scholarly journals Reprogramming with Small Molecules instead of Exogenous Transcription Factors

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Tongxiang Lin ◽  
Shouhai Wu
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Mouse Embryonic Fibroblast ◽  
Patient Specific ◽  
Full Potential ◽  
Ipsc Generation ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) could be employed in the creation of patient-specific stem cells, which could subsequently be used in various basic and clinical applications. However, current iPSC methodologies present significant hidden risks with respect to genetic mutations and abnormal expression which are a barrier in realizing the full potential of iPSCs. A chemical approach is thought to be a promising strategy for safety and efficiency of iPSC generation. Many small molecules have been identified that can be used in place of exogenous transcription factors and significantly improve iPSC reprogramming efficiency and quality. Recent studies have shown that the use of small molecules results in the generation of chemically induced pluripotent stem cells from mouse embryonic fibroblast cells. These studies might lead to new areas of stem cell research and medical applications, not only human iPSC by chemicals alone, but also safe generation of somatic stem cells for cell based clinical trials and other researches. In this paper, we have reviewed the recent advances in small molecule approaches for the generation of iPSCs.

scholarly journals Generation of induced pluripotent stem cells from human blood

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5476-5479 ◽  
Author(s):  
Yuin-Han Loh ◽  
Suneet Agarwal ◽  
In-Hyun Park ◽  
Achia Urbach ◽  
Hongguang Huo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Human Blood ◽  
Pluripotent Stem Cells ◽  
Methylation Status ◽  
Embryonic Stem ◽  
Dermal Fibroblasts ◽  
Patient Specific ◽  
Induced Pluripotent

Human dermal fibroblasts obtained by skin biopsy can be reprogrammed directly to pluripotency by the ectopic expression of defined transcription factors. Here, we describe the derivation of induced pluripotent stem cells from CD34+ mobilized human peripheral blood cells using retroviral transduction of OCT4/SOX2/KLF4/MYC. Blood-derived human induced pluripotent stem cells are indistinguishable from human embryonic stem cells with respect to morphology, expression of surface antigens, and pluripotency-associated transcription factors, DNA methylation status at pluripotent cell-specific genes, and the capacity to differentiate in vitro and in teratomas. The ability to reprogram cells from human blood will allow the generation of patient-specific stem cells for diseases in which the disease-causing somatic mutations are restricted to cells of the hematopoietic lineage.

scholarly journals Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

2017 ◽  
Author(s):  
Adekunle Ebenezer Omole ◽  
Adegbenro Omotuyi John Fakoya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Molecular Mechanism ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Patient Specific ◽  
Induced Pluripotent

The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogrammed human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers of reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSCs generation. Distinct barriers and enhancers of reprogramming have been elucidated and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSCs field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and regenerative medicine. Additionally, this study appraised the role of genomic editing technology in the generation of healthy iPSCs.

scholarly journals Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

2017 ◽  
Author(s):  
Adekunle Ebenezer Omole ◽  
Adegbenro Omotuyi John Fakoya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Molecular Mechanism ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Patient Specific ◽  
Induced Pluripotent

The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogrammed human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers of reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSCs generation. Distinct barriers and enhancers of reprogramming have been elucidated and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSCs field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and regenerative medicine. Additionally, this study appraised the role of genomic editing technology in the generation of healthy iPSCs.

scholarly journals Ten years of progress and promise of induced pluripotent stem cells: historical origins, characteristics, mechanisms, limitations, and potential applications

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4370 ◽  
Author(s):  
Adekunle Ebenezer Omole ◽  
Adegbenro Omotuyi John Fakoya
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Transcription Factors ◽  
Induced Pluripotent Stem Cells ◽  
Molecular Mechanism ◽  
Pluripotent Stem Cells ◽  
Ectopic Expression ◽  
Embryonic Stem ◽  
Patient Specific ◽  
Induced Pluripotent

The discovery of induced pluripotent stem cells (iPSCs) by Shinya Yamanaka in 2006 was heralded as a major breakthrough of the decade in stem cell research. The ability to reprogram human somatic cells to a pluripotent embryonic stem cell-like state through the ectopic expression of a combination of embryonic transcription factors was greeted with great excitement by scientists and bioethicists. The reprogramming technology offers the opportunity to generate patient-specific stem cells for modeling human diseases, drug development and screening, and individualized regenerative cell therapy. However, fundamental questions have been raised regarding the molecular mechanism of iPSCs generation, a process still poorly understood by scientists. The efficiency of reprogramming of iPSCs remains low due to the effect of various barriers to reprogramming. There is also the risk of chromosomal instability and oncogenic transformation associated with the use of viral vectors, such as retrovirus and lentivirus, which deliver the reprogramming transcription factors by integration in the host cell genome. These challenges can hinder the therapeutic prospects and promise of iPSCs and their clinical applications. Consequently, extensive studies have been done to elucidate the molecular mechanism of reprogramming and novel strategies have been identified which help to improve the efficiency of reprogramming methods and overcome the safety concerns linked with iPSC generation. Distinct barriers and enhancers of reprogramming have been elucidated, and non-integrating reprogramming methods have been reported. Here, we summarize the progress and the recent advances that have been made over the last 10 years in the iPSC field, with emphasis on the molecular mechanism of reprogramming, strategies to improve the efficiency of reprogramming, characteristics and limitations of iPSCs, and the progress made in the applications of iPSCs in the field of disease modelling, drug discovery and regenerative medicine. Additionally, this study appraises the role of genomic editing technology in the generation of healthy iPSCs.

