Covid-19 New

More Info

Open access Aims and Scope Instructions Editorial Guidelines Licensing Copyright

Author's satisfaction with

  • Friendly and hassle-free publication process
  • Less production time of articles
  • Constructive peer-review
  • Enhancing journal reputation
  • Regular feedback system
  • Quick response to authors' queries

Read More

Recently Viewed

Plant growth, Yield and Leaf Nutritional value of Jute (Corc Environmental Factors Affecting the Concentration of DNA in Why Down-managing Backlog Forensic DNA Case Entries Matters Scintigraphic non-invasive diagnosis of amyloid cardiomyopat Anomalies of coronary artery origin: About two cases

Read More

Most Viewed

Evaluation of Biostimulants Based on Recovered Protein Hydro Sinonasal Myxoma Extending into the Orbit in a 4-Year Old: A Feasibility study of magnetic sensing for detecting single-n Physical activity can change the physiological and psycholog Pediatric Dysgerminoma: Unveiling a Rare Ovarian Tumor

Read More

Open Journals

Clinical Images

For Authors Guide For Authors Benefits For Authors Article Processing Charge How To Write a Scientific Paper How To Write a Review Article Short Communication
For Reviewers Benefits For Reviewers How To Review Thanks To Reviewers
For Editors Benefits For Editors Thanks To Editors

Abstract

Review Article

Exploring Environmental Neurotoxicity Assessment Using Human Stem Cell-Derived Models

Narimane Kebieche*, Farzana Liakath Ali, Seungae Yim, Mohamed Ali, Claude Lambert and Rachid Soulimani

Published: 15 November, 2024 | Volume 8 - Issue 1 | Pages: 054-068

Neurotoxicity is increasingly recognized as a critical factor impacting long-term health, with growing evidence linking it to both neurodevelopmental and neurodegenerative diseases. Pesticides, widely used in agriculture and industry, have emerged as significant contributors to neurotoxic risk, given their capacity to disrupt key neurodevelopmental processes at low exposure levels. As conventional animal models present limitations in interspecies translation, human-derived neuron-based in vitro screening strategies are urgently needed to assess potential toxicants accurately. Human-induced pluripotent stem cells (hiPSCs) offer an innovative and scalable source for human-specific neuronal models that complement traditional animal-based approaches and support the development of predictive assays for neurotoxicity. Recent various stem cell models, including 2D cultures, 3D organoids, and microfluidic systems, are now available, advancing predictive neurotoxicology by simulating key aspects of human neural development and function. With the integration of High-Throughput (HT) and High-Content (HC) screening methodologies, these hiPSC-based systems enable efficient, large-scale evaluation of chemical effects on neural cells, enhancing our ability to detect early biomarkers of neurotoxic effects. Identifying early biomarkers of neurotoxic is essential to developing therapeutic interventions before irreversible damage occurs. This is particularly crucial in the context of developmental neurotoxicity, where early exposure to toxicants can have lifelong consequences. This review specifically presents an in-depth overview of the current progress in hiPSC-derived neural models and their applications in neurotoxicity testing, with a specific focus on their utility in assessing pesticide-induced neurotoxicity. Emphasizing future research priorities, we highlight the potential of these models to transform predictive toxicology, offering more human-relevant assessments and advancing the field toward a more precise evaluation of environmental neurotoxicants.

Read Full Article HTML DOI: 10.29328/journal.jsctt.1001044 Cite this Article Read Full Article PDF

Keywords:

Neurotoxicity; Neurodevelopmental diseases; Neurodegenerative diseases; Pesticides; Human-induced Pluripotent Stem Cells (hiPSCs); Developmental neurotoxicity; Predictive toxicology

