scholarly journals Induced Pluripotent Stem Cells

2018 ◽  
pp. 16-22
Author(s):  
Abdullah El-Sayes
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Scientific Progress ◽  
Ips Cells ◽  
Ips Cell ◽  
Pluripotent State ◽  
Scientific Investigations ◽  
Induced Pluripotent ◽  
Mouse Somatic Cell

The isolation of human embryonic stem cells in 1998 has since fueled the ideology that stem cells may eventually be used for human disease therapies as well as the regeneration of tissues and organs. The transformation of somatic cells to a pluripotent state via somatic nuclear transfer and embryonic stem cell fusion brought the scientific community nearer to understanding the molecular mechanisms that govern cellular pluripotency. In 2006, the first induced pluripotent stem (iPS) cell was reported, where a mouse somatic cell was successfully converted to a pluripotent state via transduction of four essential factors. This cellular breakthrough has allowed for robust scientific investigations of human diseases that were once extremely difficult to study. Scientists and pharmaceuticals now use iPS cells as means for disease investigations, drug development and cell or tissue transplantation. There is little doubt that scientific progress on iPS cells will change many aspects of medicine in the next couple of decades.

Human induced pluripotent stem cells are capable of B-cell lymphopoiesis

Blood ◽  
2011 ◽  
Vol 117 (15) ◽  
pp. 4008-4011 ◽  
Author(s):  
Lee Carpenter ◽  
Ram Malladi ◽  
Cheng-Tao Yang ◽  
Anna French ◽  
Katherine J. Pilkington ◽  
...  
Keyword(s):  
Stem Cells ◽  
B Cell ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Ips Cell ◽  
Lymphoid Lineage ◽  
Human Ips Cells ◽  
Induced Pluripotent ◽  
First Time ◽  
Unique Potential

Abstract Induced pluripotent stem (iPS) cells offer a unique potential for understanding the molecular basis of disease and development. Here we have generated several human iPS cell lines, and we describe their pluripotent phenotype and ability to differentiate into erythroid cells, monocytes, and endothelial cells. More significantly, however, when these iPS cells were differentiated under conditions that promote lympho-hematopoiesis from human embryonic stem cells, we observed the formation of pre-B cells. These cells were CD45+CD19+CD10+ and were positive for transcripts Pax5, IL7αR, λ-like, and VpreB receptor. Although they were negative for surface IgM and CD5 expression, iPS-derived CD45+CD19+ cells also exhibited multiple genomic D-JH rearrangements, which supports a pre–B-cell identity. We therefore have been able to demonstrate, for the first time, that human iPS cells are able to undergo hematopoiesis that contributes to the B-cell lymphoid lineage.

Abstract 244: A Novel Method for the Generation of Induced Pluripotent Stem Cells From Human Peripheral Blood

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Han-Mo Yang ◽  
Ju-Young Kim ◽  
Yoo-Wook Kwon ◽  
Hyo-Soo Kim
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Peripheral Blood ◽  
High Efficiency ◽  
Human Peripheral Blood ◽  
Gene Transfection ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Ips Cell ◽  
Induced Pluripotent

Background: In terms of the generation of induced pluripotent stem(iPS) cells, one of the important issues for clinical applications is cell source. Human peripheral blood is one of the easily accessible cell sources. However, isolated peripheral blood cells have shown low gene transfection efficiency and inconveniences requiring specific methods to isolate. Here, we report a novel population of peripheral blood-derived stem cells, which can be easily reprogrammed to iPS cells. Methods and Results: We cultured peripheral blood mononuclear cells (PBMC) from human peripheral blood and seeded on the fibronectin-coated plate. We observed adherent cells from as early as 5 days after the start of culture and those cells gradually formed colonies. We were able to isolate these cells with very high efficiency. Furthermore, we have also confirmed that these cells can be differentiated to osteogenic, adipogenic, and myogenic-lineage cells. Therefore, we named these cells circulating multipotent adult stem cell. We were successful in generating iPS cells with these cells. These cells showed enhanced efficiency of gene transduction, compared to the human dermal fibroblast. We obtained reprogrammed colonies in 8 days after 4 factor virus transduction without feeder cells. We identified our iPS cells had similar features to embryonic stem cell in morphology, gene expression, epigenetic state and ability to differentiate into the three germ layers. We obtained more than 46 iPS cell lines from PBMC of patients with cardiovascular disease and normal volunteers. Conclusions: Our study showed new methods to isolate stem cells from peripheral blood and to generate iPS cells with high efficacy. This result suggests that our new approach could be one of ideal methods for clinical application of iPS cells in future.

scholarly journals iPS-Cell Technology and the Problem of Genetic Instability—Can It Ever Be Safe for Clinical Use?

