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Induced Pluripotent Stem Cells Generated from Reprogramming Differentiated Cells by Defined Factors
分化细胞经特定因子诱导重编程为多能干细胞

Xiaoyu Xi,Jianxin Chu,Xuejin Chen,
夏小雨
,褚建新,陈学进

生物工程学报 , 2008,
Abstract: Embryonic stem cell is promising for regenerative medicine. However, its application is hampered by the utilization of eggs in most established methods. Recently, a new pluripotent stem cell establishing method was reported that, mouse and human differentiated cells could be induced reprogrammed into a pluripotent state by expressing exogenetic stem factors such as Oct4, Sox2, et al, through retroviral transduction. This approach avoiding egg use is a great breakthrough not only in stem cell technology but also present theory hypothesis of reprogramming. Here these works were reviewed in this article. Both the mechanism of induced reprogramming and the prospects of induced pluripotent stem cells were discussed.
Current protocols in the generation of pluripotent stem cells: theoretical, methodological and clinical considerations
Brad B Swelstad, Candace L Kerr
Stem Cells and Cloning: Advances and Applications , 2010, DOI: http://dx.doi.org/10.2147/SCCAA.S8051
Abstract: rrent protocols in the generation of pluripotent stem cells: theoretical, methodological and clinical considerations Review (7318) Total Article Views Authors: Brad B Swelstad, Candace L Kerr Published Date December 2009 Volume 2010:3 Pages 13 - 27 DOI: http://dx.doi.org/10.2147/SCCAA.S8051 Brad B Swelstad, Candace L Kerr Institute for Cell Engineering, Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, MA, USA Abstract: Pluripotent stem cells have been derived from various embryonic, fetal and adult sources. Embryonic stem cells (ESCs) and parthenogenic ESCs (pESCs) are derived from the embryo proper while embryonic germ cells (EGCs), embryonal carcinoma cells (ECCs), and germ-line stem cells (GSC) are produced from germ cells. ECCs were the first pluripotent stem cell lines established from adult testicular tumors while EGCs are generated in vitro from primordial germ cells (PGCs) isolated in late embryonic development. More recently, studies have also demonstrated the ability to produce GSCs from adult germ cells, known as spermatogonial stem cells. Unlike ECCs, the source of GSCs are normal, non-cancerous adult tissue. The study of these unique cell lines has provided information that has led to the ability to reprogram somatic cells into an ESC-like state. These cells, called induced pluripotent stem cells (iPSCs), have been derived from a number of human fetal and adult origins. With the promises pluripotent stem cells bring to cell-based therapies there remain several considerations that need to be carefully studied prior to their clinical use. Many of these issues involve understanding key factors regulating their generation, including those which define pluripotency. In this regard, the following article discusses critical aspects of pluripotent stem cell derivation and current issues about their therapeutic potential.
Current protocols in the generation of pluripotent stem cells: theoretical, methodological and clinical considerations  [cached]
Brad B Swelstad,Candace L Kerr
Stem Cells and Cloning: Advances and Applications , 2009,
Abstract: Brad B Swelstad, Candace L KerrInstitute for Cell Engineering, Department of Obstetrics and Gynecology, Johns Hopkins University, Baltimore, MA, USAAbstract: Pluripotent stem cells have been derived from various embryonic, fetal and adult sources. Embryonic stem cells (ESCs) and parthenogenic ESCs (pESCs) are derived from the embryo proper while embryonic germ cells (EGCs), embryonal carcinoma cells (ECCs), and germ-line stem cells (GSC) are produced from germ cells. ECCs were the first pluripotent stem cell lines established from adult testicular tumors while EGCs are generated in vitro from primordial germ cells (PGCs) isolated in late embryonic development. More recently, studies have also demonstrated the ability to produce GSCs from adult germ cells, known as spermatogonial stem cells. Unlike ECCs, the source of GSCs are normal, non-cancerous adult tissue. The study of these unique cell lines has provided information that has led to the ability to reprogram somatic cells into an ESC-like state. These cells, called induced pluripotent stem cells (iPSCs), have been derived from a number of human fetal and adult origins. With the promises pluripotent stem cells bring to cell-based therapies there remain several considerations that need to be carefully studied prior to their clinical use. Many of these issues involve understanding key factors regulating their generation, including those which define pluripotency. In this regard, the following article discusses critical aspects of pluripotent stem cell derivation and current issues about their therapeutic potential.Keywords: pluripotency, stem cells, derivation, human
The Promise of Human Induced Pluripotent Stem Cells in Dental Research  [PDF]
Thekkeparambil Chandrabose Srijaya,Padmaja Jayaprasad Pradeep,Rosnah Binti Zain,Sabri Musa,Noor Hayaty Abu Kasim,Vijayendran Govindasamy
