scholarly journals Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing

2017 ◽  
Vol 23 (7) ◽  
pp. 878-884 ◽  
Author(s):  
Miguel Crespo ◽  
Eduardo Vilar ◽  
Su-Yi Tsai ◽  
Kyle Chang ◽  
Sadaf Amin ◽  
...  
2018 ◽  
Vol 24 (4) ◽  
pp. 526-526
Author(s):  
Miguel Crespo ◽  
Eduardo Vilar ◽  
Su-Yi Tsai ◽  
Kyle Chang ◽  
Sadaf Amin ◽  
...  

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yukti Choudhury ◽  
Yi Chin Toh ◽  
Jiangwa Xing ◽  
Yinghua Qu ◽  
Jonathan Poh ◽  
...  

Abstract Idiosyncratic drug-induced hepatotoxicity is a major cause of liver damage and drug pipeline failure, and is difficult to study as patient-specific features are not readily incorporated in traditional hepatotoxicity testing approaches using population pooled cell sources. Here we demonstrate the use of patient-specific hepatocyte-like cells (HLCs) derived from induced pluripotent stem cells for modeling idiosyncratic hepatotoxicity to pazopanib (PZ), a tyrosine kinase inhibitor drug associated with significant hepatotoxicity of unknown mechanistic basis. In vitro cytotoxicity assays confirmed that HLCs from patients with clinically identified hepatotoxicity were more sensitive to PZ-induced toxicity than other individuals, while a prototype hepatotoxin acetaminophen was similarly toxic to all HLCs studied. Transcriptional analyses showed that PZ induces oxidative stress (OS) in HLCs in general, but in HLCs from susceptible individuals, PZ causes relative disruption of iron metabolism and higher burden of OS. Our study establishes the first patient-specific HLC-based platform for idiosyncratic hepatotoxicity testing, incorporating multiple potential causative factors and permitting the correlation of transcriptomic and cellular responses to clinical phenotypes. Establishment of patient-specific HLCs with clinical phenotypes representing population variations will be valuable for pharmaceutical drug testing.


Genetika ◽  
2021 ◽  
Vol 53 (2) ◽  
pp. 813-823
Author(s):  
Sanja Rascanin ◽  
Mirjana Jovanovic ◽  
Dejan Stevanovic ◽  
Nemanja Rancic

The discovery of Induced Pluripotent Stem Cells (iPSCs) opened the possibilities for reprogramming adult somatic cells back to a pluripotent state in vitro by inducing a forced expression of specific transcription factors. Thus, iPSCs might have potential application in regenerative medicine, transplantation, avoidance of tissue rejection, disease modeling, and drug testing. Because of apparent ethical issues connected with donation and derivation of biomaterials, iPSCs are considered as a research alternative to ethically highly disputed Embryonic Stem Cells (ESCs). Objective: The aim of this paper was to describe the development of a questionnaire for evaluating information, knowledge, and attitudes on donation, storage, and application of iPSCs (i.e., the QIPSC). We performed a prospective qualitative study based on the development, validation and reliability testing of the QIPSC. The study included 122 respondents and the final version of the QIPSC with 34 items. The reliability analysis for part of information and knowledge of respondents according to iPSCs was then performed with the questions included in this two-component model and obtained a Cronbach's alpha value of 0.783 and 0.870, respectively. It has been shown that the range of correct answers to questions in part of knowledge of respondents according to iPSCs was from 17.2-63.1%. The results of our study show that the QIPSC was a unique, reliable, and valid questionnaire for assessing the level of information, knowledge, and attitudes on donation, storage, and application of iPSCs.