References

  1. Grandjean P, Landrigan P. Developmental neurotoxicity of industrial chemicals. Lancet. 2006;368:2167–2178. Available from: https://doi.org/10.1016/s0140-6736(06)69665-7
  2. Grandjean P, Landrigan PJ. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014;13:330–338. Available from: https://doi.org/10.1016/s1474-4422(13)70278-3
  3. Heyer DB, Meredith RM. Environmental toxicology: Sensitive periods of development and neurodevelopmental disorders. NeuroToxicol. 2017;58:23–41. Available from: https://doi.org/10.1016/j.neuro.2016.10.017
  4. Landrigan PJ, Goldman LR. Children’s vulnerability to toxic chemicals: A challenge and opportunity to strengthen health and environmental policy. Health Aff (Millwood). 2011;30:842–850. Available from: https://doi.org/10.1377/hlthaff.2011.0151
  5. Kroon T, Sierksma MC, Meredith RM. Investigating mechanisms underlying neurodevelopmental phenotypes of autistic and intellectual disability disorders: A perspective. Front Syst Neurosci. 2013;7:75. Available from: https://doi.org/10.3389/fnsys.2013.00075
  6. Harris A, Seckl J. Glucocorticoids, prenatal stress and the programming of disease. Horm Behav. 2011;59:279–289. Available from: https://doi.org/10.1016/j.yhbeh.2010.06.007
  7. Raciti M, Ceccatelli S. Epigenetic mechanisms in developmental neurotoxicity. Neurotoxicol Teratol. 2018;66:94–101. Available from: https://doi.org/10.1016/j.ntt.2017.12.002
  8. Dagnino S. Unravelling the exposome: Conclusions and thoughts for the future. In: Dagnino S, Macherone A, editors. Unraveling the Exposome. Cham: Springer International Publishing. 2018; 425–437.
  9. Wild CP. Complementing the genome with an ‘exposome’: The outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev. 2005;14:1847–1850. Available from: https://doi.org/10.1158/1055-9965.epi-05-0456
  10. Feil R, Fraga MF. Epigenetics and the environment: Emerging patterns and implications. Nat Rev Genet. 2012;13:97–109. Available from: https://doi.org/10.1038/nrg3142
  11. Hartung T. On mapping the human toxome. ALTEX. 2011;28:83–93. Available from: https://doi.org/10.14573/altex.2011.2.083
  12. Hartung T. Toxicology for the twenty-first century. Nature. 2009;460:208–212. Available from: https://doi.org/10.1038/460208a
  13. Paparella M, Bennekou SH, Bal-Price A. An analysis of the limitations and uncertainties of in vivo developmental neurotoxicity testing and assessment to identify the potential for alternative approaches. Reprod Toxicol. 2020;96:327–336. Available from: https://doi.org/10.1016/j.reprotox.2020.08.002
  14. Hofrichter M, Nimtz L, Tigges J, Kabiri Y, Schröter F, Royer-Pokora B, et al. Comparative performance analysis of human iPSC-derived and primary neural progenitor cells (NPC) grown as neurospheres in vitro. Stem Cell Res. 2017;25:72–82. Available from: https://doi.org/10.1016/j.scr.2017.10.013
  15. Pamies D. Guidance document on Good Cell and Tissue Culture Practice 2.0 (GCCP 2.0). ALTEX. Epub ahead of print 2021. Available from: https://doi.org/10.14573/altex.2111011
  16. Liu W, Deng Y, Liu Y, Gong W, Deng W. Stem Cell Models for Drug Discovery and Toxicology Studies: Stem Cell Models For Drug Discovery And Toxicology. J Biochem Mol Toxicol. 2013;27:17–27. Available from: https://doi.org/10.1002/jbt.21470
  17. Biehl JK, Russell B. Introduction to Stem Cell Therapy. J Cardiovasc Nurs. 2009;24:98–103. Available from: https://doi.org/10.1097/jcn.0b013e318197a6a5
  18. Dulak J, Szade K, Szade A, Nowak W, Józkowicz A. Adult stem cells: hopes and hypes of regenerative medicine. Acta Biochim Pol. 2015;62:329–337. Available from: https://doi.org/10.18388/abp.2015_1023
  19. Seiler AEM, Spielmann H. The validated embryonic stem cell test to predict embryotoxicity in vitro. Nat Protoc. 2011;6:961–978. Available from: https://doi.org/10.1038/nprot.2011.348
  20. Jaramillo-Ferrada PA, Wolvetang EJ, Cooper-White JJ. Differential mesengenic potential and expression of stem cell-fate modulators in mesenchymal stromal cells from human-term placenta and bone marrow. J Cell Physiol. 2012;227:3234–3242. Available from: https://doi.org/10.1002/jcp.24014
  21. Visvader JE, Clevers H. Tissue-specific designs of stem cell hierarchies. Nat Cell Biol. 2016;18:349–355. Available from: https://doi.org/10.1038/ncb3332
  22. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676. Available from: https://doi.org/10.1016/j.cell.2006.07.024
  23. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, et al. Induced pluripotent stem cell lines derived from human somatic cells. Science. 2007;318:1917–1920. Available from: https://doi.org/10.1126/science.1151526
  24. Shtrichman R, Germanguz I, Eldor JI. Induced pluripotent stem cells (iPSCs) derived from different cell sources and their potential for regenerative and personalized medicine. CMM. 2013;13:792–805. Available from: https://doi.org/10.2174/1566524011313050010
  25. Perrier AL, Tabar V, Barberi T, Rubio ME, Bruses J, Topf N, et al. Derivation of midbrain dopamine neurons from human embryonic stem cells. Proc Natl Acad Sci USA. 2004;101:12543–12548. Available from: https://doi.org/10.1073/pnas.0404700101
  26. Stummann T, Bremer S. The possible impact of human embryonic stem cells on safety pharmacological and toxicological assessments in drug discovery and drug development. CSCR. 2008;3:117–130. Available from: https://doi.org/10.2174/157488808784223104
  27. Hartung T. Thoughts on limitations of animal models. Parkinsonism Relat Disord. 2008;14–S83. Available from: https://doi.org/10.1016/j.parkreldis.2008.04.003
  28. Zhao Z, Zhang D, Yang F, Xu M, Zhao S, Pan T, et al. Evolutionarily conservative and non-conservative regulatory networks during primate interneuron development revealed by single-cell RNA and ATAC sequencing. Cell Res. 2022;32:425–436. Available from: https://doi.org/10.1038/s41422-022-00635-9
  29. Kumar KK, Aboud AA, Bowman AB. The potential of induced pluripotent stem cells as a translational model for neurotoxicological risk. NeuroToxicol. 2012;33:518–529. Available from: https://doi.org/10.1016/j.neuro.2012.02.005
  30. Hu B-Y, Weick JP, Yu J, Ma LX, Zhang XQ, Thomson JA, et al. Neural differentiation of human induced pluripotent stem cells follows developmental principles but with variable potency. Proc Natl Acad Sci USA. 2010;107:4335–4340. Available from: https://doi.org/10.1073/pnas.0910012107
  31. Liu Q, Pedersen OZ, Peng J, Couture LA, Rao MS, Zeng X. Optimizing dopaminergic differentiation of pluripotent stem cells for the manufacture of dopaminergic neurons for transplantation. Cytotherapy. 2013;15:999–1010. Available from: https://doi.org/10.1016/j.jcyt.2013.03.006
  32. Wang S, Bates J, Li X, Schanz S, Chandler-Militello D, Levine C, et al. Human iPSC-derived oligodendrocyte progenitor cells can myelinate and rescue a mouse model of congenital hypomyelination. Cell Stem Cell. 2013;12:252–264. Available from: https://doi.org/10.1016/j.stem.2012.12.002
  33. Odawara A, Katoh H, Matsuda N, Suzuki I. Physiological maturation and drug responses of human induced pluripotent stem cell-derived cortical neuronal networks in long-term culture. Sci Rep. 2016;6:26181. Available from: https://doi.org/10.1038/srep26181
  34. Odawara A, Matsuda N, Ishibashi Y, Yokoi R, Suzuki I. Toxicological evaluation of convulsant and anticonvulsant drugs in human induced pluripotent stem cell-derived cortical neuronal networks using an MEA system. Sci Rep. 2018;8:10416. Available from: https://doi.org/10.1038/s41598-018-28835-7
  35. Tukker AM, de Groot MW, Wijnolts FM, Kasteel EE, Hondebrink L, Westerink RH. Is the time right for in vitro neurotoxicity testing using human iPSC-derived neurons? ALTEX. 2016;33(3):261–271. Available from: https://doi.org/10.14573/altex.1510091
