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The past, present and future of bovine pluripotent stem cells: a brief overview

Xiuchun TIAN

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 3-7 doi: 10.15302/J-FASE-2018247

摘要：

Although the pursuit of bovine embryonic stem cells started more than 26 years ago for the purpose of gene-targeting, true pluripotent stem cells in this economically important species are still elusive. With the rapid advances in genome-editing and cloning using homologously recombined somatic cells, the need for pluripotent stem cells for precise genetic modification in any species became questionable. With the pig being the better model for human regenerative biology, the identification of the commonalities and uniqueness of the pluripotency circuitry across mammalian species may be the main objective for studying pluripotent stem cells in the bovine.

关键词： bovine     embryonic     induced     pluripotent stem cells    

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Porcine pluripotent stem cells: progress, challenges and prospects

Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 8-27 doi: 10.15302/J-FASE-2018233

摘要：

Pluripotent stem cells (PSCs) are characterized by their capacity for high self-renewal and multiple differentiation potential and include embryonic stem cells, embryonic germ cells and induced PSCs. PSCs provide a very suitable model for the studies of human diseases, drugs screening, regenerative medicine and developmental biology research. Pigs are considered as an ideal model for preclinical development of human xenotransplantation, therapeutic approaches and regenerative medicine because of their size and physiological similarity to humans. However, lack of knowledge about the derivation, characterization and pluripotency mechanisms of porcine PSCs hinders progress in these biotechnologies. In this review, we discuss the latest progress on porcine PSCs generation, evaluation criteria for pluripotency, the scientific and technical questions arising from these studies. We also introduce our perspectives on porcine PSC research, in the hope of providing new ideas for generating naive porcine PSCs and animal breeding.

关键词： embryonic germ cells     embryonic stem cells     induced pluripotent stem cells     pigs     pluripotent stem cells    

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Progress, problems and prospects of porcine pluripotent stem cells

Hanning WANG,Yangli PEI,Ning LI,Jianyong HAN

《农业科学与工程前沿（英文）》 2014年 第1卷 第1期   页码 6-15 doi: 10.15302/J-FASE-2014009

摘要： Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced PSCs (iPSCs), can differentiate into cells of the three germ layers, suggesting that PSCs have great potential for basic developmental biology research and wide applications for clinical medicine. Genuine ESCs and iPSCs have been derived from mice and rats, but not from livestock such as the pig—an ideal animal model for studying human disease and regenerative medicine due to similarities with human physiologic processes. Efforts to derive porcine ESCs and iPSCs have not yielded high-quality PSCs that can produce chimeras with germline transmission. Thus, exploration of the unique porcine gene regulation network of preimplantation embryonic development may permit optimization of culture systems for raising porcine PSCs. Here we summarize the recent progress in porcine PSC generation as well as the problems encountered during this progress and we depict prospects for generating porcine naive PSCs.

关键词： induced pluripotent stem cells     embryonic stem cells     pig     reprogramming    

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Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review

Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 28-32 doi: 10.15302/J-FASE-2018222

摘要：

Primordial germ cells (PGCs) are regarded as unipotent cells that can produce only either spermatogonia or oocytes. However, PGCs can be converted into the pluripotent state by first dedifferentiation to embryonic germ cells and then by reprogramming to induce them to become pluripotent stem cells (iPSCs). These two stages can be completely implemented with mouse cells. However, authentic porcine iPSCs have not been established. Here, we discuss recent advances in the stem cell field for obtaining iPSCs from PGCs. This knowledge will provide some clues which will contribute to the regulation of reprogramming to pluripotency in farm species.