Stem Cells International , 2012, DOI: 10.1155/2012/423868
Abstract: Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC lines in vitro from patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders. 1. Introduction Human embryonic stem cells (hESCs) are pluripotent cells, which have remarkable proliferation ability to differentiate into any cell types of all three germ layers in a defined culture condition. Hence embryonic stem cells have been regarded as the most potent tool for experimental studies, drug screening, and regenerative medicine [1]. However, the ethical dilemmas regarding the donation or destruction of human embryos and the immunoincompatibility of hESCs have impeded its application in cell-based therapy [1]. In order to overcome these problems, reprogramming techniques have been introduced where somatic cells can be reversed into a pluripotent stem cell-like state. It is generally believed that induced pluripotent stem (iPSC) cells might demonstrate the potential for alleviating incurable diseases and aiding organ transplantation [2]. It has been shown that iPSCs can be derived efficiently from various human cell types [3–8]. An interesting observation is that the transcriptional and epigenetic features of iPSCs are reported to be similar to hESCs [9–11]. Nevertheless, further insights into the inherent similarities and differences between hESCs and iPSCs would be advantageous in understanding the reasons why the use of hESCs in clinical and translational applications has been held back [12, 13]. 2. Generation of Induced Pluripotent Stem Cells Induced pluripotent stem cells can be produced by forced expression of certain genes by reversing them to a pluripotent state similar to that of embryonic stem
Cortical interneurons from human pluripotent stem cells: prospects for neurological and psychiatric disease  [PDF]
Charles Arber,Meng Li
Frontiers in Cellular Neuroscience , 2013, DOI: 10.3389/fncel.2013.00010
Abstract: Cortical interneurons represent 20% of the cells in the cortex. These cells are local inhibitory neurons whose function is to modulate the firing activities of the excitatory projection neurons. Cortical interneuron dysfunction is believed to lead to runaway excitation underlying (or implicated in) seizure-based diseases, such as epilepsy, autism, and schizophrenia. The complex development of this cell type and the intricacies involved in defining the relative subtypes are being increasingly well defined. This has led to exciting experimental cell therapy in model organisms, whereby fetal-derived interneuron precursors can reverse seizure severity and reduce mortality in adult epileptic rodents. These proof-of-principle studies raise hope for potential interneuron-based transplantation therapies for treating epilepsy. On the other hand, cortical neurons generated from patient iPSCs serve as a valuable tool to explore genetic influences of interneuron development and function. This is a fundamental step in enhancing our understanding of the molecular basis of neuropsychiatric illnesses and the development of targeted treatments. Protocols are currently being developed for inducing cortical interneuron subtypes from mouse and human pluripotent stem cells. This review sets out to summarize the progress made in cortical interneuron development, fetal tissue transplantation and the recent advance in stem cell differentiation toward interneurons.
Advances in the study on induced pluripotent stem cells
Shuang Liu,EnKui Duan
Chinese Science Bulletin , 2008, DOI: 10.1007/s11434-008-0152-5
Abstract: Recently, the study on “induced pluripotent stem cells” (iPS cells) has made a great breakthrough, and it is considered as a new milestone in the history of life science. This progress has updated our traditional concepts about pluripotency control, and provided people with a brand-new strategy for somatic cell nuclear reprogramming. In virtue of its availability and stability, this method holds great potential in both biological and clinical research. In order to introduce this rising field of study, this paper starts with an overview of the development of iPS cell establishment, describes the key steps in generating iPS cells, elaborates several relevant scientific issues, and evaluates its current restrictions and promises in future research.
Advances in the study on induced pluripotent stem cells
LIU Shuang,DUAN EnKui,

科学通报(英文版) , 2008,
Abstract: Recently, the study on "induced pluripotent stem cells" (iPS cells) has made a great breakthrough, and it is considered as a new milestone in the history of life science. This progress has updated our tradi- tional concepts about pluripotency control, and provided people with a brand-new strategy for somatic cell nuclear reprogramming. In virtue of its availability and stability, this method holds great potential in both biological and clinical research. In order to introduce this rising field of study, this paper starts with an overview of the development of iPS cell establishment, describes the key steps in generating iPS cells, elaborates several relevant scientific issues, and evaluates its current restrictions and promises in future research.