  36. Little D, Ketteler R, Gissen P, Devine MJ. Using stem cell–derived neurons in drug screening for neurological diseases. Neurobiol Aging. 2019;78:130–141. Available from: https://doi.org/10.1016/j.neurobiolaging.2019.02.008
  37. Tukker AM, Wijnolts FMJ, de Groot A, Westerink RHS. Human iPSC-derived neuronal models for in vitro neurotoxicity assessment. NeuroToxicol. 2018;67:215–225. Available from: https://doi.org/10.1016/j.neuro.2018.06.007
  38. Tukker AM, Wijnolts FMJ, de Groot A, Westerink RHS. In vitro techniques for assessing neurotoxicity using human iPSC-derived neuronal models. In: Aschner M, Costa L, editors. Cell Culture Techniques. New York, NY: Springer New York; 2019; 17–35. Available from: https://dspace.library.uu.nl/handle/1874/392153
  39. Zhang P, Xia N, Reijo Pera RA. Directed dopaminergic neuron differentiation from human pluripotent stem cells. JoVE. 2014;51737. Available from: https://doi.org/10.3791/51737
  40. Liu Y, Liu H, Sauvey C, Yao L, Zarnowska ED, Zhang SC. Directed differentiation of forebrain GABA interneurons from human pluripotent stem cells. Nat Protoc. 2013;8:1670–1679. Available from: https://doi.org/10.1038/nprot.2013.106
  41. Sun AX, Yuan Q, Tan S, Xiao Y, Wang D, Khoo AT, et al. Direct induction and functional maturation of forebrain GABAergic neurons from human pluripotent stem cells. Cell Rep. 2016;16:1942–1953. Available from: https://doi.org/10.1016/j.celrep.2016.07.035
  42. Corti S, Nizzardo M, Simone C, Falcone M, Nardini M, Ronchi D, et al. Genetic correction of human induced pluripotent stem cells from patients with spinal muscular atrophy. Sci Transl Med. 2012;4. Available from: https://doi.org/10.1126/scitranslmed.3004108
  43. Sareen D, O’Rourke JG, Meera P, Muhammad AK, Grant S, Simpkinson M, et al. Targeting RNA foci in iPSC-derived motor neurons from ALS patients with a C9ORF72 repeat expansion. Sci Transl Med. 2013;5. Available from: https://doi.org/10.1126/scitranslmed.3007529
  44. Wen Z, Nguyen HN, Guo Z, Lalli MA, Wang X, Su Y, et al. Synaptic dysregulation in a human iPS cell model of mental disorders. Nature. 2014;515:414–418. Available from: https://doi.org/10.1038/nature13716
  45. Gunhanlar N, Shpak G, van der Kroeg M, Gouty-Colomer LA, Munshi ST, Lendemeijer B, et al. A simplified protocol for differentiation of electrophysiologically mature neuronal networks from human induced pluripotent stem cells. Mol Psychiatry. 2018;23:1336–1344. Available from: https://doi.org/10.1038/mp.2017.56
  46. Clevers H. Modeling development and disease with organoids. Cell. 2016;165:1586–1597. Available from: https://doi.org/10.1016/j.cell.2016.05.082
  47. Di Lullo E, Kriegstein AR. The use of brain organoids to investigate neural development and disease. Nat Rev Neurosci. 2017;18:573–584. Available from: https://doi.org/10.1038/nrn.2017.107
  48. Chandrasekaran A, Avci HX, Ochalek A, Rösingh LN, Molnár K, László L, et al. Comparison of 2D and 3D neural induction methods for the generation of neural progenitor cells from human induced pluripotent stem cells. Stem Cell Res. 2017;25:139–151. Available from: https://doi.org/10.1016/j.scr.2017.10.010
  49. Lancaster MA, Knoblich JA. Organogenesis in a dish: Modeling development and disease using organoid technologies. Science. 2014;345:1247125. Available from: https://doi.org/10.1126/science.1247125
  50. Elshazzly M, Lopez MJ, Reddy V, Caban O. Embryology, central nervous system. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. (accessed 17 June 2022). Available from: http://www.ncbi.nlm.nih.gov/books/NBK526024/
  51. Lancaster MA, Corsini NS, Wolfinger S, Gustafson EH, Phillips AW, Burkard TR, et al. Guided self-organization and cortical plate formation in human brain organoids. Nat Biotechnol. 2017;35:659–666. Available from: https://doi.org/10.1038/nbt.3906
  52. Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell. 2016;165:1238–1254. Available from: https://doi.org/10.1016/j.cell.2016.04.032
  53. Jo J, Xiao Y, Sun AX, Cukuroglu E, Tran HD, Göke J, et al. Midbrain-like organoids from human pluripotent stem cells contain functional dopaminergic and neuromelanin-producing neurons. Cell Stem Cell. 2016;19:248–257. Available from: https://doi.org/10.1016/j.stem.2016.07.005
  54. Fan P, Wang Y, Xu M, Han X, Liu Y. The application of brain organoids in assessing neural toxicity. Front Mol Neurosci. 2022;15:799397. Available from: https://doi.org/10.3389/fnmol.2022.799397
  55. Muguruma K, Nishiyama A, Kawakami H, Hashimoto K, Sasai Y. Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep. 2015;10:537–550. Available from: https://doi.org/10.1016/j.celrep.2014.12.051
  56. Birey F, Andersen J, Makinson CD, Islam S, Wei W, Huber N, et al. Assembly of functionally integrated human forebrain spheroids. Nature. 2017;545:54–59. Available from: https://doi.org/10.1038/nature22330
  57. Mansour AA, Gonçalves JT, Bloyd CW, Li H, Fernandes S, Quang D, et al. An in vivo model of functional and vascularized human brain organoids. Nat Biotechnol. 2018;36:432–441. Available from: https://doi.org/10.1038/nbt.4127
  58. Shi Y, Sun L, Wang M, Liu J, Zhong S, Li R, et al. Vascularized human cortical organoids (vOrganoids) model cortical development in vivo. PLoS Biol. 2020;18. Available from: https://doi.org/10.1371/journal.pbio.3000705
  59. Schultz L, Zurich M-G, Culot M, da Costa A, Landry C, Bellwon P, et al. Evaluation of drug-induced neurotoxicity based on metabolomics, proteomics and electrical activity measurements in complementary CNS in vitro models. Toxicol In Vitro. 2015;30:138–165. Available from: https://doi.org/10.1016/j.tiv.2015.05.016
  60. Lippmann ES, Azarin SM, Kay JE, Nessler RA, Wilson HK, Al-Ahmad A, et al. Derivation of blood-brain barrier endothelial cells from human pluripotent stem cells. Nat Biotechnol. 2012;30:783–791. Available from: https://doi.org/10.1038/nbt.2247
  61. Wilson HK, Canfield SG, Hjortness MK, Palecek SP, Shusta EV. Exploring the effects of cell seeding density on the differentiation of human pluripotent stem cells to brain microvascular endothelial cells. Fluids Barriers CNS. 2015;12:13. Available from: https://doi.org/10.1186/s12987-015-0007-9
  62. Lippmann ES, Al-Ahmad A, Azarin SM, Palecek SP, Shusta EV. A retinoic acid-enhanced, multicellular human blood-brain barrier model derived from stem cell sources. Sci Rep. 2015;4:4160. Available from: https://doi.org/10.1038/srep04160
  63. Wang YI, Abaci HE, Shuler ML. Microfluidic blood–brain barrier model provides in vivo‐like barrier properties for drug permeability screening. Biotechnol Bioeng. 2017;114:184–194. Available from: https://doi.org/10.1002/bit.26045
  64. Vatine GD, Barrile R, Workman MJ, Sances S, Barriga BK, Rahnama M, et al. Human iPSC-derived blood-brain barrier chips enable disease modeling and personalized medicine applications. Cell Stem Cell. 2019;24(6):995-1005.e6. Available from: https://doi.org/10.1016/j.stem.2019.05.011
  65. Pham MT, Pollock KM, Rose MD, Cary WA, Stewart HR, Zhou P, et al. Generation of human vascularized brain organoids. NeuroReport. 2018;29:588–593. Available from: https://doi.org/10.1097/wnr.0000000000001014
  66. Cakir B, Xiang Y, Tanaka Y, Kural MH, Parent M, Kang YJ, et al. Engineering of human brain organoids with a functional vascular-like system. Nat Methods. 2019;16:1169–1175. Available from: https://doi.org/10.1038/s41592-019-0586-5
  67. Perestrelo A, Águas A, Rainer A, Forte G. Microfluidic Organ/Body-on-a-Chip devices at the convergence of biology and microengineering. Sensors. 2015;15:31142–31170. Available from: https://doi.org/10.3390/s151229848
  68. Zhuang Q-C, Ning R-Z, Ma Y, Lin J-M. Recent developments in microfluidic chip for in vitro cell-based research. Chin J Anal Chem. 2016;44:522–532. Available from: https://doi.org/10.1016/S1872-2040(16)60919-2
