who were blind to clinical data. TDP-43 and pTDP-43 were evaluated by immunohistochemistry, and results compared to final clinical diagnosis. We detected significant differences between amyotrophic lateral sclerosis and non-amyotrophic lateral sclerosis cases in pTDP-43 expression in myelinated fibres: axonal accumulation was detected in 98.2% of patients with amyotrophic lateral sclerosis versus 30.4% of non-amyotrophic lateral sclerosis samples (P < 0.0001), while concomitant positive staining in Schwan cell cytoplasm was found in 70.2% of patients with amyotrophic lateral sclerosis versus 17.4% of patients who did not have amyotrophic lateral sclerosis (P < 0.001). Importantly, we were also able to detect pTDP-43 aggregates in amyotrophic lateral sclerosis cases displaying normal features at standard histopathological analysis. Our findings demonstrated that a specific pTDP-43 signature is present in the peripheral nervous system of patients with amyotrophic lateral sclerosis, and could be exploited as a specific, accessible tissue biomarker. The detection of pTDP-43 aggregates within motor nerves of living patients with amyotrophic lateral sclerosis, occurring before axonal degeneration, suggests that this is an early event that may contribute to amyotrophic lateral sclerosis pathogenesis.
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Gingival overgrowth is a common side effect of medication with the immunosuppressant cyclosporine A (CsA). This study proposed to verify whether Nanog, an embryonic stem cell marker, contributes to gingival overgrowth stimulated with CsA in human gingival fibroblasts (HGFs).The effect of CsA on HGFs was used to elucidate whether Nanog expression could be induced by CsA using quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. Cell growth in CsA-treated HGFs with Nanog lentivirus-mediated short hairpin RNA interference knockdown was evaluated by tetrazolium bromide reduction assay.CsA upregulated Nanog transcript in HGFs in a dose-dependent manner (P < 0.05). CsA was also shown to increase Nanog protein expression in HGFs in a dose-dependent manner (P < 0.05). In addition, downregulation of Nanog by lentiviral infection significantly inhibited CsA-stimulated cell growth in HGFs (P < 0.05).CsA upregulated Nanog expression and cell growth in HGFs, while silencing Nanog effectively reversed these phenomena. Nanog may act as a major switch in the pathogenesis of CsA-induced gingival overgrowth.
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