2019 ◽  
Vol 8 (3) ◽  
pp. 288 ◽  
Author(s):  
Stephen Attwood ◽  
Michael Edel
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Embryonic Stem ◽  
Great Promise ◽  
Clinical Use ◽  
Medicinal Products ◽  
Ips Cell ◽  
Factors Affecting ◽  
Induced Pluripotent ◽  
Stem Cell Therapeutics

The use of induced Pluripotent Stem Cells (iPSC) as a source of autologous tissues shows great promise in regenerative medicine. Nevertheless, several major challenges remain to be addressed before iPSC-derived cells can be used in therapy, and experience of their clinical use is extremely limited. In this review, the factors affecting the safe translation of iPSC to the clinic are considered, together with an account of efforts being made to overcome these issues. The review draws upon experiences with pluripotent stem-cell therapeutics, including clinical trials involving human embryonic stem cells and the widely transplanted mesenchymal stem cells. The discussion covers concerns relating to: (i) the reprogramming process; (ii) the detection and removal of incompletely differentiated and pluripotent cells from the resulting medicinal products; and (iii) genomic and epigenetic changes, and the evolutionary and selective processes occurring during culture expansion, associated with production of iPSC-therapeutics. In addition, (iv) methods for the practical culture-at-scale and standardization required for routine clinical use are considered. Finally, (v) the potential of iPSC in the treatment of human disease is evaluated in the light of what is known about the reprogramming process, the behavior of cells in culture, and the performance of iPSC in pre-clinical studies.

scholarly journals PRMT7: A Pivotal Arginine Methyltransferase in Stem Cells and Development

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Bingyuan Wang ◽  
Mingrui Zhang ◽  
Zhiguo Liu ◽  
Yulian Mu ◽  
Kui Li
Keyword(s):  
Stem Cells ◽  
Developmental Delay ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Embryonic Stem ◽  
Arginine Methylation ◽  
Male Reproduction ◽  
Protein Arginine Methyltransferases ◽  
Underlying Mechanisms ◽  
Induced Pluripotent

Protein arginine methylation is a posttranslational modification catalyzed by protein arginine methyltransferases (PRMTs), which play critical roles in many biological processes. To date, nine PRMT family members, namely, PRMT1, 2, 3, 4, 5, 6, 7, 8, and 9, have been identified in mammals. Among them, PRMT7 is a type III PRMT that can only catalyze the formation of monomethylarginine and plays pivotal roles in several kinds of stem cells. It has been reported that PRMT7 is closely associated with embryonic stem cells, induced pluripotent stem cells, muscle stem cells, and human cancer stem cells. PRMT7 deficiency or mutation led to severe developmental delay in mice and humans, which is possibly due to its crucial functions in stem cells. Here, we surveyed and summarized the studies on PRMT7 in stem cells and development in mice and humans and herein provide a discussion of the underlying molecular mechanisms. Furthermore, we also discuss the roles of PRMT7 in cancer, adipogenesis, male reproduction, cellular stress, and cellular senescence, as well as the future perspectives of PRMT7-related studies. Overall, PRMT7 mediates the proliferation and differentiation of stem cells. Deficiency or mutation of PRMT7 causes developmental delay, including defects in skeletal muscle, bone, adipose tissues, neuron, and male reproduction. A better understanding of the roles of PRMT7 in stem cells and development as well as the underlying mechanisms will provide information for the development of strategies for in-depth research of PRMT7 and stem cells as well as their applications in life sciences and medicine.

Abstract 340: From Stem Cells to Cardiomyocytes: HDAC1 Induces Cardiovascular Differentiation by Regulating SOX17-BMP2 Expression in Early Development.

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Eneda Hoxha ◽  
Erin Lambers ◽  
Veronica Ramirez ◽  
Prasanna Krishnamurthy ◽  
Suresh Verma ◽  
...  
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Es Cells ◽  
Ips Cells ◽  
Full Potential ◽  
Pluripotent Cells ◽  
Differentiation Potential ◽  
Histone Deacetylase 1 ◽  
Specific Differentiation ◽  
Induced Pluripotent