  69. Sances S, Ho R, Vatine G, West D, Laperle A, Meyer A, et al. Human iPSC-derived endothelial cells and microengineered organ-chip enhance neuronal development. Stem Cell Reports. 2018;10:1222–1236. Available from: https://doi.org/10.1016/j.stemcr.2018.02.012
  70. Liu L, Koo Y, Russell T, Yun Y. A three-dimensional brain-on-a-chip using human iPSC-derived GABAergic neurons and astrocytes. Methods Mol Biol. 2022;2492:117-128. Available from: https://doi.org/10.1007/978-1-0716-2289-6_6
  71. Faley SL, Neal EH, Wang JX, Bosworth AM, Weber CM, Balotin KM, et al. iPSC-derived brain endothelium exhibits stable, long-term barrier function in perfused hydrogel scaffolds. Stem Cell Reports. 2019;12:474–487. Available from: https://doi.org/10.1016/j.stemcr.2019.01.009
  72. Spijkers XM, Pasteuning-Vuhman S, Dorleijn JC, Vulto P, Wevers NR, Pasterkamp RJ. A directional 3D neurite outgrowth model for studying motor axon biology and disease. Sci Rep. 2021;11:2080. Available from: https://doi.org/10.1038/s41598-021-81335-z
  73. Pei Y, Peng J, Behl M, Sipes NS, Shockley KR, Rao MS, et al. Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes. Brain Res. 2016;1638:57–73. Available from: https://doi.org/10.1016/j.brainres.2015.07.048
  74. Bose R, Spulber S, Ceccatelli S. The threat posed by environmental contaminants on neurodevelopment: What can we learn from neural stem cells? Int J Mol Sci. 2023;24:4338. Available from: https://doi.org/10.3390/ijms24054338
  75. Bal-Price AK, Coecke S, Costa L, Crofton KM, Fritsche E, Goldberg A, et al. Advancing the science of developmental neurotoxicity (DNT): Testing for better safety evaluation. ALTEX. 2012;29(2):202-215. Available from: https://doi.org/10.14573/altex.2012.2.202
  76. Bal-Price AK, Hogberg HT, Buzanska L, Lenas P, van Vliet E, Hartung T. In vitro developmental neurotoxicity (DNT) testing: Relevant models and endpoints. NeuroToxicology. 2010;31:545–554. Available from: https://doi.org/10.1016/j.neuro.2009.11.006
  77. Fritsche E, Grandjean P, Crofton KM, Aschner M, Goldberg A, Heinonen T, et al. Consensus statement on the need for innovation, transition and implementation of developmental neurotoxicity (DNT) testing for regulatory purposes. Toxicol Appl Pharmacol. 2018;354:3–6. Available from: https://doi.org/10.1016/j.taap.2018.02.004
  78. Fritsche E, Barenys M, Klose J, Masjosthusmann S, Nimtz L, Schmuck M, et al. Corrigendum to “Current availability of stem cell-based in vitro methods for developmental neurotoxicity (DNT) testing.” Toxicol Sci. 2018;165:531–531. Available from: https://doi.org/10.1093/toxsci/kfy195
  79. Fritsche E, Barenys M, Klose J, Masjosthusmann S, Nimtz L, Schmuck M, et al. Development of the concept for stem cell-based developmental neurotoxicity evaluation. Toxicol Sci. 2018;165:14–20. Available from: https://doi.org/10.1093/toxsci/kfy175
  80. Paparella M, Bennekou SH, Bal-Price A. An analysis of the limitations and uncertainties of in vivo developmental neurotoxicity testing and assessment to identify the potential for alternative approaches. Reprod Toxicol. 2020;96:327-336. Available from: https://doi.org/10.1016/j.reprotox.2020.08.002
  81. Bal-Price A, Hogberg HT, Crofton KM, Daneshian M, FitzGerald RE, Fritsche E. Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity. ALTEX 2018;306–352. Available from: https://doi.org/10.14573/altex.1712081
  82. Bal-Price A, Pistollato F, Sachana M, Bopp SK, Munn S, Worth A. Strategies to improve the regulatory assessment of developmental neurotoxicity (DNT) using in vitro methods. Toxicol Appl Pharmacol. 2018;354:7–18. Available from: https://doi.org/10.1016/j.taap.2018.02.008
  83. Hrstka SCL, Ankam S, Agac B, Klein JP, Moore RA, Narapureddy B, et al. Proteomic analysis of human iPSC-derived sensory neurons implicates cell stress and microtubule dynamics dysfunction in bortezomib-induced peripheral neurotoxicity. Experimental Neurology 2021;335:113520. Available from: https://doi.org/10.1016/j.expneurol.2020.113520
  84. Bal-Price A, Hogberg HT, Crofton KM, Daneshian M, FitzGerald RE, Fritsche E, et al. Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity. ALTEX 2018;35:306–352. Available from: https://doi.org/10.14573/altex.1712081
  85. Chen L, Yoo S-E, Na R, Liu Y, Ran Q. Cognitive impairment and increased Aβ levels induced by paraquat exposure are attenuated by enhanced removal of mitochondrial H2O2. Neurobiology of Aging 2012;33:432.e15-432.e26. Available from: https://doi.org/10.1016/j.neurobiolaging.2011.01.008
  86. De Felice A, Scattoni ML, Ricceri L, Calamandrei G. Prenatal exposure to a common organophosphate insecticide delays motor development in a mouse model of idiopathic autism. PLoS One. 2015;10(3). Available from: https://doi.org/10.1371/journal.pone.0121663
  87. Kardas F, Bayram AK, Demirci E, Akin L, Ozmen S, Kendirci M, et al. Increased serum phthalates (MEHP, DEHP) and bisphenol A concentrations in children with autism spectrum disorder: The role of endocrine disruptors in autism etiopathogenesis. J Child Neurol. 2016;31(7):629–635. Available from: https://doi.org/10.1177/0883073815609150
  88. Li G, Kim C, Kim J, Yoon H, Zhou H, Kim J. Common pesticide, dichlorodiphenyltrichloroethane (DDT), increases amyloid-β levels by impairing the function of ABCA1 and IDE: Implication for Alzheimer’s disease. J Alzheimers Dis. 2015;46(1):109–122. Available from: https://doi.org/10.3233/jad-150024
  89. Pearson BL, Simon JM, McCoy ES, Salazar G, Fragola G, Zylka MJ. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration. Nat Commun. 2016;7:11173. Available from: https://doi.org/10.1038/ncomms11173
  90. Richardson JR, Taylor MM, Shalat SL, Guillot TS, Caudle WM, Hossain MM, et al. Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder. FASEB J. 2015;29(5):1960–1972. Available from: https://doi.org/10.1096/fj.14-260901
  91. Shelton JF, Geraghty EM, Tancredi DJ, Delwiche LD, Schmidt RJ, Ritz B, et al. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The CHARGE study. Environ Health Perspect. 2014;122(10):1103–1109. Available from: https://doi.org/10.1289/ehp.1307044
  92. Tyler CR, Allan AM. The effects of arsenic exposure on neurological and cognitive dysfunction in human and rodent studies: A review. Curr Envir Health Rpt. 2014;1(2):132–147. Available from: https://doi.org/10.1007/s40572-014-0012-1
  93. von Ehrenstein OS, Ling C, Cui X, Cockburn M, Park AS, Yu F, Wu J, et al. Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: Population-based case-control study. BMJ. 2019;365. Available from: https://doi.org/10.1136/bmj.l962
  94. Wang B, Du Y. Cadmium and its neurotoxic effects. Oxid Med Cell Longev. 2013;2013:1–12. Available from: https://doi.org/10.1155/2013/898040
  95. Li S, Zhang L, Huang R, Xu T, Parham F, Behl M, et al. Evaluation of chemical compounds that inhibit neurite outgrowth using GFP-labeled iPSC-derived human neurons. NeuroToxicol. 2021;83:137–145. Available from: https://doi.org/10.1016/j.neuro.2021.01.003
  96. Di Consiglio E, Pistollato F, Mendoza-De Gyves E, Bal-Price A, Testai E. Integrating biokinetics and in vitro studies to evaluate developmental neurotoxicity induced by chlorpyrifos in human iPSC-derived neural stem cells undergoing differentiation towards neuronal and glial cells. Reprod Toxicol. 2020;98:174–188. Available from: https://doi.org/10.1016/j.reprotox.2020.09.010
  97. Radio NM, Breier JM, Shafer TJ, Mundy WR. Assessment of chemical effects on neurite outgrowth in PC12 cells using high content screening. Toxicol Sci. 2008;105(1):106–118. Available from: https://doi.org/10.1093/toxsci/kfn114