关键词： pig     pluripotent stem cells     primordial germ cells     reprogramming    

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Cell therapy for the treatment of reproductive diseases and infertility: an overview from the mechanism to the clinic alongside diagnostic methods

《医学前沿（英文）》 2022年 第16卷 第6期   页码 827-858 doi: 10.1007/s11684-022-0948-8

摘要： Infertility is experienced by 8%–12% of adults in their reproductive period globally and has become a prevalent concern. Besides routine therapeutic methods, stem cells are rapidly being examined as viable alternative therapies in regenerative medicine and translational investigation. Remarkable progress has been made in understanding the biology and purpose of stem cells. The affected pluripotent stem cells (iPSCs) and mesenchymal stem cells (MSCs) are further studied for their possible use in reproductive medicine, particularly for infertility induced by premature ovarian insufficiency and azoospermia. Accordingly, this study discusses current developments in the use of some kinds of MSCs such as adipose-derived stem cells, bone marrow stromal cells, umbilical cord MSCs, and menstrual blood MSCs. These methods have been used to manage ovarian and uterine disorders, and each technique presents a novel method for the therapy of infertility.

关键词： infertility     stem cell therapy     mesenchymal stem cells     pluripotent stem cells    

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SALL4 maintains self-renewal of porcine pluripotent stem cells through downregulation of OTX2

Ning WANG, Sile WANG, Yaxian WANG, Yuanxing CAI, Fan YANG, Huayan WANG

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 81-92 doi: 10.15302/J-FASE-2017180

摘要：

Sall4 as one of the spalt family members contains several alternative splicing variants, which are differentially expressed and has a key role in maintaining pluripotent stem cells. However, the molecular features and function of SALL4 have not been well elucidated in porcine induced pluripotent stem cells (piPSCs). In this study, we identified splice variants and found two splicing variants through analysis of the porcine transcriptome data derived from piPSCs. SALL4A was only detected in piPSCs but SALL4B was globally expressed in porcine tissues and piPSCs. The level of SALL4B was significantly reduced when piPSCs differentiation occurred, however, the expression of SALL4A was not affected, indicating that SALL4B may be essential for the maintenance of piPSCs self-renewal. Overexpression of SALL4A and SALL4B in PEF cells could significantly stimulated expression of endogenous pluripotent genes, when SALL4B significantly promoted OCT4 expression. Conversely, SALL4A significantly promoted KLF4 expression. Additionally, both SALL4A and SALL4B could repress promoter activity in a dose-dependent manner. Conversely, OTX2 also negatively regulated SALL4 expression. These observations indicate that a negative feedback regulatory mechanism may exist between SALL4 and OTX2, which is useful for the maintenance of the self-renewal of piPSCs.

关键词： OTX2     pluripotency     pig     SALL4     transcription regulation    

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Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation

《医学前沿（英文）》 2022年 第16卷 第3期   页码 429-441 doi: 10.1007/s11684-021-0842-9

摘要： The local microenvironment is essential to stem cell-based therapy for ischemic stroke, and spatiotemporal changes of the microenvironment in the pathological process provide vital clues for understanding the therapeutic mechanisms. However, relevant studies on microenvironmental changes were mainly confined in the acute phase of stroke, and long-term changes remain unclear. This study aimed to investigate the microenvironmental changes in the subacute and chronic phases of ischemic stroke after stem cell transplantation. Herein, induced pluripotent stem cells (iPSCs) and neural stem cells (NSCs) were transplanted into the ischemic brain established by middle cerebral artery occlusion surgery. Positron emission tomography imaging and neurological tests were applied to evaluate the metabolic and neurofunctional alterations of rats transplanted with stem cells. Quantitative proteomics was employed to investigate the protein expression profiles in iPSCs-transplanted brain in the subacute and chronic phases of stroke. Compared with NSCs-transplanted rats, significantly increased glucose metabolism and neurofunctional scores were observed in iPSCs-transplanted rats. Subsequent proteomic data of iPSCs-transplanted rats identified a total of 39 differentially expressed proteins in the subacute and chronic phases, which are involved in various ischemic stroke-related biological processes, including neuronal survival, axonal remodeling, antioxidative stress, and mitochondrial function restoration. Taken together, our study indicated that iPSCs have a positive therapeutic effect in ischemic stroke and emphasized the wide-ranging microenvironmental changes in the subacute and chronic phases.