Cardiomyocytes derived from embryonic and induced pluripotent stem cells (ES/iPS) provide an excellent source for cell replacement therapies following myocardial ischemia. However, some of the obstacles in the realization of the full potential of iPS/ES cells arise from incomplete and poorly understood molecular mechanisms and epigenetic modifications that govern their cardiovascular specific differentiation. We identified Histone Deacetylase 1 (HDAC1) as a crucial regulator in early differentiation of mES and iPS cells. We propose a novel pathway in which HDAC1 regulates cardiovascular differentiation by regulating SOX17 which in turn regulates BMP2 signaling in differentiating pluripotent cells. Utilizing stable HDAC1 knock-down (HDAC1-KD) cell lines, we report an essential role for HDAC1 in deacetylating regulatory regions of pluripotency-associated genes during early cardiovascular differentiation. HDAC1-KD cells show severely repressed cardiomyocyte differentiation potential. We propose a novel HDAC1-BMP2-SOX17 dependent pathway through which deacetylation of pluripotency associated genes leads to their suppression and allows for early cardiovascular-associated genes to be expressed and differentiation to occur. Furthermore, we show that HDAC1 affects DNA methylation both during pluripotency and differentiation and plays a crucial, non-redundant role in cardiovascular specific differentiation and cardiomyocyte maturation. Our data elucidates important differences between ES and iPS HDAC1-KD cells that affect their ability to differentiate into cardiovascular lineages. As varying levels of chromatin modifying enzymes are likely to exist in patient derived iPS cells, understanding the molecular circuitry of these enzymes in ES and iPS cells is critical for their potential therapeutic applications in regenerative medicine. Further research in the molecular mechanisms involved in this process will greatly aid our understanding of the epigenetic circuitry of pluripotency and differentiation in pluripotent cells.

Investigation of the Stem Cells Used in Modeling Human Placental Trophoblast

2021 ◽  
Author(s):  
Lulu Ji ◽  
Lin Wang
Keyword(s):  
Stem Cells ◽  
Molecular Mechanisms ◽  
Embryonic Stem ◽  
Cell Lineage ◽  
Cell Types ◽  
Model Systems ◽  
Alternative Methods ◽  
Laboratory Animals ◽  
Placental Development ◽  
Induced Pluripotent

Human placenta is vital for fetal development, and act as an interface between the fetus and the expecting mother. Abnormal placentati on underpins various pregnancy complications such as miscarriage, pre-eclampsia and intrauterine growth restriction. Despite the important role of placenta, the molecular mechanisms governing placental formation and trophoblast cell lineage specification is poorly understand. It is mostly due to the lack of appropriate model system. The great various in placental types across mammals make it limit for the use of laboratory animals in studying human placental development. However, over the past few years, alternative methods have been employed, including human embryonic stem cells, induced pluripotent stem cells, human trophoblast stem cell, and 3-dimensional organoids. Herein, we summarize the present knowledge about human development, differentiated cell types in the trophoblast epithelium and current human placental trophoblast model systems.

scholarly journals Induced Pluripotent Stem Cells: Hope in the Treatment of Diseases, including Muscular Dystrophies

2020 ◽  
Vol 21 (15) ◽  
pp. 5467
Author(s):  
Daniela Gois Beghini ◽  
Samuel Iwao Horita ◽  
Cynthia Machado Cascabulho ◽  
Luiz Anastácio Alves ◽  
Andrea Henriques-Pons
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Embryonic Stem Cells ◽  
Embryonic Stem Cell ◽  
Embryonic Stem ◽  
Ips Cells ◽  
High Plasticity ◽  
Cell Based Therapy ◽  
Induced Pluripotent

Induced pluripotent stem (iPS) cells are laboratory-produced cells that combine the biological advantages of somatic adult and stem cells for cell-based therapy. The reprogramming of cells, such as fibroblasts, to an embryonic stem cell-like state is done by the ectopic expression of transcription factors responsible for generating embryonic stem cell properties. These primary factors are octamer-binding transcription factor 4 (Oct3/4), sex-determining region Y-box 2 (Sox2), Krüppel-like factor 4 (Klf4), and the proto-oncogene protein homolog of avian myelocytomatosis (c-Myc). The somatic cells can be easily obtained from the patient who will be subjected to cellular therapy and be reprogrammed to acquire the necessary high plasticity of embryonic stem cells. These cells have no ethical limitations involved, as in the case of embryonic stem cells, and display minimal immunological rejection risks after transplant. Currently, several clinical trials are in progress, most of them in phase I or II. Still, some inherent risks, such as chromosomal instability, insertional tumors, and teratoma formation, must be overcome to reach full clinical translation. However, with the clinical trials and extensive basic research studying the biology of these cells, a promising future for human cell-based therapies using iPS cells seems to be increasingly clear and close.

Targeted Gene Correction of Glanzmann Thrombasthenia Induced Pluripotent Stem Cells Restores Surface Expression and Fibrinogen Binding of Integrin αIIbβ3,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4173-4173
Author(s):  
Spencer Sullivan ◽  
Jason A. Mills ◽  
Li Zhai ◽  
Prasuna Paluru ◽  
Guohua Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Gene Therapy ◽  
Cell Lines ◽  
Surface Expression ◽  
Ips Cells ◽  
Ips Cell ◽  
Glanzmann Thrombasthenia ◽  
Integrin Αiibβ3 ◽  
Fibrinogen Binding ◽  
Induced Pluripotent

