scholarly journals Induced Pluripotent Stem Cells in Cardiovascular Medicine

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Toru Egashira ◽  
Shinsuke Yuasa ◽  
Keiichi Fukuda
Keyword(s):  
Regenerative Medicine ◽  
Embryonic Stem ◽  
Stem Cell Differentiation ◽  
Ips Cells ◽  
Cardiovascular Research ◽  
Ips Cell ◽  
Cell Technology ◽  
The Future ◽  
Human Ips Cells ◽  
Induced Pluripotent

Induced pluripotent stem (iPS) cells are generated by reprogramming human somatic cells through the forced expression of several embryonic stem (ES) cell-specific transcription factors. The potential of iPS cells is having a significant impact on regenerative medicine, with the promise of infinite self-renewal, differentiation into multiple cell types, and no problems concerning ethics or immunological rejection. Human iPS cells are currently generated by transgene introduction principally through viral vectors, which integrate into host genomes, although the associated risk of tumorigenesis is driving research into nonintegration methods. Techniques for pluripotent stem cell differentiation and purification to yield cardiomyocytes are also advancing constantly. Although there remain some unsolved problems, cardiomyocyte transplantation may be a reality in the future. After those problems will be solved, applications of human iPS cells in human cardiovascular regenerative medicine will be envisaged for the future. Furthermore, iPS cell technology has generated new human disease models using disease-specific cells. This paper summarizes the progress of iPS cell technology in cardiovascular research.

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.

Generation of Blood Cells from Human Ips Cells in Vitro through the Hematopoietic Progenitors Concentrated within the Unique Structures, Ips-Sac.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1992-1992 ◽  
Author(s):  
Naoya Takayama ◽  
Koji Eto ◽  
Hiromitsu Nakauchi ◽  
Shinya Yamanaka
Keyword(s):  
Cell Lines ◽  
Blood Cells ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Dermal Fibroblasts ◽  
Hematopoietic Progenitors ◽  
Transfusion Therapy ◽  
Ips Cell ◽  
Human Ips Cells

Abstract Human embryonic stem cells (hESCs) are proposed as an alternative source for transfusion therapy or studies of hematopoiesis. We have recently established an in vitro culture system whereby hESCs can be differentiated into hematopoietic progenitors within the ‘unique sac-like structures’ (ES-sacs), that are able to produce megakaryocytes and platelets (Takayama et al., Blood, 111, 5298–306, 2008). However there is a little concern that repetitive transfusion with same human ESC-derived platelets may induce immunological rejection against transfused platelets expressing allogenic HLA. Meanwhile, induced pluripotent stem (iPS) cells established from donor with identical HLA are well known as a potential and given source on platelet transfusion devoid of rejection. To examine if human iPS cells could generate platelets as well as from hESCs, we utilized 3 different human iPS cell lines; two were induced by transduction of 4 genes (Oct3/4, Klf4, Sox2, and c-Myc) in adult dermal fibroblasts, and one was by 3 genes without c-Myc. Sac-like structures (iPS-sac), inducible from 3 iPS cell lines, concentrated hematopoietic progenitors that expressed early hemato-endothelial markers, such as CD34, CD31, CD41a (integrin αIIb) and CD45. These progenitors were able to form hematopoietic colonies in semi-solid culture and differentiate into several blood cells including leukocytes, erythrocytes or platelets. Of these, obtained platelets responded to agonist stimulation, in which the function was as much as human ESC-derived platelets, as evidenced by PAC-1 binding with activated αIIbβ3 integrin or full spreading onto fibrinogen. These results collectively indicated that human dermal fibroblasts could generate functional and mature hematopoietic cells through the reprogramming process and this method may be useful for basic studies of hematopoietic disorders and clinical therapy in the future.

scholarly journals Future perspective of induced pluripotent stem cells for diagnosis, drug screening and treatment of human diseases

2010 ◽  
Vol 104 (07) ◽  
pp. 39-44 ◽  
Author(s):  
Qizhou Lian ◽  
Yenyen Chow ◽  
Miguel Esteban ◽  
Duanqing Pei ◽  
Hung-Fat Tse
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Regenerative Medicine ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Cell Biology ◽  
Stem Cell Biology ◽  
Ips Cell ◽  
Cell Technology ◽  
Induced Pluripotent

SummaryRecent advances in stem cell biology have transformed the understanding of cell physiology and developmental biology such that it can now play a more prominent role in the clinical application of stem cell and regenerative medicine. Success in the generation of human induced pluripotent stem cells (iPS) as well as related emerging technology on the iPS platform provide great promise in the development of regenerative medicine. Human iPS cells show almost identical properties to human embryonic stem cells (ESC) in pluripotency, but avoid many of their limitations of use. In addition, investigations into reprogramming of somatic cells to pluripotent stem cells facilitate a deeper understanding of human stem cell biology. The iPS cell technology has offered a unique platform for studying the pathogenesis of human disease, pharmacological and toxicological testing, and cell-based therapy. Nevertheless, significant challenges remain to be overcome before the promise of human iPS cell technology can be realised.

