scholarly journals Nanomedicine-based Curcumin Approach Improved ROS Damage in Best Dystrophy-specific Induced Pluripotent Stem Cells

2019 ◽  
Vol 28 (11) ◽  
pp. 1345-1357 ◽  
Author(s):  
Tai-Chi Lin ◽  
Yi-Ying Lin ◽  
Chih-Chen Hsu ◽  
Yi-Ping Yang ◽  
Chang-Hao Yang ◽  
...  

Best dystrophy (BD), also termed best vitelliform macular dystrophy (BVMD), is a juvenile-onset form of macular degeneration and can cause central visual loss. Unfortunately, there is no clear definite therapy for BD or improving the visual function on this progressive disease. The human induced pluripotent stem cell (iPSC) system has been recently applied as an effective tool for genetic consultation and chemical drug screening. In this study, we developed patient-specific induced pluripotent stem cells (BD-iPSCs) from BD patient-derived dental pulp stromal cells and then differentiated BD-iPSCs into retinal pigment epithelial cells (BD-RPEs). BD-RPEs were used as an expandable platform for in vitro candidate drug screening. Compared with unaffected sibling-derived iPSC-derived RPE cells (Ctrl-RPEs), BD-RPEs exhibited typical RPE-specific markers with a lower expression of the tight junction protein ZO-1 and Bestrophin-1 (BEST1), as well as reduced phagocytic capabilities. Notably, among all candidate drugs, curcumin was the most effective for upregulating both the BEST1 and ZO-1 genes in BD-RPEs. Using the iPSC-based drug-screening platform, we further found that curcumin can significantly improve the mRNA expression levels of Best gene in BD-iPSC-derived RPEs. Importantly, we demonstrated that curcumin-loaded PLGA nanoparticles (Cur-NPs) were efficiently internalized by BD-RPEs. The Cur-NPs-based controlled release formulation further increased the expression of ZO-1 and Bestrophin-1, and promoted the function of phagocytosis and voltage-dependent calcium channels in BD-iPSC-derived RPEs. We further demonstrated that Cur-NPs enhanced the expression of antioxidant enzymes with a decrease in intracellular ROS production and hydrogen peroxide-induced oxidative stress. Collectively, these data supported that Cur-NPs provide a potential cytoprotective effect by regulating the anti-oxidative abilities of degenerated RPEs. In addition, the application of patient-specific iPSCs provides an effective platform for drug screening and personalized medicine in incurable diseases.

Cardiology ◽  
2015 ◽  
Vol 131 (4) ◽  
pp. 236-244 ◽  
Author(s):  
Hong-jie Chi ◽  
Song Gao ◽  
Xin-chun Yang ◽  
Jun Cai ◽  
Wen-shu Zhao ◽  
...  

Induced pluripotent stem cells (iPSCs) are generated by reprogramming human somatic cells through the overexpression of four transcription factors: Oct4, Sox2, Klf4 and c-Myc. iPSCs are capable of indefinite self-renewal, and they can differentiate into almost any type of cell in the body. These cells therefore offer a highly valuable therapeutic strategy for tissue repair and regeneration. Recent experimental and preclinical research has revealed their potential for cardiovascular disease diagnosis, drug screening and cellular replacement therapy. Nevertheless, significant challenges remain in terms of the development and clinical application of human iPSCs. Here, we review current progress in research related to patient-specific iPSCs for ex vivo modeling of cardiovascular disorders and drug screening, and explore the potential of human iPSCs for use in the field of cardiovascular regenerative medicine.


Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3250
Author(s):  
Ponthip Pratumkaew ◽  
Surapol Issaragrisil ◽  
Sudjit Luanpitpong

The breakthrough in human induced pluripotent stem cells (hiPSCs) has revolutionized the field of biomedical and pharmaceutical research and opened up vast opportunities for drug discovery and regenerative medicine, especially when combined with gene-editing technology. Numerous healthy and patient-derived hiPSCs for human disease modeling have been established, enabling mechanistic studies of pathogenesis, platforms for preclinical drug screening, and the development of novel therapeutic targets/approaches. Additionally, hiPSCs hold great promise for cell-based therapy, serving as an attractive cell source for generating stem/progenitor cells or functional differentiated cells for degenerative diseases, due to their unlimited proliferative capacity, pluripotency, and ethical acceptability. In this review, we provide an overview of hiPSCs and their utility in the study of hematologic disorders through hematopoietic differentiation. We highlight recent hereditary and acquired genetic hematologic disease modeling with patient-specific iPSCs, and discuss their applications as instrumental drug screening tools. The clinical applications of hiPSCs in cell-based therapy, including the next-generation cancer immunotherapy, are provided. Lastly, we discuss the current challenges that need to be addressed to fulfill the validity of hiPSC-based disease modeling and future perspectives of hiPSCs in the field of hematology.


2013 ◽  
Vol 5 (188) ◽  
pp. 188le2-188le2 ◽  
Author(s):  
B. Bilican ◽  
A. Serio ◽  
S. J. Barmada ◽  
A. L. Nishimura ◽  
G. J. Sullivan ◽  
...  

2012 ◽  
Vol 4 (145) ◽  
pp. 145ra104-145ra104 ◽  
Author(s):  
N. Egawa ◽  
S. Kitaoka ◽  
K. Tsukita ◽  
M. Naitoh ◽  
K. Takahashi ◽  
...  

2013 ◽  
Vol 5 (188) ◽  
pp. 188lr2-188lr2 ◽  
Author(s):  
N. Egawa ◽  
S. Kitaoka ◽  
K. Tsukita ◽  
M. Naitoh ◽  
K. Takahashi ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-15 ◽  
Author(s):  
Methichit Wattanapanitch

Over the past decade, enormous progress has been made in the field of induced pluripotent stem cells (iPSCs). Patients’ somatic cells such as skin fibroblasts or blood cells can be used to generate disease-specific pluripotent stem cells, which have unlimited proliferation and can differentiate into all cell types of the body. Human iPSCs offer great promises and opportunities for treatments of degenerative diseases and studying disease pathology and drug screening. So far, many iPSC-derived disease models have led to the discovery of novel pathological mechanisms as well as new drugs in the pipeline that have been tested in the iPSC-derived cells for efficacy and potential toxicities. Furthermore, recent advances in genome editing technology in combination with the iPSC technology have provided a versatile platform for studying stem cell biology and regenerative medicine. In this review, an overview of iPSCs, patient-specific iPSCs for disease modeling and drug screening, applications of iPSCs and genome editing technology in hematological disorders, remaining challenges, and future perspectives of iPSCs in hematological diseases will be discussed.


Sign in / Sign up

Export Citation Format

Share Document