关键词： ischemic stroke     microenvironment     induced pluripotent stem cells (iPSCs)     positron emission tomography (PET)     quantitative proteomics    

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Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity

Chuanfeng Wu, Cynthia E. Dunbar

《医学前沿（英文）》 2011年 第5卷 第4期   页码 356-371 doi: 10.1007/s11684-011-0159-1

摘要： Virus-based vectors are widely used in hematopoietic stem cell (HSC) gene therapy, and have the ability to integrate permanently into genomic DNA, thus driving long-term expression of corrective genes in all hematopoietic lineages. To date, HSC gene therapy has been successfully employed in the clinic for improving clinical outcomes in small numbers of patients with X-linked severe combined immunodeficiency (SCID-X1), adenosine deaminase deficiency (ADA-SCID), adrenoleukodystrophy (ALD), thalassemia, chronic granulomatous disease (CGD), and Wiskott-Aldrich syndrome (WAS). However, adverse events were observed during some of these HSC gene therapy clinical trials, linked to insertional activation of proto-oncogenes by integrated proviral vectors leading to clonal expansion and eventual development of leukemia. Numerous studies have been performed to understand the molecular basis of vector-mediated genotoxicity, with the aim of developing safer vectors and lower-risk gene therapy protocols. This review will summarize current information on the mechanisms of insertional mutagenesis in hematopoietic stem and progenitor cells due to integrating gene transfer vectors, discuss the available assays for predicting genotoxicity and mapping vector integration sites, and introduce newly-developed approaches for minimizing genotoxicity as a way to further move HSC gene therapy forward into broader clinical application.

关键词： gene therapy     hematopoietic stem cells     insertional mutagenesis     genotoxicity     induced pluripotent stem cell    

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诱导性多潜能干细胞(iPS)研究：现状与展望

韩为东,赵亚力,付小兵

《中国工程科学》 2009年 第11卷 第5期   页码 81-87

摘要：

通过特定的基因组合与转染可以将已分化的体细胞诱导重编程为多潜能干细胞（iPS），是近年来干细胞研究领域最令人瞩目的一项新的干细胞制造技术。与胚胎干细胞（ES）不同，iPS细胞的制造不需要毁损胚胎，因而不会涉及更多的伦理学问题。iPS的出现不仅为体细胞重编程去分化机制的研究注入了新的活力，而且为疾病发生发展相关机制研究与特异的细胞治疗，特别是再生医学带来新的曙光。目前，iPS的研究尚处于初级阶段，文章就iPS的研究现状与应用前景进行综述和展望。

关键词： 体细胞     重编程     iPS细胞    

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Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow

FANG Baijun, SONG Yongping, LIN Quande, ZHAO Chunhua, SHI Mingxia

《医学前沿（英文）》 2007年 第1卷 第2期   页码 185-191 doi: 10.1007/s11684-007-0035-1

摘要： Previously, we reported that a cell population derived from human fetal bone marrow (BM), termed here Flk1CD34 postembryonic pluripotent stem cells (PPSCs) that have the characteristics of mesenchymal stem cells (MSCs), could differentiate into ectodermal, endodermal and mesodermal cell types at the single cell level , and that these cells could also differentiate into the epithelium of liver, lung, gut, as well as the hematopoietic and endothelial lineages after transplantion into irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice. In this study, we further isolated pluripotent stem cells from human fetal heart, liver, muscle, lung, derma, kidney, and fat and then analyzed the characteristics and function of these stem cells. It was found that the phenotype of the culture-expanded pluripotent stem cells from different fetal tissues was similar to BM-derived Flk1CD34 PPSCs, i.e. Flk1 and CD44 positive, GlyA, CD34, CD45, class I-HLA and HLA-DR negative. Morphologically, these cells were fibroblast-like and the doubling time was about 30 h. More importantly, culture-expanded pluripotent stem cells from all these fetal tissues were able to differentiate into cells with morphologic and phenotypic characteristics of adipocytes, osteocytes, neurons, glial cells and hepatocytes. These pluripotent stem cells with characteristics similar to fetal BM-derived Flk1CD34 PPSCs can be selected and cultured from tissues other than the BM. This phenomenon may help explain the stem cell plasticity found in multiple human tissues. In addition, as fetal BM-derived Flk1CD34 PPSCs, these pluripotent stem cells from different fetal tissues had the capacity for self-renewal and multi-lineage differentiation even after being expanded for more than 40 population doublings . Thus, they may be an ideal source of stem cells for treatment of inherited or degenerative diseases.