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 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.

scholarly journals ProspectiveIn VitroModels of Channelopathies and Cardiomyopathies

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Nanako Kawaguchi ◽  
Emiko Hayama ◽  
Yoshiyuki Furutani ◽  
Toshio Nakanishi
Keyword(s):  
Heart Disease ◽  
Regenerative Medicine ◽  
Expression Profiles ◽  
Disease Model ◽  
Ips Cells ◽  
Micro Rna ◽  
Rna Expression ◽  
Ips Cell ◽  
Induced Pluripotent

Anin vitroheart disease model is a promising model used for identifying the genes responsible for the disease, evaluating the effects of drugs, and regenerative medicine. We were interested in disease models using a patient-induced pluripotent stem (iPS) cell-derived cardiomyocytes because of their similarity to a patient’s tissues. However, as these studies have just begun, we would like to review the literature in this and other related fields and discuss the path for future models of molecular biology that can help to diagnose and cure diseases, and its involvement in regenerative medicine. The heterogeneity of iPS cells and/or differentiated cardiomyocytes has been recognized as a problem. Anin vitroheart disease model should be evaluated using molecular biological analyses, such as mRNA and micro-RNA expression profiles and proteomic analysis.

Human Embryonic Stem Cell-Specific Micrornas Promote Full Programming of Induced Pluripotent Stem Cells Derived From CD34+ Cord Blood Cells Stored Frozen for More Than 20 Years.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2622-2622
Author(s):  
Man Ryul Lee ◽  
Nutan Prasain ◽  
Young-June Kim ◽  
Mervin C. Yoder ◽  
Hal E. Broxmeyer
Keyword(s):  
Transcription Factors ◽  
Cord Blood ◽  
Production Efficiency ◽  
Embryonic Stem ◽  
Ips Cells ◽  
Self Renewal ◽  
Ips Cell ◽  
Cd34 Cells ◽  
Induced Pluripotent ◽  
Hes Cells

Abstract Abstract 2622 Numerous somatic cells can be reprogrammed by ectopic expression of defined transcription factors including OCT4, SOX2, MYC, KLF4 (Yamanaka's factors), NANOG, and LIN28 to pluripotent cells, referred to as induced pluripotent stem (iPS) cells which can then be differentiated into a variety of somatic cell types. Production efficiency of iPS cells by these transcription factors is extremely low, and therefore a large portion of the cells remain unprogrammed or incompletely reprogrammed. Thus, identification of additional factors required for enhancing iPS cells production efficiency has been an intensive research subject. We generated iPS cell from CD34+ cells of human umbilical cord blood that had been frozen in an unseparated state for twenty plus years using lentiviruses expressing Yamanaka's factors. During the iPS cell production processes, we monitored cell surface expression of TRA1-60, a marker for human embryonic stem (hES) cells, within colonies using a live cell staining method. Three to four weeks after gene transduction, TRA1-60 positive cells emerged in about 5% of the colonies. So, we mechanically separated TRA1-60 negative cells from TRA1-60 positive cells in colonies. Further culture did not allow TRA1-60 negative cells to convert to TRA1-60 positive cells even after 10 passages, indicating that TRA1-60 negative cells were stable at an incompletely reprogrammed state. TRA1-60 negative cells were similar to hES cells in morphology and still demonstrated expression of exogenous Yamanaka's factors. TRA1-60 negative cells were distinct from TRA1-60 positive cells with regards to methylation pattern of OCT4 promoter regions and differentiation potential. In contrast to TRA1-60 positive cells, incompletely reprogrammed TRA1-60 negative cells lacked hESC-specific miRNAs (miR-302 and 371 clusters), which are known to be involved in controlling self-renewal and pluripotency of hES cells. We hypothesized that these miRNAs can promote a transition from incompletely to fully reprogrammed iPS cells. To test this hypothesis, we introduced the miRNA clusters of miR-302 and 371 using lentiviruses to TRA1-60 negative incompletely reprogrammed cell to determine whether these miRNAs could convert TRA-60 negative cells to TRA1-60 positive completely reprogrammed cells. Our results showed that these miRNAs were able to convert more than 10% of TRA1-60 negative incompletely reprogrammed cells to TRA1-60 positive iPS cells with characteristics of completely reprogrammed iPS cells, such as differentiation of three germ layers and acquisition of typical hES cell-specific cell cycling patterns with an unrestricted G1 to S phase transition. These results indicate that hES-specific miRNAs have a strong potential to promote partially reprogrammed cord blood CD34+ cells to iPS cells with extensive self-renewal capacity. Our study suggests that current techniques with low iPS cell production efficiency can be improved by ectopic overexpression of hES-specific miRNAs (miR-302 and371 clusters). Disclosures: Broxmeyer: Corduse: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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 Machine Learning Approach to Automated Quality Identification of Human Induced Pluripotent Stem Cell Colony Images