  98. Kamata S, Hashiyama R, Hana-ika H, Ohkubo I, Saito R, et al. Cytotoxicity comparison of 35 developmental neurotoxicants in human induced pluripotent stem cells (iPSC), iPSC-derived neural progenitor cells, and transformed cell lines. Toxicol in Vitro. 2020;69:104999. Available from: https://doi.org/10.1016/j.tiv.2020.104999
  99. Pistollato F, de Gyves EM, Carpi D, Bopp SK, Nunes C, Worth A, et al. Assessment of developmental neurotoxicity induced by chemical mixtures using an adverse outcome pathway concept. Environ Health. 2020;19:23. Available from: https://doi.org/10.1186/s12940-020-00578-x
  100. Davidsen N, Lauvås AJ, Myhre O, Ropstad E, Carpi D, Gyves EM, et al. Exposure to human relevant mixtures of halogenated persistent organic pollutants (POPs) alters neurodevelopmental processes in human neural stem cells undergoing differentiation. Reprod Toxicol. 2021;100:17–34. Available from: https://doi.org/10.1016/j.reprotox.2020.12.013
  101. Park SM, Jo NR, Lee B, Jung EM, Lee SD, Jeung EB, et al. Establishment of a developmental neurotoxicity test by Sox1-GFP mouse embryonic stem cells. Reprod Toxicol. 2021;104:96–105. Available from: https://doi.org/10.1016/j.reprotox.2021.07.004
  102. Ishibashi Y, Nagafuku N, Kanda Y, Suzuki I. Evaluation of neurotoxicity for pesticide-related compounds in human iPS cell-derived neurons using microelectrode array. Toxicol in Vitro. 2023;93:105668. Available from: https://doi.org/10.1016/j.tiv.2023.105668
  103. Bartmann K, Bendt F, Dönmez A, Haag D, Keßel HE, Masjosthusmann S, et al. A human iPSC-based in vitro neural network formation assay to investigate neurodevelopmental toxicity of pesticides. ALTEX. 2023;40(3):452–470. Available from: https://doi.org/10.14573/altex.2206031
  104. Paul KC, Krolewski RC, Lucumi Moreno E, Blank J, Holton KM, Ahfeldt T, et al. A pesticide and iPSC dopaminergic neuron screen identifies and classifies Parkinson-relevant pesticides. Nat Commun. 2023;14(1):2803. Available from: https://doi.org/10.1038/s41467-023-38215-z
  105. Garcia SJ, Seidler FJ, Slotkin TA. Developmental neurotoxicity elicited by prenatal or postnatal chlorpyrifos exposure: Effects on neurospecific proteins indicate changing vulnerabilities. Environ Health Perspect. 2003;111(3):297–303. Available from: https://doi.org/10.1289/ehp.5791
  106. Tsuji R, Crofton KM. Developmental neurotoxicity guideline study: Issues with methodology, evaluation and regulation. Congenit Anomal. 2012;52(3):122–128. Available from: https://doi.org/10.1111/j.1741-4520.2012.00374.x
  107. Bal-Price A, Hogberg HT, Crofton KM, Daneshian M, FitzGerald RE, Fritsche E, et al. Recommendation on test readiness criteria for new approach methods in toxicology: Exemplified for developmental neurotoxicity. ALTEX. 2018;35(3):306–352. Available from: https://doi.org/10.14573/altex.1712081
  108. Pamies D, Block K, Lau P, Gribaldo L, Pardo CA, Barreras P, et al. Rotenone exerts developmental neurotoxicity in a human brain spheroid model. Toxicol Appl Pharmacol. 2018;354:101–114. Available from: https://doi.org/10.1016/j.taap.2018.02.003
  109. Modafferi S, Zhong X, Kleensang A, Murata Y, Fagiani F, Pamies D, et al. Gene–environment interactions in developmental neurotoxicity: A case study of synergy between chlorpyrifos and CHD8 knockout in human brainspheres. Environ Health Perspect. 2021;129(7):077001. Available from: https://doi.org/10.1289/ehp8580
  110. Lam D, Enright HA, Cadena J, George VK, Soscia DA, Tooker AC, et al. Spatiotemporal analysis of 3D human iPSC-derived neural networks using a 3D multi-electrode array. Front Cell Neurosci. 2023;17:1287089. Available from: https://doi.org/10.3389/fncel.2023.1287089
  111. Mariani A, Comolli D, Fanelli R, Forloni G, De Paola M. Neonicotinoid pesticides affect developing neurons in experimental mouse models and in human induced pluripotent stem cell (iPSC)-derived neural cultures and organoids. Cells. 2024;13(5):1295. Available from: https://doi.org/10.3390/cells13151295
  112. Kobolak J, Teglasi A, Bellak T, Janstova Z, Molnar K, Zana M, et al. Human induced pluripotent stem cell-derived 3D-neurospheres are suitable for neurotoxicity screening. Cells. 2020;9(5):1122. Available from: https://doi.org/10.3390/cells9051122
  113. Sirenko O, Parham F, Dea S, Sodhi N, Biesmans S, Mora-Castilla S, et al. Functional and mechanistic neurotoxicity profiling using human iPSC-derived neural 3D cultures. Toxicol Sci. 2019;167(1):58–76. Available from: https://doi.org/10.1093/toxsci/kfy218
  114. Campisi M, Shin Y, Osaki T, Hajal C, Chiono V, Kamm RD. 3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes and astrocytes. Biomaterials. 2018;180:117–129. Available from: https://doi.org/10.1016/j.biomaterials.2018.07.014
  115. Picollet-D’hahan N, Zuchowska A, Lemeunier I, Le Gac S. Multiorgan-on-a-chip: A systemic approach to model and decipher inter-organ communication. Trends Biotechnol. 2021;39(7):788–810. Available from: https://doi.org/10.1016/j.tibtech.2020.11.014
  116. Koo Y, Hawkins BT, Yun Y. Three-dimensional (3D) tetra-culture brain on chip platform for organophosphate toxicity screening. Sci Rep. 2018;8:2841. Available from: https://doi.org/10.1038/s41598-018-20876-2
  117. Liu L, Koo Y, Akwitti C, Russell T, Gay E, Laskowitz DT, et al. Three-dimensional (3D) brain microphysiological system for organophosphates and neurochemical agent toxicity screening. PLoS One. 2019;14(11). Available from: https://doi.org/10.1371/journal.pone.0224657
  118. Amend N, Koller M, Schmitt C, Worek F, Wille T. The suitability of a polydimethylsiloxane-based (PDMS) microfluidic two compartment system for the toxicokinetic analysis of organophosphorus compounds. Toxicol Lett. 2023;388:24–29. Available from: https://doi.org/10.1016/j.toxlet.2023.10.007
  119. Smirnova L, Hogberg HT, Leist M, Hartung T. Developmental neurotoxicity – Challenges in the 21st century and in vitro opportunities. ALTEX. 2014;31(2):129–156. Available from: https://doi.org/10.14573/altex.1403271
  120. Augustyniak J, Lenart J, Zychowicz M, Lipka G, Gaj P, Kolanowska M, et al. Sensitivity of hiPSC-derived neural stem cells (NSC) to pyrroloquinoline quinone depends on their developmental stage. Toxicol In Vitro. 2017;45:434–444. Available from: https://doi.org/10.1016/j.tiv.2017.05.017
  121. Pei Y, Sierra G, Sivapatham R, Swistowski A, Rao MS, Zeng X. A platform for rapid generation of single and multiplexed reporters in human iPSC lines. Sci Rep. 2015;5:9205. Available from: https://doi.org/10.1038/srep09205
  122. Pei Y, Peng J, Behl M, Sipes NS, Shockley KR, Rao MS, et al. Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons, and astrocytes. Brain Res. 2016;1638:57–73. Available from: https://doi.org/10.1016/j.brainres.2015.07.048
  123. Pistollato F, Carpi D, Mendoza-de Gyves E, Paini A, Bopp SK, Worth A, et al. Combining in vitro assays and mathematical modelling to study developmental neurotoxicity induced by chemical mixtures. Reprod Toxicol. 2021;105:101–119. Available from: https://doi.org/10.1016/j.reprotox.2021.08.007
  124. Rana P, Luerman G, Hess D, Rubitski E, Adkins K, Somps C. Utilization of iPSC-derived human neurons for high-throughput drug-induced peripheral neuropathy screening. Toxicol In Vitro. 2017;45:111–118. Available from: https://doi.org/10.1016/j.tiv.2017.08.014
  125. Shirakawa T, Suzuki I. Approach to neurotoxicity using human iPSC neurons: Consortium for safety assessment using human iPS cells. Curr Pharm Biotechnol. 2020;21(11):780–786. Available from: https://doi.org/10.2174/1389201020666191129103730
  126. Sirenko O, Parham F, Dea S, Sodhi N, Biesmans S, Mora-Castilla S, et al. Functional and mechanistic neurotoxicity profiling using human iPSC-derived neural 3D cultures. Toxicol Sci. 2019;167(1):58–76. Available from: https://doi.org/10.1093/toxsci/kfy218
