scholarly journals Induced pluripotent stem cells derived cardiomyocytes from Duchenne Muscular Dystrophy patients in vitro

2021 ◽  
Vol 37 (5) ◽  
Author(s):  
Fareeha Faizan Ghori ◽  
Mohsin Wahid
Keyword(s):  
Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Disease Modeling ◽  
Future Application ◽  
Induced Pluripotent

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.

scholarly journals Orai1–STIM1 Regulates Increased Ca2+ Mobilization, Leading to Contractile Duchenne Muscular Dystrophy Phenotypes in Patient-Derived Induced Pluripotent Stem Cells

Biomedicines ◽  
2021 ◽  
Vol 9 (11) ◽  
pp. 1589
Author(s):  
Tomoya Uchimura ◽  
Hidetoshi Sakurai
Keyword(s):  
Stem Cells ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Molecular Targets ◽  
Dystrophin Deficiency ◽  
Induced Pluripotent ◽  
Contractile Performance

Ca2+ overload is one of the factors leading to Duchenne muscular dystrophy (DMD) pathogenesis. However, the molecular targets of dystrophin deficiency-dependent Ca2+ overload and the correlation between Ca2+ overload and contractile DMD phenotypes in in vitro human models remain largely elusive. In this study, we utilized DMD patient-derived induced pluripotent stem cells (iPSCs) to differentiate myotubes using doxycycline-inducible MyoD overexpression, and searched for a target molecule that mediates dystrophin deficiency-dependent Ca2+ overload using commercially available chemicals and siRNAs. We found that several store-operated Ca2+ channel (SOC) inhibitors effectively prevented Ca2+ overload and identified that STIM1–Orai1 is a molecular target of SOCs. These findings were further confirmed by demonstrating that STIM1–Orai1 inhibitors, CM4620, AnCoA4, and GSK797A, prevented Ca2+ overload in dystrophic myotubes. Finally, we evaluated CM4620, AnCoA4, and GSK7975A activities using a previously reported model recapitulating a muscle fatigue-like decline in contractile performance in DMD. All three chemicals ameliorated the decline in contractile performance, indicating that modulating STIM1–Orai1-mediated Ca2+ overload is effective in rescuing contractile phenotypes. In conclusion, SOCs are major contributors to dystrophin deficiency-dependent Ca2+ overload through STIM1–Orai1 as molecular mediators. Modulating STIM1–Orai1 activity was effective in ameliorating the decline in contractile performance in DMD.

scholarly journals Questionnaire for evaluating information, knowledge, and attitudes on donation, storage, and application of induced pluripotent stem cells

Genetika ◽  
2021 ◽  
Vol 53 (2) ◽  
pp. 813-823
Author(s):  
Sanja Rascanin ◽  
Mirjana Jovanovic ◽  
Dejan Stevanovic ◽  
Nemanja Rancic
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Disease Modeling ◽  
Ethical Issues ◽  
Embryonic Stem ◽  
Knowledge And Attitudes ◽  
Induced Pluripotent

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.

scholarly journals Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening

2021 ◽  
Vol 22 (15) ◽  
pp. 8227
Author(s):  
Mattia Pasqua ◽  
Roberto Di Gesù ◽  
Cinzia Maria Chinnici ◽  
Pier Giulio Conaldi ◽  
Maria Giovanna Francipane
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Disease Modeling ◽  
Rapid Screening ◽  
Drug Candidates ◽  
Open Questions ◽  
Induced Pluripotent

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.

scholarly journals The Promise of Human Induced Pluripotent Stem Cells in Dental Research

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Thekkeparambil Chandrabose Srijaya ◽  
Padmaja Jayaprasad Pradeep ◽  
Rosnah Binti Zain ◽  
Sabri Musa ◽  
Noor Hayaty Abu Kasim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Patient Specific ◽  
Dental Research ◽  
Cell Based Therapy ◽  
Induced Pluripotent ◽  
Disease Specific

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.

scholarly journals Generation of star-shaped human induced astrocytes with a mature inflammatory phenotype for CNS disease modeling

2021 ◽  
Author(s):  
Dimitrios Voulgaris ◽  
Polyxeni Nikolakopoulou ◽  
Anna Herland
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Glutamate Transporter ◽  
Cns Disease ◽  
Human Neural Stem Cells ◽  
Induced Pluripotent ◽  
Prolonged Differentiation

Generating astrocytes from induced pluripotent stem cells has been hampered by either prolonged differentiation -spanning over two months -or by shorter protocols that generate immature astrocytes, devoid of salient inflammation-associated astrocytic traits pivotal for CNS neuropathological modeling. We directed human neural stem cells derived from induced pluripotent stem cells to astrocytic commitment and maturity by orchestrating an astrocytic-tuned culturing environment. In under 28 days, the generated cells express canonical and mature astrocytic markers, denoted by the expression of AQP4 and, remarkably, the expression and functionality of glutamate transporter EAAT2. We also show that this protocol generates astrocytes that encompass traits critical in CNS disease modeling, such as glutathione synthesis and secretion, upregulation of ICAM-1 and a cytokine secretion profile which is on par with primary astrocytes. This protocol generates a multifaceted astrocytic model suitable for CNS in vitro disease modeling and personalized medicine through brain-on-chip technologies.

scholarly journals Versatility of Induced Pluripotent Stem Cells (iPSCs) for Improving the Knowledge on Musculoskeletal Diseases

2020 ◽  
Vol 21 (17) ◽  
pp. 6124
Author(s):  
Clara Sanjurjo-Rodríguez ◽  
Rocío Castro-Viñuelas ◽  
María Piñeiro-Ramil ◽  
Silvia Rodríguez-Fernández ◽  
Isaac Fuentes-Boquete ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Musculoskeletal Diseases ◽  
The Body ◽  
Cellular Mechanisms ◽  
Induced Pluripotent ◽  
New Strategies

Induced pluripotent stem cells (iPSCs) represent an unlimited source of pluripotent cells capable of differentiating into any cell type of the body. Several studies have demonstrated the valuable use of iPSCs as a tool for studying the molecular and cellular mechanisms underlying disorders affecting bone, cartilage and muscle, as well as their potential for tissue repair. Musculoskeletal diseases are one of the major causes of disability worldwide and impose an important socio-economic burden. To date there is neither cure nor proven approach for effectively treating most of these conditions and therefore new strategies involving the use of cells have been increasingly investigated in the recent years. Nevertheless, some limitations related to the safety and differentiation protocols among others remain, which humpers the translational application of these strategies. Nonetheless, the potential is indisputable and iPSCs are likely to be a source of different types of cells useful in the musculoskeletal field, for either disease modeling or regenerative medicine. In this review, we aim to illustrate the great potential of iPSCs by summarizing and discussing the in vitro tissue regeneration preclinical studies that have been carried out in the musculoskeletal field by using iPSCs.

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