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Henry Joutsijoki ◽  
Markus Haponen ◽  
Jyrki Rasku ◽  
Katriina Aalto-Setälä ◽  
Martti Juhola
Keyword(s):  
Machine Learning ◽  
Stem Cell ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Support Vector ◽  
Ips Cell ◽  
Cell Technology ◽  
Induced Pluripotent

The focus of this research is on automated identification of the quality of human induced pluripotent stem cell (iPSC) colony images. iPS cell technology is a contemporary method by which the patient’s cells are reprogrammed back to stem cells and are differentiated to any cell type wanted. iPS cell technology will be used in future to patient specific drug screening, disease modeling, and tissue repairing, for instance. However, there are technical challenges before iPS cell technology can be used in practice and one of them is quality control of growing iPSC colonies which is currently done manually but is unfeasible solution in large-scale cultures. The monitoring problem returns to image analysis and classification problem. In this paper, we tackle this problem using machine learning methods such as multiclass Support Vector Machines and several baseline methods together with Scaled Invariant Feature Transformation based features. We perform over 80 test arrangements and do a thorough parameter value search. The best accuracy (62.4%) for classification was obtained by using ak-NN classifier showing improved accuracy compared to earlier studies.

scholarly journals Bone Morphogenetic Protein 4 (BMP4) Enhances the Differentiation of Human Induced Pluripotent Stem Cells into Limbal Progenitor Cells

2021 ◽  
Vol 43 (3) ◽  
pp. 2124-2134
Author(s):  
Hyun Soo Lee ◽  
Jeewon Mok ◽  
Choun-Ki Joo
Keyword(s):  
Progenitor Cells ◽  
Dermal Fibroblast ◽  
Ips Cells ◽  
Human Dermal Fibroblast ◽  
Corneal Epithelial ◽  
Specific Medium ◽  
Morphogenetic Protein ◽  
Human Ips Cells ◽  
Limbal Stem Cell ◽  
Induced Pluripotent

Corneal epithelium maintains visual acuity and is regenerated by the proliferation and differentiation of limbal progenitor cells. Transplantation of human limbal progenitor cells could restore the integrity and functionality of the corneal surface in patients with limbal stem cell deficiency. However, multiple protocols are employed to differentiate human induced pluripotent stem (iPS) cells into corneal epithelium or limbal progenitor cells. The aim of this study was to optimize a protocol that uses bone morphogenetic protein 4 (BMP4) and limbal cell-specific medium. Human dermal fibroblast-derived iPS cells were differentiated into limbal progenitor cells using limbal cell-specific (PI) medium and varying doses (1, 10, and 50 ng/mL) and durations (1, 3, and 10 days) of BMP4 treatment. Differentiated human iPS cells were analyzed by real-time polymerase chain reaction (RT-PCR), Western blotting, and immunocytochemical studies at 2 or 4 weeks after BMP4 treatment. Culturing human dermal fibroblast-derived iPS cells in limbal cell-specific medium and BMP4 gave rise to limbal progenitor and corneal epithelial-like cells. The optimal protocol of 10 ng/mL and three days of BMP4 treatment elicited significantly higher limbal progenitor marker (ABCG2, ∆Np63α) expression and less corneal epithelial cell marker (CK3, CK12) expression than the other combinations of BMP4 dose and duration. In conclusion, this study identified a successful reprogramming strategy to induce limbal progenitor cells from human iPS cells using limbal cell-specific medium and BMP4. Additionally, our experiments indicate that the optimal BMP4 dose and duration favor limbal progenitor cell differentiation over corneal epithelial cells and maintain the phenotype of limbal stem cells. These findings contribute to the development of therapies for limbal stem cell deficiency disorders.

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