  127. Tukker AM, Wijnolts FMJ, de Groot A, Westerink RHS. Applicability of hiPSC-derived neuronal cocultures and rodent primary cortical cultures for in vitro seizure liability assessment. Toxicol Sci. 2020;178(1):71–87. Available from: https://doi.org/10.1093/toxsci/kfaa136
  128. Wellens S, Dehouck L, Chandrasekaran V, Singh P, Loiola RA, Sevin E, et al. Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021;73:105112. Available from: https://doi.org/10.1016/j.tiv.2021.105112
  129. Slavin I, Dea S, Arunkumar P, Sodhi N, Montefusco S, Siqueira-Neto J, et al. Human iPSC-derived 2D and 3D platforms for rapidly assessing developmental, functional, and terminal toxicities in neural cells. Int J Mol Sci. 2021;22(4):1908. Available from: https://doi.org/10.3390/ijms22041908
  130. Pamies D, Wiersma D, Katt ME, Zhao L, Burtscher J, Harris G, et al. Human iPSC 3D brain model as a tool to study chemical-induced dopaminergic neuronal toxicity. Neurobiol Dis. 2022;169:105719. Available from: https://doi.org/10.1016/j.nbd.2022.105719
  131. Pomeshchik Y, Klementieva O, Gil J, Martinsson I, Hansen MG, de Vries T, et al. Human iPSC-derived hippocampal spheroids: An innovative tool for stratifying Alzheimer disease patient-specific cellular phenotypes and developing therapies. Stem Cell Rep. 2020;15(2):256–273. Available from: https://doi.org/10.1016/j.stemcr.2020.06.001
  132. Liu L, Koo Y, Russell T, Gay E, Li Y, Yun Y. Three-dimensional brain-on-chip model using human iPSC-derived GABAergic neurons and astrocytes: Butyrylcholinesterase post-treatment for acute malathion exposure. PLoS One. 2020;15(4). Available from: https://doi.org/10.1371/journal.pone.0230335
  133. Campisi M, Shin Y, Osaki T, Hajal C, Chiono V, Kamm RD. 3D self-organized microvascular model of the human blood-brain barrier with endothelial cells, pericytes, and astrocytes. Biomaterials. 2018;180:117–129. Available from: https://doi.org/10.1016/j.biomaterials.2018.07.014
  134. Lee C-T, Bendriem RM, Wu WW, Shen RF. 3D brain organoids derived from pluripotent stem cells: promising experimental models for brain development and neurodegenerative disorders. J Biomed Sci. 2017;24:59. Available from: https://doi.org/10.1186/s12929-017-0362-8
  135. Potjewyd G, Kellett KAB, Hooper NM. 3D hydrogel models of the neurovascular unit to investigate blood–brain barrier dysfunction. Neuronal Signaling. 2021;5(4). Available from: https://doi.org/10.1042/ns20210027
  136. Xiao S, Coppeta JR, Rogers HB, Isenberg BC, Zhu J, Olalekan SA, et al. A microfluidic culture model of the human reproductive tract and 28-day menstrual cycle. Nat Commun. 2017;8:14584. Available from: https://doi.org/10.1038/ncomms14584
  137. Taylor AM, Blurton-Jones M, Rhee SW, Cribbs DH, Cotman CW, Jeon NL. A microfluidic culture platform for CNS axonal injury, regeneration and transport. Nat Methods. 2005;2(9):599–605. Available from: https://doi.org/10.1038/nmeth777
  138. Bang S, Lee S, Choi N, Kim HN. Emerging brain‐pathophysiology‐mimetic platforms for studying neurodegenerative diseases: Brain organoids and brains‐on‐a‐ Adv Healthcare Mater. 2021;10(8):2002119. Available from: https://doi.org/10.1002/adhm.202002119
  139. Koo Y, Hawkins BT, Yun Y. Three-dimensional (3D) tetra-culture brain on chip platform for organophosphate toxicity screening. Sci Rep. 2018;8:2841. Available from: https://doi.org/10.1038/s41598-018-20876-2
  140. Lanciotti A, Brignone MS, Macioce P, Visentin S. Human iPSC-derived astrocytes: A powerful tool to study primary astrocyte dysfunction in the pathogenesis of rare leukodystrophies. Int J Mol Sci. 2021;23(1):274. Available from: https://doi.org/10.3390/ijms23010274
  141. Koo Y, Hawkins BT, Yun Y. Three-dimensional (3D) tetra-culture brain on chip platform for organophosphate toxicity screening. Sci Rep. 2018;8:2841. Available from: https://doi.org/10.1038/s41598-018-20876-2
  142. Linville RM, DeStefano JG, Sklar MB, Xu Z, Farrell AM, Bogorad MI, et al. Human iPSC-derived blood-brain barrier microvessels: validation of barrier function and endothelial cell behavior. Biomaterials. 2019;190–191:24–37. Available from: https://doi.org/10.1016/j.biomaterials.2018.10.023
  143. Middelkamp HHT, Verboven AHA, De Sá Vivas AG, Schoenmaker C, Klein Gunnewiek TM, Passier R, et al. Cell type-specific changes in transcriptomic profiles of endothelial cells, iPSC-derived neurons and astrocytes cultured on microfluidic chips. Sci Rep. 2021;11:2281. Available from: https://doi.org/10.1038/s41598-021-81933-x
  144. Popova G, Soliman SS, Kim CN, Keefe MG, Hennick KM, Jain S, et al. Human microglia states are conserved across experimental models and regulate neural stem cell responses in chimeric organoids. Cell Stem Cell. 2021;28(12):2153-2166.e6. Available from: https://doi.org/10.1016/j.stem.2021.08.015
  145. Soubannier V, Maussion G, Chaineau M, Sigutova V, Rouleau G, Durcan TM, et al. Characterization of human iPSC-derived astrocytes with potential for disease modeling and drug discovery. Neurosci Lett. 2020;731:135028. Available from: https://doi.org/10.1016/j.neulet.2020.135028
  146. Wörsdörfer P, Dalda N, Kern A, Krüger S, Wagner N, Kwok CK, et al. Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells. Sci Rep. 2019;9:15663. Available from: https://doi.org/10.1038/s41598-019-52204-7
  147. Zhang Y, Sloan SA, Clarke LE, Caneda C, Plaza CA, Blumenthal PD, et al. Purification and characterization of progenitor and mature human astrocytes reveals transcriptional and functional differences with mouse. Neuron. 2016;89:37–53. Available from: https://doi.org/10.1016/j.neuron.2015.11.013
  148. Nix C, Ghassemi M, Crommen J, Fillet M. Overview on microfluidics devices for monitoring brain disorder biomarkers. TrAC Trends in Analytical Chemistry. 2022;155:116693. Available from: https://scite.ai/reports/overview-on-microfluidics-devices-for-A3rxYKme
  149. Chang C-Y, Ting H-C, Liu C-A, Su HL, Chiou TW, Harn HJ, et al. Induced pluripotent stem cells: A powerful neurodegenerative disease modeling tool for mechanism study and drug discovery. Cell Transplant. 2018;27:1588–1602. Available from: https://doi.org/10.1177/0963689718775406
  150. Li S, Xia M. Review of high-content screening applications in toxicology. Arch Toxicol. 2019;93:3387–3396. Available from: https://doi.org/10.1007/s00204-019-02593-5
  151. Zhang Q, Caudle WM, Pi J, Bhattacharya S, Andersen ME, Kaminski NE, et al. Embracing systems toxicology at single-cell resolution. Curr Opin Toxicol. 2019;16:49–57. Available from: https://doi.org/10.1016/j.cotox.2019.04.003
  152. Ashammakhi N, Darabi MA, Çelebi‐Saltik B, Tutar R, Hartel MC, Lee J, et al. Microphysiological systems: Next generation systems for assessing toxicity and therapeutic effects of nanomaterials. Small Methods. 2020;4:1900589. Available from: https://doi.org/10.1002/smtd.201900589
  153. Mayr A, Klambauer G, Unterthiner T, Hochreiter S. DeepTox: Toxicity prediction using deep learning. Front Environ Sci. 2016;3. Available from: http://dx.doi.org/10.3389/fenvs.2015.00080
  154. Srivastava A, Hanig JP. Quantitative neurotoxicology: Potential role of artificial intelligence/deep learning approach. J Appl Toxicol. 2021;41:996–1006. Available from: https://doi.org/10.1002/jat.4098
  155. Myllynen P, Pasanen M, Pelkonen O. Human placenta: A human organ for developmental toxicology research and biomonitoring. Placenta. 2005;26:361–371. Available from: https://doi.org/10.1016/j.placenta.2004.09.006
  156. Rice D, Barone S. Critical periods of vulnerability for the developing nervous system: Evidence from humans and animal models. Environ Health Perspect. 2000;108:511–533. Available from: https://doi.org/10.1289/ehp.00108s3511