2021 ◽  
Vol 37 (5) ◽  
Author(s):  
Fareeha Faizan Ghori ◽  
Mohsin Wahid

Objective: This study aimed at the in vitro generation of DMD-cardiomyocytes from patient-specific induced pluripotent stem cells derived from a Pakistani patient for future work on DMD in vitro disease modeling and drug testing for efficacy and toxicity. Methods: This in vitro experimental study was carried out from December 2018 to January 2019 at Stem Cells and Regenerative Medicine Lab (SCRML) at Dow Research Institute of Biotechnology and Biomedical Sciences (DRIBBS), Dow University of Health Sciences (DUHS) Urine derived DMD-iPSCs were used which had been generated previously from a Pakistani DMD patient who had been selected through non-random purposive sampling. These were differentiated towards cardiomyocytes using Cardiomyocytes Differentiation media having specified growth factors and then the molecular characterization of the differentiated cells was done using immunofluorescence. Results: Pakistani patient’s DMD-Cardiomyocytes were generated and their identity was confirmed by positive immunofluorescence for the expression of cardiac markers NKX2-5 and TNNT-2. Conclusion: This study aimed for in vitro generation of DMD cardiomyocytes for future application in disease modeling, new drug testing for efficacy and toxicity, as well as for drug-testing for tailored personalized therapy. To the best of our knowledge, this was the first time DMD-Cardiomyocytes were generated from Pakistani DMD patients using their own induced pluripotent stem cells. doi: https://doi.org/10.12669/pjms.37.5.3104 How to cite this:Ghori FF, Wahid M. Induced pluripotent stem cells derived cardiomyocytes from Duchenne Muscular Dystrophy patients in vitro. Pak J Med Sci. 2021;37(5):---------. doi: https://doi.org/10.12669/pjms.37.5.3104 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


2021 ◽  
Author(s):  
Shimpei Maruoka ◽  
Toshiyasu Ojima ◽  
Hiromitsu Iwamoto ◽  
Junya Kitadani ◽  
Hirotaka Tabata ◽  
...  

Abstract Significant efficacy of induced pluripotent stem cells (iPSCs) in generating DCs for cancer vaccine therapy was suggested in our previous studies. In clinical application of DC vaccine therapy, however, few DC vaccine systems have shown strong clinical response. To enhance immunogenicity in the DC vaccine, we transfected patient-derived iPSDCs with in vitro transcriptional RNA (ivtRNA), which was obtained from tumors of three patients with colorectal cancer.We investigated iPSDCs-ivtRNA which were induced by transfecting ivtRNA obtained from tumors of three colorectal cancer patients, and examined its antitumor effect. Moreover, we analyzed neoantigens expressed in colorectal cancer cells and examined whether iPSDCs-ivtRNA induced cytotoxic T lymphocytes (CTLs) against the predicted neoantigens.CTLs activated by iPSDCs-ivtRNA exhibited cytotoxic activity against the tumor spheroids in all three patients with colorectal cancer. Whole-exome sequencing revealed 1251 nonsynonymous mutations and 2155 neoantigens (IC50 <500 nM) were predicted. For IFN-γ ELISPOT assay, these candidate neoantigens were further prioritised and 12 candidates were synthesized. IFN-γ ELISPOT assay revealed that the CTLs induced by iPSDCs-ivtRNA responded to one of the candidate neoantigens.In vitro CTLs obtained by transfecting tumor-derived RNA into iPSDCs derived from three patients with colorectal cancer showed potent tumor-specific killing effect.


2011 ◽  
Vol 20 (24) ◽  
pp. 4851-4864 ◽  
Author(s):  
Hsiang-Po Huang ◽  
Pin-Hsun Chen ◽  
Wuh-Liang Hwu ◽  
Ching-Yu Chuang ◽  
Yin-Hsiu Chien ◽  
...  

2021 ◽  
Vol 22 (15) ◽  
pp. 8227
Author(s):  
Mattia Pasqua ◽  
Roberto Di Gesù ◽  
Cinzia Maria Chinnici ◽  
Pier Giulio Conaldi ◽  
Maria Giovanna Francipane

The possibility to reproduce key tissue functions in vitro from induced pluripotent stem cells (iPSCs) is offering an incredible opportunity to gain better insight into biological mechanisms underlying development and disease, and a tool for the rapid screening of drug candidates. This review attempts to summarize recent strategies for specification of iPSCs towards hepatobiliary lineages —hepatocytes and cholangiocytes— and their use as platforms for disease modeling and drug testing. The application of different tissue-engineering methods to promote accurate and reliable readouts is discussed. Space is given to open questions, including to what extent these novel systems can be informative. Potential pathways for improvement are finally suggested.


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