Self-filling microwell arrays (SFMAs) for tumor spheroid formation

Lab on a Chip ◽  
2018 ◽  
Vol 18 (22) ◽  
pp. 3516-3528 ◽  
Author(s):  
Amir Seyfoori ◽  
Ehsan Samiei ◽  
Neda Jalili ◽  
Brent Godau ◽  
Mehdi Rahmanian ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Great Promise ◽  
Tumor Spheroid ◽  
Spheroid Formation ◽  
Tumor Spheroids

Self-filling microwell arrays hold great promise for the production of 3D tumor spheroids and organoids for disease modeling and drug discovery.

scholarly journals High Folic Acid Supplementation Reprograms Glycolytic and Lactate-generating Metabolism to Promote Anchorage-independent Tumor Spheroid Formation in NSCLC Cells (P05-001-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yi-Wen Chen ◽  
Rwei-Fen S Huang
Keyword(s):  
Folic Acid ◽  
Protein Expression ◽  
Glucose Transporter ◽  
Cell Protein ◽  
Control Group ◽  
Tumor Spheroid ◽  
Related Protein ◽  
Spheroid Formation ◽  
Tumor Spheroids ◽  
Glucose Transporter 1

Abstract Objectives Aims of this study were to investigate the effect of HF on anchorage-independent tumor spheroid formation and its’ working mechanisms of lung malignant tumor cells. Methods Human NSCLC cells A549 were cultured in control (C) medium (2.2 μM folic acid) or HF medium (10, 30, 50 μM folic acid) for 4 days. Cells were harvested to explore the self-renewal capacity of cancer cells by observing the anchorage-independent tumor spheroid formation. Meanwhile, the L-lactate assay were conducted to evaluate the lactate-generating state and the cell protein extract for the western blotting analysis to realize expression of energy metabolism related proteins in cells. Results The results showed that numbers of tumor spheroids in HF group were significantly higher than the control group. Besides, compared to C group, HF50 group showed significantly reduced lactate release into medium with highly accumulation in cellular lactate levels. The glycolytic-related protein expression of hexokinase II (HKII), lactate dehydrogenase (LDH) were increased and glucose transporter 1 (GLUT1), pyruvate dehydrogenase (PDH) were decreased in HF group. The signaling-related protein expression of insulin receptor substract-1 (IRS-1), hypoxia-inducible factor-1 alpha (HIF-1α) were increased and PI3 kinase (PI3K), AMP-activated protein kinase (AMPK) were decreased in HF group. Conclusions Collectively, HF supplementation may reprogram glycolytic metabolism and increase anchorage-independent tumor spheroids formation to mediate malignant progress of NSCLC. Funding Sources Ministry of Science and Technology, Taiwan, R.O.C.

Mixed hydrogel bead-based tumor spheroid formation and anticancer drug testing

The Analyst ◽  
2014 ◽  
Vol 139 (10) ◽  
pp. 2449-2458 ◽  
Author(s):  
Yaolei Wang ◽  
Jinyi Wang
Keyword(s):  
Anticancer Drug ◽  
Drug Testing ◽  
Tumor Spheroid ◽  
Spheroid Formation ◽  
Tumor Spheroids ◽  
Hydrogel Bead ◽  
Hydrogel Beads

A microfluidic method was developed for the formation of tumor spheroids using alginate and matrigel mixed hydrogel beads.

scholarly journals Emerging hiPSC Models for Drug Discovery in Neurodegenerative Diseases

2021 ◽  
Vol 22 (15) ◽  
pp. 8196
Author(s):  
Dorit Trudler ◽  
Swagata Ghatak ◽  
Stuart A. Lipton
Keyword(s):  
Drug Discovery ◽  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Neural Function ◽  
Neural Cells ◽  
Human Samples ◽  
Healthy Donors ◽  
Induced Pluripotent