Figures:

Figure 1

Figure 1

Similar Articles

Recently Viewed

Read More

Most Viewed

Read More

Contact

Editorial Office Emails:

info@hspioa.org

amelia.sandra@hspioa.us

elena.maya@hspioa.us

Select by Volume & Issue

Submit Manuscript Information for Authors Advisory Board Rss Feed Articles Rss Feed

Most Viewed Keywords

University/Institution

Select and search by University/Institution.

Articles by Country

Select and search by country to get related articles.

Testmonials

I would like to thank JPRA for taking this decision. I understand the effort it represents for you. I'm truly happy to have the paper published in JPRA. And I'll certainly consider JPRA for my next publications as I was satisfied of the service provided, the efficiency and promptness of the interactions we had.

Emmanuel BUSATO

Publishing with the International Journal of Clinical and Experimental Ophthalmology was a rewarding experience as review process was thorough and brisk. Their visibility online is second to none as their published articles appear in all search engines. I will encourage researchers to publish with them.

Elizabeth Awoyesuku

“The choice to submit the forensic case study to the Journal of Addiction Therapy and Research was dictated by the match between the content and the potential readership. The publication process proved to be expedient and we were provided with constructive feedback from reviewers. The final article layout is attractive and conforms to standards. All-in-all, it has been a rewarding process.”

Elisabeth H Wiig

Archives of Vascular Medicine is one of the top class journal for vascular medicine with highly interesting topics. You did a professional and great Job!

Elias Noory

Thank you very much. I think the review process and all of what concerns the administration of the publication concerning our paper has been excellent. The nice and quick answers have been very good I think.

Doris Nilsson

Journal of Pulmonary and Respiratory Research is good journal for respiratory research purposes. It takes 2-3 weeks maximum for review of the manuscript to get published and any corrections to be made in the manuscript. It needs good articles and studies to get publish in the respiratory medicine. I am really glad that this journal editors helped me to get my case report published.