关键词： endothelial     phenomenon     ectodermal     Flk1CD34 postembryonic     irradiated non-obese    

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Determination of telomerase activity in stem cells and non-stem cells of breast cancer

LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao

《医学前沿（英文）》 2007年 第1卷 第3期   页码 294-298 doi: 10.1007/s11684-007-0056-9

摘要： Although all normal tissue cells, including stem cells, are genetically homologous, variation in gene expression patterns has already determined the distinct roles for individual cells in the physiological process due to the occurrence of epigenetic modification. This is of special importance for the existence of tissue stem cells because they are exclusively immortal within the body, capable of selfreplicating and differentiating by which tissues renew and repair itself and the total tissue cell population maintains a steady-state. Impairment of tissue stem cells is usually accompanied by a reduction in cell number, slows down the repair process and causes hypofunction. For instance, chemotherapy usually leads to depression of bone marrow and hair loss. Cellular aging is closely associated with the continuous erosion of the telomere while activation of telomerase repairs and maintains telomeres, thus slowing the aging process and prolonging cell life. In normal adults, telomerase activation mainly presents in tissue stem cells and progenitor cells giving them unlimited growth potential. Despite the extensive demonstration of telomerase activation in malignancy (>80%), scientists found that heterogeneity also exists among the tumor cells and only minorities of cells, designated as cancer stem cells, undergo processes analogous to the self-renewal and differentiation of normal stem cells while the rest have limited lifespans. In this study, telomerase activity was measured and compared in breast cancer stem cells and non-stem cells that were phenotypically sorted by examining surface marker expression. The results indicated that cancer stem cells show a higher level of enzyme activity than non-stem cells. In addition, associated with the repair of cancer tissue (or relapse) after chemotherapy, telomerase activity in stem cells was markedly increased.
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Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration

null

《医学前沿（英文）》 2012年 第6卷 第1期   页码 41-47 doi: 10.1007/s11684-012-0175-9

摘要：

Umbilical cord mesenchymal stem cells (MSCs) are a unique, accessible, and non-controversial source of early stem cells that can be readily manipulated. As the most common pluripotent cell, bone marrow-derived MSCs display limitations with the progress of stem cell therapy. By contrast, umbilical cord-derived cells, which have plentiful resources, are more accessible. However, several uncertain aspects, such as the effect of donor selection or culture conditions, long-term therapeutic effects, product consistency, and potential tumorigenicity, are the bottleneck in this clinical therapy. MSCs are predicted to undergo an unprecedented development in clinical treatment when a generally acknowledged criterion emerges. In the current paper, we highlight the application of umbilical cord-derived MSCs in skin therapies based on our previous studies, as well as the achievements of our peers in this field. This paper focuses on the strategies, challenges, and potential of this novel therapy.

关键词： umbilical cord     mesenchymal stem cells     cutaneous regeneration    

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Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

《医学前沿（英文）》 2011年 第5卷 第4期   页码 372-378 doi: 10.1007/s11684-011-0164-4

摘要： Regenerative medicine is an emerging interdisciplinary field of research that uses several technological approaches including stem cells to repair tissues. Mesenchymal stem cells (MSCs), a type of adult stem cell, have generated a great amount of interest over the past decade in this field. Numerous studies have explored the role of MSCs in tissue repair and modulation of allogeneic immune responses. The mechanisms through which MSCs exert their therapeutic potential rely on some key properties of the cells as follows: the capacity to differentiate into osteoblasts, chondrocytes, adipocytes, cardiomyocytes, hepatocytes, endothelial, and neuronal cells; the ability to secrete multiple bioactive molecules capable of stimulating the recovery of injured cells and inhibiting inflammation; the lack of immunogenicity; and the ability to perform immunomodulatory functions. In the present review, we focus on these three aspects upon which the therapeutic effects of MSCs are mainly based. Furthermore, some pathological conditions under which the application of MSCs should be done with caution are also mentioned.