Neurodegenerative diseases affect millions of people worldwide and are characterized by the chronic and progressive deterioration of neural function. Neurodegenerative diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), represent a huge social and economic burden due to increasing prevalence in our aging society, severity of symptoms, and lack of effective disease-modifying therapies. This lack of effective treatments is partly due to a lack of reliable models. Modeling neurodegenerative diseases is difficult because of poor access to human samples (restricted in general to postmortem tissue) and limited knowledge of disease mechanisms in a human context. Animal models play an instrumental role in understanding these diseases but fail to comprehensively represent the full extent of disease due to critical differences between humans and other mammals. The advent of human-induced pluripotent stem cell (hiPSC) technology presents an advantageous system that complements animal models of neurodegenerative diseases. Coupled with advances in gene-editing technologies, hiPSC-derived neural cells from patients and healthy donors now allow disease modeling using human samples that can be used for drug discovery.

scholarly journals Recent Advances in Disease Modeling and Drug Discovery for Diabetes Mellitus Using Induced Pluripotent Stem Cells

2016 ◽  
Vol 17 (2) ◽  
pp. 256 ◽  
Author(s):  
Mohammed Kawser Hossain ◽  
Ahmed Abdal Dayem ◽  
Jihae Han ◽  
Subbroto Kumar Saha ◽  
Gwang-Mo Yang ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cells ◽  
Drug Discovery ◽  
Induced Pluripotent Stem Cells ◽  
Pluripotent Stem Cells ◽  
Disease Modeling ◽  
Recent Advances ◽  
Induced Pluripotent

scholarly journals NRF2 is required for structural and metabolic maturation of human induced pluripotent stem cell-derived ardiomyocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xinyuan Zhang ◽  
Liang Ye ◽  
Hao Xu ◽  
Qin Zhou ◽  
Bin Tan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Oxidative Phosphorylation ◽  
Pluripotent Stem Cell ◽  
Disease Modeling ◽  
Induced Pluripotent Stem Cell ◽  
Metabolic Energy ◽  
Cell Maturation ◽  
Great Promise ◽  
Functional Changes ◽  
Induced Pluripotent

Abstract Background Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold great promise for regenerative medicine and in drugs screening. Despite displaying key cardiomyocyte phenotypic characteristics, they more closely resemble fetal/neonatal cardiomyocytes and are still immature; these cells mainly rely on glucose as a substrate for metabolic energy, while mature cardiomyocytes mainly employ oxidative phosphorylation of fatty acids. Studies showed that the alteration of metabolism pattern from glycolysis to oxidative phosphorylation improve the maturity of hiPSC-CMs. As a transcription factor, accumulating evidences showed the important role of NRF2 in the regulation of energy metabolism, which directly regulates the expression of mitochondrial respiratory complexes. Therefore, we hypothesized that NRF2 is involved in the maturation of hiPSC-CMs. Methods The morphological and functional changes related to mitochondria and cell maturation were analyzed by knock-down and activation of NRF2. Results The results showed that the inhibition of NRF2 led to the retardation of cell maturation. The activation of NRF2 leads to a more mature hiPSC-CMs phenotype, as indicated by the increase of cardiac maturation markers, sarcomere length, calcium transient dynamics, the number and fusion events of mitochondria, and mitochondrial respiration. Bioinformatics analysis showed that in addition to metabolism-related genes, NRF2 also activates the expression of myocardial ion channels. Conclusions These findings indicated that NRF2 plays an important role in the maturation of hiPSC-CMs. The present work provides greater insights into the molecular regulation of hiPSC-CMs metabolism and theoretical basis in drug screening, disease modeling, and alternative treatment.