scholarly journals Small Molecules Greatly Improve Conversion of Human-Induced Pluripotent Stem Cells to the Neuronal Lineage

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sally K. Mak ◽  
Y. Anne Huang ◽  
Shifteh Iranmanesh ◽  
Malini Vangipuram ◽  
Ramya Sundararajan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Neuronal Differentiation ◽  
Pluripotent Stem Cells ◽  
Patient Specific ◽  
Specific Cell ◽  
Neuronal Marker ◽  
Neural Lineage ◽  
Induced Pluripotent

Efficientin vitrodifferentiation into specific cell types is more important than ever after the breakthrough in nuclear reprogramming of somatic cells and its potential for disease modeling and drug screening. Key success factors for neuronal differentiation are the yield of desired neuronal marker expression, reproducibility, length, and cost. Three main neuronal differentiation approaches are stromal-induced neuronal differentiation, embryoid body (EB) differentiation, and direct neuronal differentiation. Here, we describe our neurodifferentiation protocol using small molecules that very efficiently promote neural induction in a 5-stage EB protocol from six induced pluripotent stem cells (iPSC) lines from patients with Parkinson’s disease and controls. This protocol generates neural precursors using Dorsomorphin and SB431542 and further maturation into dopaminergic neurons by replacing sonic hedgehog with purmorphamine or smoothened agonist. The advantage of this approach is that all patient-specific iPSC lines tested in this study were successfully and consistently coaxed into the neural lineage.

scholarly journals Selected small molecules as inductors of pluripotent stem cells

2017 ◽  
Vol 63 (4) ◽  
Author(s):  
Małgorzata Baranek ◽  
Wojciech T Markiewicz ◽  
Jan Barciszewski
Keyword(s):  
Stem Cells ◽  
Regenerative Medicine ◽  
Nucleic Acids ◽  
Small Molecules ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
General Idea ◽  
Patient Specific ◽  
General Character ◽  
Induced Pluripotent

The general idea of regenerative medicine is to fix or replace tissues or organs with alive and patient-specific implants. Pluripotent stem cells are capable of indefinite self-renewal and differentiation into all cell types of body with origin from the three germ layers of the developing embryo, therefore they have a potential to play a substantial role in regenerative medicine. Easily accessible source of induced pluripotent stem cells may allow obtaining and culturing tissues in vitro. Many improvements in the methods leading to obtain such cells have been made by various research groups in order to limit immunogenicity and tumorigenesis, increase efficiency and accelerate kinetics. One of the approaches affecting pluripotency is usage of small molecule compounds including RNA-derivatives – nucleosides analogues. It would be great to assess general character of such molecules and reveal their new derivatives or modifications to improve induced pluripotent stem cells (iPSCs) reprogramming efficiency. Understanding the epigenetic changes during cellular reprogramming will extend understanding of stem cell biology and lead to potential therapeutic approaches. In this digest of compounds found in literature as proven or putative inductors of cells’ reprogramming to pluripotency there are compounds that may substitute for transgenic nucleic acids delivery in order to improve time and efficiency of reprogramming. Nucleic acids’ derivatives or modifications of particular atoms or substitutes influence modulating activities of small molecules, especially their inhibiting activity.  Due to dosage-dependent effect of small molecules influence on genes, their application concentration needs to be strictly determined.

scholarly journals Myocardial Reprogramming Medicine: The Development, Application, and Challenge of Induced Pluripotent Stem Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-22
Author(s):  
Yigang Wang
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Patient Specific ◽  
Somatic Cell Reprogramming ◽  
Potential Applications ◽  
Ipsc Generation ◽  
Cardiovascular Cells ◽  
Induced Pluripotent

Induced pluripotent stem cells (iPSCs) can be generated by reprogramming of adult/somatic cells. The somatic cell reprogramming technology offers a promising strategy for patient-specific cardiac regenerative medicine, disease modeling, and drug discovery. iPSCs are an ideal potential option for an autologous cell source, as compared to other stem/progenitor cells, because they can be propagated indefinitely and are able to generate a large number of functional cardiovascular cells. However, there are concerns about the specificity, efficiency, immunogenicity, and safety of iPSCs which are major challenges in current translational studies. In order to bring iPSC technology closer to clinical use, fundamental changes in this technique are required to ensure that therapeutic progenies are functional and nontumorigenic. It is therefore critical to understand and investigate the biology, genetic, and epigenetic mechanisms of iPSCs generation and differentiation. In this spotlight paper the discovery, history, and relative mechanisms of iPSC generation are summarized. The current technological improvements and potential applications are highlighted along with the important challenges and perspectives. Finally, emerging technologies are presented in which improvements to iPSC generation and differentiation approaches might warrant further investigation, such as integration-free approaches, direct reprogramming, and the development of iPSC banking.

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