Capturing Alzheimer's disease genomes with induced pluripotent stem cells: prospects and challenges
Mason A Israel, Lawrence SB Goldstein
Genome Medicine , 2011, DOI: 10.1186/gm265
Abstract: Alzheimer's disease (AD) is a common, fatal neurodegenerative disease that currently afflicts more than 35 million people worldwide [1]. With the increasing longevity and aging of many populations around the world, the devastation caused by AD to patients, their families, societies and economies is growing. Currently, there is no approved treatment with a proven disease-modifying effect [2].Mechanistic studies of AD generally rely on autopsy samples, which are limited in supply and contain the disease aftermath, or on animal models, which do not fully recapitulate AD pathogenesis. Consequently, it has been very difficult to elucidate the initiating events of AD. Furthermore, recent clinical trials for AD have been largely disappointing. A proper understanding of the initiating events of AD and the existence of live disease models that accurately recapitulate the pathogenesis would lead to a much better informed therapeutic development effort.Within the past few years, genome-wide association studies (GWAS) of AD have uncovered new susceptibility genes for the sporadic form of AD (sAD), and many of these genes appear to be part of similar biochemical pathways. Nevertheless, creating systems that can validate and study these genes has been a major challenge.Induced pluripotent stem cell (iPSC) technology has the potential to capture the genomes of AD patients and to generate live cellular models of both the familial AD (fAD) and sAD. These models might allow us to identify the earliest events of AD, to investigate aspects of AD pathogenesis that are not recapitulated in animal models, and to validate and build upon findings from GWAS.In this review, we begin by summarizing our current understanding of the genetics and genomics of AD, and continue by discussing recent studies of iPSCs that are relevant to the study of AD. As AD is a complex neurodegenerative disease, we focus on studies of the genomic fidelity of iPSCs, on research on the differentiation of iPSCs into
Pluripotency of induced pluripotent stem cells
Lan Kang, Shaorong Gao
Journal of Animal Science and Biotechnology , 2012, DOI: 10.1186/2049-1891-3-5
Abstract: An iPS cell is induced from a non-pluripotent cell, but possesses pluripotency similar to that of ES cells. Takahashi and Yamanaka (2006) first achieved this landmark breakthrough by reprograming mouse embryonic fibroblasts (MEFs) into this new type of pluripotent stem cell via the ectopic expression of only four transcription factors, namely Oct4, Sox2, Klf4 and c-Myc. This new procedure circumvented the need for an oocyte, which is required by an earlier method of generating customized pluripotent stem cells termed somatic cell nuclear transfer (SCNT)-mediated nuclear reprogramming [1-3]. Since the discovery of iPS cells, the field has attracted a great amount of scientific and public attention because of the undefined mechanism by which the developmental potential of the cells is reverted and the potential for clinical applications using patient specific iPS cells. The generation of iPS cells from individual patients has raised the hope of treatments for numerous degenerative and genetic diseases [4-11].Unlike normal fertilization or the generation of SCNT-ES cells, the creation of iPS cells is a longer process that results in a heterogeneous mixture of cells with various developmental potentials. In the primary culture, iPS cells are usually present together with the original somatic cells, transformed cells and partially reprogrammed cells. Indeed, iPS cells are only approximately 0.1% to 1% of the total cells used for reprogramming. Moreover, only very small proportions of these cells are fully reprogrammed based on stringent criteria for evaluating pluripotency. Therefore, it is necessary to establish a molecular standard to distinguish fully reprogrammed iPS cells from those that are partially reprogrammed, especially for human iPS cells that may eventually be used for clinical applications.In the present review, we will summarize the most recent progress toward understanding the pluripotency of mouse iPS cells at the functional and molecular levels. We anti
Tapping Stem Cells to Target AMD: Challenges and Prospects  [PDF]
Caroline Brandl,Felix Grassmann,Julia Riolfi,Bernhard H. F. Weber
Journal of Clinical Medicine , 2015, DOI: 10.3390/jcm4020282
Abstract: Human pluripotent stem cells (hPSCs) are increasingly gaining attention in biomedicine as valuable resources to establish patient-derived cell culture models of the cell type known to express the primary pathology. The idea of “a patient in a dish” aims at basic, but also clinical, applications with the promise to mimic individual genetic and metabolic complexities barely reflected in current invertebrate or vertebrate animal model systems. This may particularly be true for the inherited and complex diseases of the retina, as this tissue has anatomical and physiological aspects unique to the human eye. For example, the complex age-related macular degeneration (AMD), the leading cause of blindness in Western societies, can be attributed to a large number of genetic and individual factors with so far unclear modes of mutual interaction. Here, we review the current status and future prospects of utilizing hPSCs, specifically induced pluripotent stem cells (iPSCs), in basic and clinical AMD research, but also in assessing potential treatment options. We provide an outline of concepts for disease modelling and summarize ongoing and projected clinical trials for stem cell-based therapy in late-stage AMD.
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