Fabrication of PNIPAm-based Thermoresponsive hydrogel microwell arrays for tumor spheroid formation

2021 ◽  
pp. 112100
Author(s):  
Dinesh Dhamecha ◽  
Duong Le ◽  
Tomali Chakravarty ◽  
Kalindu Perera ◽  
Arnob Dutta ◽  
...  
Keyword(s):  
Tumor Spheroid ◽  
Spheroid Formation ◽  
Thermoresponsive Hydrogel

scholarly journals Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery

2021 ◽  
Vol 22 (3) ◽  
pp. 1203
Author(s):  
Lu Qian ◽  
Julia TCW
Keyword(s):  
Drug Discovery ◽  
Disease Modeling ◽  
Three Dimensional ◽  
Structural Complexity ◽  
Induced Pluripotent Stem Cell ◽  
Cell Types ◽  
Central Nerve System ◽  
Human Ipscs ◽  
Nerve System

A high-throughput drug screen identifies potentially promising therapeutics for clinical trials. However, limitations that persist in current disease modeling with limited physiological relevancy of human patients skew drug responses, hamper translation of clinical efficacy, and contribute to high clinical attritions. The emergence of induced pluripotent stem cell (iPSC) technology revolutionizes the paradigm of drug discovery. In particular, iPSC-based three-dimensional (3D) tissue engineering that appears as a promising vehicle of in vitro disease modeling provides more sophisticated tissue architectures and micro-environmental cues than a traditional two-dimensional (2D) culture. Here we discuss 3D based organoids/spheroids that construct the advanced modeling with evolved structural complexity, which propels drug discovery by exhibiting more human specific and diverse pathologies that are not perceived in 2D or animal models. We will then focus on various central nerve system (CNS) disease modeling using human iPSCs, leading to uncovering disease pathogenesis that guides the development of therapeutic strategies. Finally, we will address new opportunities of iPSC-assisted drug discovery with multi-disciplinary approaches from bioengineering to Omics technology. Despite technological challenges, iPSC-derived cytoarchitectures through interactions of diverse cell types mimic patients’ CNS and serve as a platform for therapeutic development and personalized precision medicine.

scholarly journals Matrigel Mattress

2015 ◽  
Vol 117 (12) ◽  
pp. 995-1000 ◽  
Author(s):  
Tromondae K. Feaster ◽  
Adrian G. Cadar ◽  
Lili Wang ◽  
Charles H. Williams ◽  
Young Wook Chun ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Single Cell ◽  
Troponin I ◽  
Disease Modeling ◽  
Sodium Current ◽  
Culture Method ◽  
Adult Rabbit ◽  
Standard Equipment ◽  
Cell Contractility ◽  
Contractile Performance

Rationale: The lack of measurable single-cell contractility of human-induced pluripotent stem cell–derived cardiac myocytes (hiPSC-CMs) currently limits the utility of hiPSC-CMs for evaluating contractile performance for both basic research and drug discovery. Objective: To develop a culture method that rapidly generates contracting single hiPSC-CMs and allows quantification of cell shortening with standard equipment used for studying adult CMs. Methods and Results: Single hiPSC-CMs were cultured for 5 to 7 days on a 0.4- to 0.8-mm thick mattress of undiluted Matrigel (mattress hiPSC-CMs) and compared with hiPSC-CMs maintained on a control substrate (<0.1-mm thick 1:60 diluted Matrigel, control hiPSC-CMs). Compared with control hiPSC-CMs, mattress hiPSC-CMs had more rod-shape morphology and significantly increased sarcomere length. Contractile parameters of mattress hiPSC-CMs measured with video-based edge detection were comparable with those of freshly isolated adult rabbit ventricular CMs. Morphological and contractile properties of mattress hiPSC-CMs were consistent across cryopreserved hiPSC-CMs generated independently at another institution. Unlike control hiPSC-CMs, mattress hiPSC-CMs display robust contractile responses to positive inotropic agents, such as myofilament calcium sensitizers. Mattress hiPSC-CMs exhibit molecular changes that include increased expression of the maturation marker cardiac troponin I and significantly increased action potential upstroke velocity because of a 2-fold increase in sodium current ( I Na ). Conclusions: The Matrigel mattress method enables the rapid generation of robustly contracting hiPSC-CMs and enhances maturation. This new method allows quantification of contractile performance at the single-cell level, which should be valuable to disease modeling, drug discovery, and preclinical cardiotoxicity testing.

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