scholarly journals Optimizing Differentiation Protocols for Producing Dopaminergic Neurons from Human Induced Pluripotent Stem Cells for Tissue Engineering Applications

2015 ◽  
Vol 10s1 ◽  
pp. BMI.S20064 ◽  
Author(s):  
Meghan Robinson ◽  
Suk-yu Yau ◽  
Lin Sun ◽  
Nicole Gabers ◽  
Emma Bibault ◽  
...  

Parkinson's disease (PD) is a neurodegenerative disorder that results when the dopaminergic neurons (DNs) present in the substantia nigra necessary for voluntary motor control are depleted, making patients with this disorder ideal candidates for cell replacement therapy. Human induced pluripotent stem cells (hiPSCs), obtained by reprogramming adult cells, possess the properties of pluripotency and immortality while enabling the possibility of patient-specific therapies. An effective cell therapy for PD requires an efficient, defined method of DN generation, as well as protection from the neuroinflammatory environment upon engraftment. Although similar in pluripotency to human embryonic stem cells (hESCs), hiPSCs differentiate less efficiently into neuronal subtypes. Previous work has shown that treatment with guggulsterone can efficiently differentiate hESCs into DNs. Our work shows that guggulsterone is able to derive DNs from hiPSCs with comparable efficiency, and furthermore, this differentiation can be achieved inside three-dimensional fibrin scaffolds that could enhance cell survival upon engraftment.

2016 ◽  
Vol 52 (2) ◽  
pp. 123-136
Author(s):  
Ewelina Augustyniak ◽  
Katarzyna Kulcenty ◽  
Michał Lach ◽  
Igor Piotrowski ◽  
Wiktoria Maria Suchorska

The application of stem cells (SCs) in regenerative medicine has recently become a rapidly growing field, holding promise for combating a number of currently incurable disorders: including diabetes, neurodegenerative, retinal and cardiac diseases, as well as muscular dystrophy. The search for alternative approaches led to the development of human induced pluripotent stem cells (hiPSCs) which have unrestricted proliferative activity and pluripotency – the capacity to differentiation into derivatives of three germ layers (meso-, ecto – and endoderm). Because hiPSCs are developed from adult human cells throughout the forced expression of pluripotency factors, they are free from the ethical concerns associated with human embryonic stem cells (hESCs), that creation involves the destruction of human embryos. Moreover, the use of hiPSCs contributes to the development of personalized medicine that exploits patient-specific cells extremely useful in autologous grafts. In the present study the methods of hiPSCs differentiation into stem cell-derived neurons, cardiomyocytes, chondrocytes and osteocytes were summarized and evaluated having regard to their most important aspects.


Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5476-5479 ◽  
Author(s):  
Yuin-Han Loh ◽  
Suneet Agarwal ◽  
In-Hyun Park ◽  
Achia Urbach ◽  
Hongguang Huo ◽  
...  

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.


2011 ◽  
Vol 268-270 ◽  
pp. 835-837
Author(s):  
De Wu Liu ◽  
Yong Tie Li ◽  
De Ming Liu ◽  
Pu Ning

Human induced pluripotent stem cells is promising for regenerative medicine and tissue engineering. In this chapter, we focus on the culture and characteristics of human induced pluripotent stem cells. The induced pluripotent stem cells were plated on murine embryonic fibroblast feeder cells and expanded in human embryonic stem cells media contained basic fibroblast growth factor. The cells were passaged by collagenase IV digestion method and observed under invert microscope. The expression of alkaline phosphatase was detected by immunocytochemistry. The cultured induced pluripotent stem cells grew well and stability with similar characteristics of human embryonic stem cells. These cells also expressed alkaline phosphatase. They formed embryoid body in feeder-free and suspension culture conditions. The results provide an experimental basis for improvement of induction study and further application to generate patient-specific induced pluripotent stem cells.


2017 ◽  
Author(s):  
Adekunle Ebenezer Omole ◽  
Adegbenro Omotuyi John Fakoya

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.


2017 ◽  
Author(s):  
Adekunle Ebenezer Omole ◽  
Adegbenro Omotuyi John Fakoya

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.


PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4370 ◽  
Author(s):  
Adekunle Ebenezer Omole ◽  
Adegbenro Omotuyi John Fakoya

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.


2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Wenbin Wan ◽  
Lan Cao ◽  
Bill Kalionis ◽  
Shijin Xia ◽  
Xiantao Tai

Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons. Incurable neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) show dramatic rising trends particularly in the advanced age groups. However, the underlying mechanisms are not yet fully elucidated, and to date there are no biomarkers for early detection or effective treatments for the underlying causes of these diseases. Furthermore, due to species variation and differences between animal models (e.g., mouse transgenic and knockout models) of neurodegenerative diseases, substantial debate focuses on whether animal and cell culture disease models can correctly model the condition in human patients. In 2006, Yamanaka of Kyoto University first demonstrated a novel approach for the preparation of induced pluripotent stem cells (iPSCs), which displayed similar pluripotency potential to embryonic stem cells (ESCs). Currently, iPSCs studies are permeating many sectors of disease research. Patient sample-derived iPSCs can be used to construct patient-specific disease models to elucidate the pathogenic mechanisms of disease development and to test new therapeutic strategies. Accordingly, the present review will focus on recent progress in iPSC research in the modeling of neurodegenerative disorders and in the development of novel therapeutic options.


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