scholarly journals Stem cells, organoids, and organ-on-a-chip models for personalized in vitro drug testing

2021 ◽  
Vol 28 ◽  
pp. 7-14
Author(s):  
Damiën van Berlo ◽  
Vivian V.T. Nguyen ◽  
Vasiliki Gkouzioti ◽  
Kirsten Leineweber ◽  
Marianne C. Verhaar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Testing ◽  
Organ On A Chip

Stem cells and organs-on-chips: new promising technologies for human infertility treatment

2021 ◽  
Author(s):  
Eisa Tahmasbpour Marzouni ◽  
Andrew Henrik Sinclair ◽  
Catharyn Stern ◽  
Elena Jane Tucker
Keyword(s):  
Stem Cells ◽  
Primordial Germ Cell ◽  
Reproductive Failure ◽  
Human Reproduction ◽  
Patient Specific ◽  
Sex Development ◽  
Organ On A Chip ◽  
Induced Pluripotent ◽  
Infertile Patients

Abstract Having biological children remains an unattainable dream for most couples with reproductive failure or gonadal dysgenesis. The combination of stem cells with gene editing technology and organ-on-a-chip models provides unique opportunity for infertile patients with impaired gametogenesis caused by congenital disorders in sex development or cancer survivors. But, how will these technologies overcome human infertility? This review discusses the regenerative mechanisms, applications and advantages of different types of stem cells for restoring gametogenesis in infertile patients, as well as major challenges that must be overcome prior to clinical application. The importance and limitations of in vitro generation of gametes from patient-specific human induced pluripotent stem cells (hiPSCs) will be discussed in the context of human reproduction. The potential role of organ-on-a-chip models that can direct differentiation of hiPSCs-derived primordial germ cell-like cells to gametes and other reproductive organoids is also explored. These rapidly evolving technologies provide future prospects for improving fertility to individuals and couples who experience reproductive failure.

scholarly journals Patient-specific hepatocyte-like cells derived from induced pluripotent stem cells model pazopanib-mediated hepatotoxicity

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Yukti Choudhury ◽  
Yi Chin Toh ◽  
Jiangwa Xing ◽  
Yinghua Qu ◽  
Jonathan Poh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Kinase Inhibitor ◽  
Patient Specific ◽  
Drug Induced ◽  
Clinical Phenotypes ◽  
Induced Pluripotent

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.

scholarly journals Human Pluripotent Stem Cell-Derived Cardiomyocytes as Research and Therapeutic Tools

2014 ◽  
Vol 2014 ◽  
pp. 1-14 ◽  
Author(s):  
Ivana Acimovic ◽  
Aleksandra Vilotic ◽  
Martin Pesl ◽  
Alain Lacampagne ◽  
Petr Dvorak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Pluripotent Stem Cells ◽  
Drug Testing ◽  
Embryonic Stem ◽  
Cell Types ◽  
Patient Specific ◽  
Disease Modelling ◽  
Therapeutic Tools ◽  
Induced Pluripotent

Human pluripotent stem cells (hPSCs), namely, embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), with their ability of indefinite self-renewal and capability to differentiate into cell types derivatives of all three germ layers, represent a powerful research tool in developmental biology, for drug screening, disease modelling, and potentially cell replacement therapy. Efficient differentiation protocols that would result in the cell type of our interest are needed for maximal exploitation of these cells. In the present work, we aim at focusing on the protocols for differentiation of hPSCs into functional cardiomyocytesin vitroas well as achievements in the heart disease modelling and drug testing on the patient-specific iPSC-derived cardiomyocytes (iPSC-CMs).

Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine

2021 ◽  
Vol 28 ◽  
Author(s):  
Sanjeev Gautam ◽  
Sangita Biswas ◽  
Birbal Singh ◽  
Ying Guo ◽  
Peng Deng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Testing ◽  
Diagnostic Tools ◽  
Cell Therapies ◽  
Non Invasive ◽  
Key Issues ◽  
Induced Pluripotent

: There is a momentous surge in the development of stem cell technology as a therapeutic and diagnostic tools. Stem cell-derived cells are currently used in various clinical trials. However, key issues and challenges involve the low differentiation efficiency, integration, and functioning of transplanted stem cells-derived cells. Extraction of bone marrow, adipose, or other mesenchymal stem cells (MSCs) involves invasive methods, specialized skills, and expensive technologies. Urine-derived cells, on the other hand, are obtained by non-invasive methods. Samples can be obtained repeatedly from patients of any age. Urine-derived cells are used to generate reprogrammed or induced pluripotent stem cells (iPSCs), which can be cultured, and differentiated into various types of cell lineages for biomedical investigations and drug testing in vitro or in vivo using model animals of human diseases. Urine cell-derived iPSCs (UiPSCs) have emerged as a major area of research and immense therapeutic significance. Given that preliminary preclinical studies are successful in terms of safety and as a regenerative tool, the UiPSCs will pave the way to develop and expedite various types of autologous stem cell therapies.

scholarly journals Generation of functional heart organoids from mouse embryonic stem cells.

2020 ◽  
Author(s):  
Jiyoung Lee ◽  
Fumitoshi Ishino ◽  
Akito Sutani ◽  
Rin Kaneko
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Drug Testing ◽  
Embryonic Stem ◽  
Mouse Embryonic Stem Cell ◽  
Embryoid Bodies ◽  
Fibroblast Growth ◽  
Spatiotemporal Regulation

Abstract For the understanding of the spatiotemporal regulation of cardiogenesis, it is important to generate in vitro model of hearts. This protocol introduces how to generate heart organoids from mouse embryonic stem cell-derived embryoid bodies (EB) in the presence of the laminin-entactin (LN/ET) complex and fibroblast growth factor 4 (FGF4) by three consecutive steps, 1) the culture of ESCs, 2) in vitro differentiation of ESCs into EBs and 3) in vitro culture of EBs for the generation of heart organoids. The generated heart organoids possess structural and functional capacity similar to atrial and ventricular parts of in vivo embryonic heart. This simplified protocol also provides a promising research tool with a broad range of applications, including drug testing.

scholarly journals Bioengineered tooth emulation systems for regenerative and pharmacological purposes

2021 ◽  
Vol 41 ◽  
pp. 502-516
Author(s):  
P Pagella ◽  
◽  
A Cordiale ◽  
GD Marconi ◽  
O Trubiani ◽  
...  
Keyword(s):  
Stem Cells ◽  
Drug Testing ◽  
Periodontal Diseases ◽  
Human Tooth ◽  
Dental Tissues ◽  
Carious Lesions ◽  
Bioengineered Tooth ◽  
Different Populations ◽  
Regenerative Therapies

Genetic conditions, traumatic injuries, carious lesions and periodontal diseases are all responsible for dental pathologies. The current clinical approaches are based on the substitution of damaged dental tissues with inert materials, which, however, do not ensure full physiological recovery of the teeth. Different populations of dental mesenchymal stem cells have been isolated from dental tissues and several attempts have already been made at using these stem cells for the regeneration of human dental tissues. Despite encouraging progresses, dental regenerative therapies are very far from any clinical applications. This is tightly connected with the absence of proper platforms that would model and faithfully mimic human dental tissues in their complexity. Therefore, in the last decades, many efforts have been dedicated for the development of innovative systems capable of emulating human tooth physiology in vitro. This review focuses on the use of in vitro culture systems, such as bioreactors and “organ-on-a-chip” microfluidic devices, for the modelling of human dental tissues and their potential use for dental regeneration and drug testing.

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.

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