scholarly journals MicroRNAs and Induced Pluripotent Stem Cells for Human Disease Mouse Modeling

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Chingiz Underbayev ◽  
Siddha Kasar ◽  
Yao Yuan ◽  
Elizabeth Raveche

Human disease animal models are absolutely invaluable tools for our understanding of mechanisms involved in both physiological and pathological processes. By studying various genetic abnormalities in these organisms we can get a better insight into potential candidate genes responsible for human disease development. To this point a mouse represents one of the most used and convenient species for human disease modeling. Hundreds if not thousands of inbred, congenic, and transgenic mouse models have been created and are now extensively utilized in the research labs worldwide. Importantly, pluripotent stem cells play a significant role in developing new genetically engineered mice with the desired human disease-like phenotype. Induced pluripotent stem (iPS) cells which represent reprogramming of somatic cells into pluripotent stem cells represent a significant advancement in research armament. The novel application of microRNA manipulation both in the generation of iPS cells and subsequent lineage-directed differentiation is discussed. Potential applications of induced pluripotent stem cell—a relatively new type of pluripotent stem cells—for human disease modeling by employing human iPS cells derived from normal and diseased somatic cells and iPS cells derived from mouse models of human disease may lead to uncovering of disease mechanisms and novel therapies.

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Ji-feng Kang ◽  
Bei-sha Tang ◽  
Ji-feng Guo

In recent years, induced pluripotent stem cells (iPSCs) were widely used for investigating the mechanisms of Parkinson’s disease (PD). Somatic cells from patients withSNCA(α-synuclein),LRRK2(leucine-rich repeat kinase 2),PINK1(PTEN induced putative kinase 1),Parkinmutations, and at-risk individuals carryingGBA(β-glucocerebrosidase) mutations have been successfully induced to iPSCs and subsequently differentiated into dopaminergic (DA) neurons. Importantly, some PD-related cell phenotypes, includingα-synuclein aggregation, mitophagy, damaged mitochondrial DNA, and mitochondrial dysfunction, have been described in these iPSCs models, which further investigated the pathogenesis of PD. In 2007, Takahashi et al. and Vodyanik et al. generated iPSCs from human somatic cells for the first time. Since then, patients derived iPSCs were applied for disease modeling, drug discovery and screening, autologous cell replacement therapy, and other biological applications. iPSC research has now become a hot topic in a wide range of fields. This review summarizes the recent progress of PD patients derived iPSC models in pathogenic mechanism investigation and potential clinical applications, especially their promising strategy in pharmacological study and DA neurons transplantation therapy. However, the challenges of iPSC transplantation still exist, and it has a long way to go before it can be used in clinical application.


2020 ◽  
Author(s):  
Immacolata Belviso ◽  
Veronica Romano ◽  
Daria Nurzynska ◽  
Clotilde Castaldo ◽  
Franca Di Meglio

Induced Pluripotent Stem cells (iPSC) are adult somatic cells genetically reprogrammed to an embryonic stem cell-like state. Due to their autologous origin from adult somatic cells, iPSCs are considered a tremendously valuable tool for regenerative medicine, disease modeling, drug discovery and testing. iPSCs were first obtained by introducing specific transcription factors through retroviral transfection. However, cell reprogramming obtained by integrating methods prevent clinical application of iPSC because of potential risk for infection, teratomas and genomic instability. Therefore, several integration-free alternate methods have been developed and tested thus far to overcome safety issues. The present chapter provides an overview and a critical analysis of advantages and disadvantages of non-integrating methods used to generate iPSCs.


2011 ◽  
Vol 366 (1575) ◽  
pp. 2198-2207 ◽  
Author(s):  
Keisuke Okita ◽  
Shinya Yamanaka

Somatic cells have been reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors, such as Oct3/4 , Sox2 , Klf4 and c-Myc . Induced pluripotent stem (iPS) cells from a patient's somatic cells could be a useful source for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as retrovirus and lentivirus, which integrate the reprogramming factors into the host genomes and may increase the risk of tumour formation. Several non-integration methods have been reported to overcome the safety concern associated with the generation of iPS cells, such as transient expression of the reprogramming factors using adenovirus vectors or plasmids, and direct delivery of reprogramming proteins. Although these transient expression methods could avoid genomic alteration of iPS cells, they are inefficient. Several studies of gene expression, epigenetic modification and differentiation revealed the insufficient reprogramming of iPS cells, thus suggesting the need for improvement of the reprogramming procedure not only in quantity but also in quality. This report will summarize the current knowledge of iPS generation and discuss future reprogramming methods for medical application.


2016 ◽  
Vol 17 (2) ◽  
pp. 256 ◽  
Author(s):  
Mohammed Kawser Hossain ◽  
Ahmed Abdal Dayem ◽  
Jihae Han ◽  
Subbroto Kumar Saha ◽  
Gwang-Mo Yang ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thekkeparambil Chandrabose Srijaya ◽  
Padmaja Jayaprasad Pradeep ◽  
Rosnah Binti Zain ◽  
Sabri Musa ◽  
Noor Hayaty Abu Kasim ◽  
...  

Induced pluripotent stem cell-based therapy for treating genetic disorders has become an interesting field of research in recent years. However, there is a paucity of information regarding the applicability of induced pluripotent stem cells in dental research. Recent advances in the use of induced pluripotent stem cells have the potential for developing disease-specific iPSC linesin vitrofrom patients. Indeed, this has provided a perfect cell source for disease modeling and a better understanding of genetic aberrations, pathogenicity, and drug screening. In this paper, we will summarize the recent progress of the disease-specific iPSC development for various human diseases and try to evaluate the possibility of application of iPS technology in dentistry, including its capacity for reprogramming some genetic orodental diseases. In addition to the easy availability and suitability of dental stem cells, the approach of generating patient-specific pluripotent stem cells will undoubtedly benefit patients suffering from orodental disorders.


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