Abstract Abstract 4173 Glanzmann Thrombasthenia (GT) is a rare, autosomal recessive disorder resulting from an absence of functional platelet integrin αIIbβ3, leading to impaired platelet aggregation and clinically presenting with severe bleeding. It is a model of an inherited platelet disorder that might benefit from corrective gene therapy. Treatment options for GT are limited and largely supportive. They include anti-fibrinolytics, activated factor VII, platelet transfusions, and bone marrow transplantation. Recent gene therapy research in a canine model for GT demonstrated that lentiviral transduction of mobilized hematopoietic stem cells could restore 6% αIIbβ3 receptors in thrombasthenic canine platelets relative to wild type (WT) canine platelets. As an alternative gene therapy strategy, we generated induced pluripotent stem (iPS) cell lines from the peripheral blood of two patients with GT and examined whether a megakaryocyte-specific promoter driving αIIb cDNA expression within the AAVS1 safe harbor locus could ameliorate the GT phenotype in iPS cell-derived megakaryocytes. Patient 1 is a compound heterozygote for αIIb with the following two missense mutations: exon 2 c.331T>C (p.L100P) and exon 5 c.607G>A (p.S192N). Patient 2 is homozygous for a c.818G>A (p.G273D) mutation adjacent to the first calcium-binding domain of αIIb, leading to impaired intracellular transport of αIIbβ3. Both patients express <5% αIIbβ3 on the surface of their platelets. Peripheral blood mononuclear cells from both GT patients and WT controls were efficiently reprogrammed to pluripotency using a doxycycline-inducible polycistronic lentivirus containing OCT4, KLF4, SOX2, and CMYC. Transgene constructs using a murine GPIbα promoter driving either a green fluorescent protein (GFP) reporter or αIIb cDNA were inserted into a gene-targeting vector specific for the first intron of AAVS1, a locus amenable to gene targeting and resistant to transgene silencing in human iPS cells. The GPIbα-driven GFP transgene was efficiently targeted into AAVS1 in WT iPS cells using zinc finger nuclease-mediated homologous recombination, as was the αIIb construct into GT iPS cell lines. PCR and Southern blot analyses confirmed single, non-random, transgene integrations. The iPS cells were differentiated into megakaryocytes using a feeder-free/serum-free adherent monolayer protocol and analyzed by flow cytometry. GFP, along with endogenous CD41 (αIIb), was initially expressed in primitive WT hematopoietic progenitor cells. GFP expression was lost in erythrocytes and myeloid cells, but maintained in CD41+/CD42+ megakaryocytes, demonstrating that this transgenic construct mirrors endogenous CD41 expression. The GT phenotype was confirmed in megakaryocytes derived from patient iPS cells, showing loss of αIIbβ3 expression. When compared to WT iPS cell-derived megakaryocytes, gene-corrected GT iPS cell-derived megakaryocytes showed >50% and >70% αIIbβ3 surface expression for patients 1 and 2, respectively. Both patients' iPS cell-derived megakaryocytes also demonstrated fibrinogen binding upon thrombin activation. This is the first report of the generation and genetic correction of iPS cell lines from patients with a disease affecting platelet function. These findings suggest that this GPIbα-promoter construct targeted to the AAVS1 locus drives megakaryocyte-specific expression at a therapeutically significant level, which offers the possibility of correcting severe inherited platelet disorders beginning with iPS cells derived from these affected individuals. Disclosures: Lambert: Cangene: Honoraria.

scholarly journals Reprogramming of Mouse Calvarial Osteoblasts into Induced Pluripotent Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-11
Author(s):  
Yinxiang Wang ◽  
Jessica Aijia Liu ◽  
Keith K. H. Leung ◽  
Mai Har Sham ◽  
Danny Chan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Early Stage ◽  
Expression Profiles ◽  
Embryonic Stem ◽  
Gene Expression Profiles ◽  
Ips Cells ◽  
Egfp Expression ◽  
Retroviral Transduction ◽  
Intramembranous Bone ◽  
Induced Pluripotent

Previous studies have demonstrated the ability of reprogramming endochondral bone into induced pluripotent stem (iPS) cells, but whether similar phenomenon occurs in intramembranous bone remains to be determined. Here we adopted fluorescence-activated cell sorting-based strategy to isolate homogenous population of intramembranous calvarial osteoblasts from newborn transgenic mice carrying both Osx1-GFP::Cre and Oct4-EGFP transgenes. Following retroviral transduction of Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc), enriched population of osteoblasts underwent silencing of Osx1-GFP::Cre expression at early stage of reprogramming followed by late activation of Oct4-EGFP expression in the resulting iPS cells. These osteoblast-derived iPS cells exhibited gene expression profiles akin to embryonic stem cells and were pluripotent as demonstrated by their ability to form teratomas comprising tissues from all germ layers and also contribute to tail tissue in chimera embryos. These data demonstrate that iPS cells can be generated from intramembranous osteoblasts.

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