3D Bioprinting of Anatomically Realistic Tissue Constructs for Disease Modeling and Drug Testing

2021 ◽  
Author(s):  
Nicanor I. Moldovan
Keyword(s):  
Drug Testing ◽  
Disease Modeling ◽  
3D Bioprinting ◽  
Tissue Constructs

scholarly journals Rapid 3D BioPrinting of a human iPSC-derived cardiac micro-tissue for high-throughput drug testing

2021 ◽  
Vol 3 ◽  
pp. 100007
Author(s):  
Kathleen L. Miller ◽  
Yi Xiang ◽  
Claire Yu ◽  
Jacob Pustelnik ◽  
Jerry Wu ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Testing ◽  
3D Bioprinting ◽  
Human Ipsc

scholarly journals Engineered heart tissue models from hiPSC-derived cardiomyocytes and cardiac ECM for disease modeling and drug testing applications

2019 ◽  
Vol 92 ◽  
pp. 145-159 ◽  
Author(s):  
Idit Goldfracht ◽  
Yael Efraim ◽  
Rami Shinnawi ◽  
Ekaterina Kovalev ◽  
Irit Huber ◽  
...  
Keyword(s):  
Drug Testing ◽  
Disease Modeling ◽  
Heart Tissue ◽  
Engineered Heart Tissue ◽  
Tissue Models

scholarly journals 3D bioprinting: novel approaches for engineering complex human tissue equivalents and drug testing

2021 ◽  
Author(s):  
Judith Hagenbuchner ◽  
Daniel Nothdurfter ◽  
Michael J. Ausserlechner
Keyword(s):  
Human Tissue ◽  
Intracellular Signaling ◽  
Mammalian Cells ◽  
Drug Testing ◽  
Patient Specific ◽  
Attractive Alternative ◽  
3D Bioprinting ◽  
Tissue Equivalents ◽  
Common Strategy ◽  
Specific Tissue

Abstract Conventional approaches in drug development involve testing on 2D-cultured mammalian cells, followed by experiments in rodents. Although this is the common strategy, it has significant drawbacks: in 2D cell culture with human cells, the cultivation at normoxic conditions on a plastic or glass surface is an artificial situation that significantly changes energy metabolism, shape and intracellular signaling, which in turn directly affects drug response. On the other hand, rodents as the most frequently used animal models have evolutionarily separated from primates about 100 million years ago, with significant differences in physiology, which frequently leads to results not reproducible in humans. As an alternative, spheroid technology and micro-organoids have evolved in the last decade to provide 3D context for cells similar to native tissue. However, organoids used for drug testing are usually just in the 50–100 micrometers range and thereby too small to mimic micro-environmental tissue conditions such as limited nutrient and oxygen availability. An attractive alternative offers 3D bioprinting as this allows fabrication of human tissue equivalents from scratch with hollow structures for perfusion and strict spatiotemporal control over the deposition of cells and extracellular matrix proteins. Thereby, tissue surrogates with defined geometry are fabricated that offer unique opportunities in exploring cellular cross-talk, mechanobiology and morphogenesis. These tissue-equivalents are also very attractive tools in drug testing, as bioprinting enables standardized production, parallelization, and application-tailored design of human tissue, of human disease models and patient-specific tissue avatars. This review, therefore, summarizes recent advances in 3D bioprinting technology and its application for drug screening.

scholarly journals From NAFLD to MAFLD: Aligning Translational In Vitro Research to Clinical Insights

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 161
Author(s):  
Alexandra Gatzios ◽  
Matthias Rombaut ◽  
Karolien Buyl ◽  
Joery De Kock ◽  
Robim M. Rodrigues ◽  
...  
Keyword(s):  
Liver Disease ◽  
Drug Development ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Drug Testing ◽  
Disease Modeling ◽  
In Vitro Models ◽  
Alcoholic Fatty Liver ◽  
Short Term Exposure

Although most same-stage non-alcoholic fatty liver disease (NAFLD) patients exhibit similar histologic sequelae, the underlying mechanisms appear to be highly heterogeneous. Therefore, it was recently proposed to redefine NAFLD to metabolic dysfunction-associated fatty liver disease (MAFLD) in which other known causes of liver disease such as alcohol consumption or viral hepatitis do not need to be excluded. Revised nomenclature envisions speeding up and facilitating anti-MAFLD drug development by means of patient stratification whereby each subgroup would benefit from distinct pharmacological interventions. As human-based in vitro research fulfils an irrefutable step in drug development, action should be taken as well in this stadium of the translational path. Indeed, most established in vitro NAFLD models rely on short-term exposure to fatty acids and use lipid accumulation as a phenotypic benchmark. This general approach to a seemingly ambiguous disease such as NAFLD therefore no longer seems applicable. Human-based in vitro models that accurately reflect distinct disease subgroups of MAFLD should thus be adopted in early preclinical disease modeling and drug testing. In this review article, we outline considerations for setting up translational in vitro experiments in the MAFLD era and allude to potential strategies to implement MAFLD heterogeneity into an in vitro setting so as to better align early drug development with future clinical trial designs.

