Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening
Abstract
:1. Introduction
2. Methods
2.1. Chemicals and Plasticware
2.2. Human iPSC Culture
2.3. Neuronal Differentiation and Maintenance
2.4. 3D Neurosphere Culture
2.5. Cryosectioning and Immunocytochemistry (ICC) Staining
2.6. Apoptosis Assay
2.7. Transmission Electron Microscopy (TEM)
2.8. RT-qPCR Analysis
2.9. XBP1-Assay of Endoplasmic Reticulum Stress
2.10. Toxicity Treatments and ATP Viability Assay
2.11. Diametric and Total Protein Determination of the Spheroids
2.12. Neurite Outgrowth Assay
2.13. Statistical Analysis
3. Results
3.1. Three-Dimensional Spheroid Differentiation of iPSCs-Derived NSCs Revealed Complex Neuronal Cultures
3.2. Early 3D Neurospheres as a Neurotoxicity Model
3.3. Different Age of the 3D Neurospheres Represent Distinct Differentiation Stages in the Cytotoxicity Model
3.4. Compound-Specific Cellular Events Can be Detected in the 3D Neurospheres
3.5. Neurite Outgrowth Assay is Suitable to Determine the Effect of NT Compounds in the 3D Model
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Ethics approval and consent to participate
Consent for publication
Availability of Data and Material
Abbreviations
3D | three dimensional; |
AO | adverse outcome; |
BSA | bovine serum albumin; |
CAS | chemical abstracts service; |
CNS | central nervous system; |
Ctrl | control; |
D | day; |
DNT | developmental neurotoxicity; |
EC | effective concentration; |
ER | endoplasmic reticulum; |
FBS | fetal bovine serum; |
HE | Hematoxylin-Eosin; |
HTS | high-throughput screening; |
hiPSC | human induced pluripotent stem cell; |
ICC | immunocytochemistry; |
iPSC | induced pluripotent stem cell; |
NA | numeric aperture; |
NAM | new approach method; |
NEAA | non-essential amino acids; |
NIM | neural induction media; |
NMM | neural maintenance media; |
NPC | neural progenitor cell; |
NSC | neural stem cell; |
O/N | overnight; |
PBMC | peripheral blood mononuclear cells; |
PBS | phosphate buffer saline; |
PCR | polymerase chain reaction; |
PFA | Paraformaldehyde; |
POL/L | Poly-l-ornithine and Laminin; |
PSC | pluripotent stem cell; |
RT | room temperature; |
rTdT | recombinant terminal deoxynucleotidyl transferase; |
RT-PCR | reverse transcription polymerase chain reaction; |
TEM | transmission electron microscopy; |
TUNEL | terminal deoxynucleotidyl transferase dUTP nick end labeling. |
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Compound Name (CAS Number) | Known Effects of the Compound |
---|---|
Acrylamide 79-06-1 |
|
Colchicine 64-86-8 |
|
Doxorubicin 25316-40-9 |
|
Hexachlorophene 70-30-4 |
|
Ibuprofen 15687-27-1 |
|
Mercury(II) chloride 7487-94-7 |
|
Paracetamol 103-90-2 |
|
Paraquat 7 5365-73-0 |
|
Rifampicin 13292-46-1 |
|
Rotenone 83-79-4 |
|
Valproic acid 1069-66-5 |
|
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Kobolak, J.; Teglasi, A.; Bellak, T.; Janstova, Z.; Molnar, K.; Zana, M.; Bock, I.; Laszlo, L.; Dinnyes, A. Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening. Cells 2020, 9, 1122. https://doi.org/10.3390/cells9051122
Kobolak J, Teglasi A, Bellak T, Janstova Z, Molnar K, Zana M, Bock I, Laszlo L, Dinnyes A. Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening. Cells. 2020; 9(5):1122. https://doi.org/10.3390/cells9051122
Chicago/Turabian StyleKobolak, Julianna, Annamaria Teglasi, Tamas Bellak, Zofia Janstova, Kinga Molnar, Melinda Zana, Istvan Bock, Lajos Laszlo, and Andras Dinnyes. 2020. "Human Induced Pluripotent Stem Cell-Derived 3D-Neurospheres Are Suitable for Neurotoxicity Screening" Cells 9, no. 5: 1122. https://doi.org/10.3390/cells9051122