关键词： mesenchymal stem cells     differentiation     immunomodulation     regenerative medicine    

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Highlights for special issue on “Large Animal Stem Cells”

Jianyong HAN

《农业科学与工程前沿（英文）》 2019年 第6卷 第1期   页码 1-2 doi: 10.15302/J-FASE-2019251

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GID complex regulates the differentiation of neural stem cells by destabilizing TET2

《医学前沿（英文）》 doi: 10.1007/s11684-023-1007-9

摘要： Brain development requires a delicate balance between self-renewal and differentiation in neural stem cells (NSC), which rely on the precise regulation of gene expression. Ten-eleven translocation 2 (TET2) modulates gene expression by the hydroxymethylation of 5-methylcytosine in DNA as an important epigenetic factor and participates in the neuronal differentiation. Yet, the regulation of TET2 in the process of neuronal differentiation remains unknown. Here, the protein level of TET2 was reduced by the ubiquitin-proteasome pathway during NSC differentiation, in contrast to mRNA level. We identified that TET2 physically interacts with the core subunits of the glucose-induced degradation-deficient (GID) ubiquitin ligase complex, an evolutionarily conserved ubiquitin ligase complex and is ubiquitinated by itself. The protein levels of GID complex subunits increased reciprocally with TET2 level upon NSC differentiation. The silencing of the core subunits of the GID complex, including WDR26 and ARMC8, attenuated the ubiquitination and degradation of TET2, increased the global 5-hydroxymethylcytosine levels, and promoted the differentiation of the NSC. TET2 level increased in the brain of the Wdr26+/− mice. Our results illustrated that the GID complex negatively regulates TET2 protein stability, further modulates NSC differentiation, and represents a novel regulatory mechanism involved in brain development.

关键词： TET2     GID complex     neural stem cells     differentiation of neurons    

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标题 作者 时间 类型 操作

The past, present and future of bovine pluripotent stem cells: a brief overview

Xiuchun TIAN

期刊论文

Porcine pluripotent stem cells: progress, challenges and prospects

Jianyong HAN, Yi-Liang MIAO, Jinlian HUA, Yan LI, Xue ZHANG, Jilong ZHOU, Na LI, Ying ZHANG, Jinying ZHANG, Zhonghua LIU

期刊论文

Progress, problems and prospects of porcine pluripotent stem cells

Hanning WANG,Yangli PEI,Ning LI,Jianyong HAN

期刊论文

Reprogramming of the pig primordial germ cells into pluripotent stem cells: a brief review

Qijing LEI, Qin PAN, Shuai YU, Na LI, Shulin CHEN, Kuldip SIDHU, Jinlian HUA

期刊论文

Cell therapy for the treatment of reproductive diseases and infertility: an overview from the mechanism to the clinic alongside diagnostic methods

期刊论文

SALL4 maintains self-renewal of porcine pluripotent stem cells through downregulation of OTX2

Ning WANG, Sile WANG, Yaxian WANG, Yuanxing CAI, Fan YANG, Huayan WANG

期刊论文

Quantitative proteomics revealed extensive microenvironmental changes after stem cell transplantation

期刊论文

Stem cell gene therapy: the risks of insertional mutagenesis and approaches to minimize genotoxicity

Chuanfeng Wu, Cynthia E. Dunbar

期刊论文

诱导性多潜能干细胞(iPS)研究：现状与展望

韩为东,赵亚力,付小兵

期刊论文

Pluripotent stem cells exhibiting similar characteristics can be isolated from human fetal bone marrow

FANG Baijun, SONG Yongping, LIN Quande, ZHAO Chunhua, SHI Mingxia

期刊论文

Determination of telomerase activity in stem cells and non-stem cells of breast cancer

LI Zhi, HE Yanli, ZHANG Jiahua, ZHANG Jinghui, HUANG Tao

期刊论文

Umbilical cord-derived mesenchymal stem cells: strategies, challenges, and potential for cutaneous regeneration

null

期刊论文

Mesenchymal stem cells hold promise for regenerative medicine

Shihua Wang, Xuebin Qu, Robert Chunhua Zhao

期刊论文

Highlights for special issue on “Large Animal Stem Cells”

Jianyong HAN

期刊论文

GID complex regulates the differentiation of neural stem cells by destabilizing TET2

期刊论文