Abstract 241: Retinoic Acid Promotes Metabolic Maturation of Human Embryonic Stem Cell-derived Cardiomyocytes

2020 ◽  
Vol 127 (Suppl_1) ◽  
Author(s):  
Shumei Miao ◽  
Xing Fang ◽  
Xiaoxiao Wang ◽  
Lingqun Ye ◽  
Jingsi Yang ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Retinoic Acid ◽  
Heart Development ◽  
Drug Testing ◽  
Disease Modeling ◽  
Time Window ◽  
Embryonic Stem ◽  
Early Time ◽  
Control Group ◽  
Cardiomyocyte Differentiation

Cardiomyocytes differentiated from human embryonic stem cells (hESCs) represent a promising cell source for heart repair, disease modeling and drug testing. However, improving the differentiation efficiency and maturation of hESC-derived cardiomyocytes (hESC-CMs) is still a major concern. Retinoic acid (RA) signaling plays multiple roles in heart development, and studies on RA can provide clues for understanding cardiomyocyte differentiation and maturation. In this study, we studied the roles of RA during cardiomyocyte differentiation and maturation, systematically. After adding RA at different stages of cardiomyocyte differentiation, we compared the efficiency of differentiation by quantitative real-time PCR and flow cytometry. We found that RA treatment at the lateral mesoderm stage (days 2-4) significantly improved cardiomyocyte differentiation, as evidenced by the upregulation of TNNT2, NKX2.5 and MYH6 on day 10 of differentiation. In addition, flow cytometry showed that the proportion of differentiated cardiomyocytes in the RA-treated group was significantly higher than that in control group. Furthermore, RA was added at different time intervals after purification to induce cardiomyocyte maturation. Our results demonstrated that RA treatment on days 15-20 increased cardiomyocyte area, sarcomere length, multinucleation and mitochondrial copy number, and promoted RNA splicing switch. Importantly, RA-treated cardiomyocytes showed decreased glycolysis and enhanced mitochondrial oxidative phosphorylation, with the increased utilization of fatty acid and exogenous pyruvate but not glutamine. In conclusion, our data indicated that RA treatment at an early time window (days 2-4) promotes the efficiency of cardiomyocyte differentiation and that RA treatment post beating (days 15-20) promotes cardiomyocyte metabolic maturation. The biphasic effects of RA provide new insights for improving cardiomyocyte differentiation and quality.

A 3D bioprinting system to produce human-scale tissue constructs with structural integrity

2016 ◽  
Vol 34 (3) ◽  
pp. 312-319 ◽  
Author(s):  
Hyun-Wook Kang ◽  
Sang Jin Lee ◽  
In Kap Ko ◽  
Carlos Kengla ◽  
James J Yoo ◽  
...  
Keyword(s):  
Structural Integrity ◽  
3D Bioprinting ◽  
Tissue Constructs ◽  
Human Scale

scholarly journals Pancreatic cancer-derived organoids – a disease modeling tool to predict drug response

2020 ◽  
Vol 8 (5) ◽  
pp. 594-606 ◽  
Author(s):  
Pierre-Olivier Frappart ◽  
Karolin Walter ◽  
Johann Gout ◽  
Alica K Beutel ◽  
Mareen Morawe ◽  
...  
Keyword(s):  
Drug Testing ◽  
Disease Modeling ◽  
Individualized Medicine ◽  
Expression Patterns ◽  
Culture Conditions ◽  
Ductal Adenocarcinoma ◽  
Small Scale ◽  
Comparative Genomic

Background Organotypic cultures derived from pancreatic ductal adenocarcinoma (PDAC) termed pancreatic ductal cancer organoids (PDOs) recapitulate the primary cancer and can be derived from primary or metastatic biopsies. Although isolation and culture of patient-derived pancreatic organoids were established several years ago, pros and cons for individualized medicine have not been comprehensively investigated to date. Methods We conducted a feasibility study, systematically comparing head-to-head patient-derived xenograft tumor (PDX) and PDX-derived organoids by rigorous immunohistochemical and molecular characterization. Subsequently, a drug testing platform was set up and validated in vivo. Patient-derived organoids were investigated as well. Results First, PDOs faithfully recapitulated the morphology and marker protein expression patterns of the PDXs. Second, quantitative proteomes from the PDX as well as from corresponding organoid cultures showed high concordance. Third, genomic alterations, as assessed by array-based comparative genomic hybridization, revealed similar results in both groups. Fourth, we established a small-scale pharmacotyping platform adjusted to operate in parallel considering potential obstacles such as culture conditions, timing, drug dosing, and interpretation of the results. In vitro predictions were successfully validated in an in vivo xenograft trial. Translational proof-of-concept is exemplified in a patient with PDAC receiving palliative chemotherapy. Conclusion Small-scale drug screening in organoids appears to be a feasible, robust and easy-to-handle disease modeling method to allow response predictions in parallel to daily clinical routine. Therefore, our fast and cost-efficient assay is a reasonable approach in a predictive clinical setting.

scholarly journals 3D bioprinting of functional tissue models for personalized drug screening and in vitro disease modeling

2018 ◽  
Vol 132 ◽  
pp. 235-251 ◽  
Author(s):  
Xuanyi Ma ◽  
Justin Liu ◽  
Wei Zhu ◽  
Min Tang ◽  
Natalie Lawrence ◽  
...  
Keyword(s):  
Drug Screening ◽  
Disease Modeling ◽  
3D Bioprinting ◽  
Functional Tissue ◽  
Tissue Models
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