Divya Khanduja

Thanks you and your colleague for the great help for our publication. You always provide prompt responses and high quality of service. I am so happy to have you working with me. Thanks again!

Diana (Ding) Dai

Service and process were excellent as was the “look” of the article when published.

Deane Waldman

Great, thank you! It was very efficient working w/ your group. Very thorough reviews (i.e., plagiarism, peer, etc.). Would certainly recommend that future authors consider working w/ your group.

David W Brett

Your services are very good

Chukwuka Ireju Onyinye

I very much appreciate the humanitarian services provided in my stead by this journal/publisher. It exhibits total absence of editorial impertinence. As an Author, I have been guided to have a fruitful experience. The editorial care is highly commendable.

Chrysanthus Chukwuma

"An amazing experience with the Journal of Advanced Pediatrics and Child Health. Very fast blind review with pertinent corrections and suggestions. I highly recommand both the journal and the editor."

Chaimae Khairoun

The submission is very easy and the time from submission to response from the reviewers is short. Correspondence with the journal is nice and rapid.

Catrin Henriksson

The Clinical Journal of Obstetrics and Gynecology is an open access journal focused on scientific knowledge publication with emphasis laid on the fields of Gynecology and Obstetrics. Their services toward us have been encouraging through their kindness and respect. Great consideration has been given to us as young budding researchers and we are very grateful for this.

Carole Assontsa

During the process your positive communication, prompt feedback and professional approach is very highly appreciated. We would like to thank you very much for your support.

Can Vuran

I do appreciate for your service including submission, analysis, review, editorial and publishing process. I believe these esteemed journal enlighten the science with its high-quality personel.

Bora Uysal

I am very much pleased with the fast track publication by your reputed journal's editorial team. It is really helpful for researchers like me from developing nations. I strongly recommend your journal for publication.

Badri Kumar Gupta

It has been a fabulous journey writing articles for your journal because of the encouragement you people provide for writers from developing nations like India. Kindly continue the same. Looking forward for a long term association.

Badareesh Lakshminarayana

Many thanks for publishing my article in your great journal and the friendly and hassle-free publication process, the constructive peer-review, the regular feedback system, and the Quick response to any queries.

Azab Elsayed Azab

I would like to thank this journal for publishing my Research Article. Something I really appreciate about this journal is, they did not take much time from the day of Submission to the publishing date. Looking forward to have more publications in future.

Ayush Chandra

Submission of paper was smooth, the review process was fast. I had excellent communication and on time response from the editor.

Ayokunle Dada

Your service is very good and fast reply, also your service understand our situation and support us to publication our articles.

Ayman M Abu Mustafa

Really good service with prompt response. Looking forward to having long lasting relationship with your journal

Avishek Bagchi

Your service is excellent. Processing and editing were very fast. I hope to publish more of my works in your journal.

Ausraful Islam

I wanna to thank Clinical Journal of Nursing Care and Practice for its effort to review and publish my manuscript. This is reputable journal. Thank you!

Atsedemariam Andualem

“It was a delightful experience publishing my manuscript with the Clinical Journal of Obstetrics and Gynecology. They offered me lots of opportunities I never had from most publishing houses and their prompt services are greatly appreciated.”

Asafo Jones

I hope to ability to make some new investigation and publish in Your Company in future.

Artur Stopyra

I like the quality of the print & overall service. The paper looks quite impressive. Hope this will attract interested readers. All of you have our best wishes for continued success.

Arshad Khan

Your big support from researchers around the world is the best appreciation from your scientific teams. We believe that there should be no barrier in science and you make it real and this motto come true.

Arefhosseinir Rafi

Your journal co-operation is very appreciable and motivational. I am really thankful to your journal and team members for the motivation and collaboration to publish my work.

Assistant Professor, UCLAS Uttaranchal University, Dehradun, India

Archna Dhasmana

I am glad to submit the article to Heighten Science Publications as it has a very smooth and fast peer-review process, which enables the researchers to communicate their work on time.

Anupam M

This is to specify that I have had an extensive and detailed interaction with the Editorial team of Annals of Clinical Gastroenterology and Hepatology, USA, lasting over a significant period of time. My interaction has been extremely pleasant, especially with Ms Allie Smith, as I find the communication quite inspiring and crystal clear. The attitude of aforesaid individuals is quite helpful and guiding in pertinent instances. It has been a commemorative journey so far working with the Journal and I hope that the symbiosis will continue, evolve and flourish in the forthcoming years. I wish the journal, related personnel and aforementioned individuals a fruitful, successful run.

New Delhi, India

Anubha Bajaj

We appreciate the fact that you decided to give us full waiver for the applicable charges and approve the final version. You did an excellent job preparing the PDF version. Of course we will consider your magazine for our future submissions and we will pay the applicable fees then.

Anna Dionysopoulou

''Co-operation of Archives of Surgery and Clinical Research journal is appreciable. I'm impressed at the promptness of the publishing staff and the professionalism displayed. Thank you very much for your support, help and encouragement.''

Anıl Gokce

Congratulations for the excellence of your journal and high quality of its publications.

Angel MARTIN CASTELLANOS

The service from the journal staff has been excellent.

Andy Smith

I was very pleased with the quick editorial process. We are sure that our paper will have great visibility, among other things due to its open access. We believe in science accessible to all.

Anderson Fernando de Souza

It was a great experience publishing through JCICM. The article has reached out to several institutions. Appreciate your professional work. Hope to work with you again

Anas Wardeh

Publishing an article is a long process, but working with your publication department made things go smoothly, even though the process took exactly 5 months from the time of submitting the article till the time I have favourable response, the missing part is the peer review details, which is essential in self auditing and future improvement, overall experience was excellent giving your understanding of the situation of lack of financial institution support.

Anas Diab

I think that Heighpubs very good. You are very helpful. Thank you for everything.

Ana Ribeiro

Regarding to be services, we note that are work with high standards of professionalism translated into quick response, efficiency which makes communication accessible. Furthermore, I believe to be much inviting for the submission of future works for publication purposes.

Amélia João Alice Nkutxi

I would like to mention that I had a wonderful experience working with HSPI. The whole process right from manuscript submission to peer review till the publication of the article was very prompt & efficient. I wish you good luck for the future.

Amarjeet Gambhir

Once I submitted the manuscript, the response time of the reviewers was very fast. The fine-tuning of the galley proof was likewise prompt. I believe the journal provide a valuable outlet to disseminate physical rehabilitation scientific knowledge to the clinical community. Respectfully. Dr. Alon

Alon

We really appreciate and thanks the full waiver you provide for our article. We happy to publish our paper in your journal. Thank you very much for your good support and services.

Ali Abusafia

It was a real pleasure working with your team. The review was done fast, and it was very clear, the editing was flawless, the article was published quickly compared to other journals, and everyone was understanding and helpful. I will gladly recommend this journal to my acquaintances in academia.

Alexandra Cozma

To the editorial team at HSPI and the Journal of Clinical Nephrology: Thank you so much for your hard work and collaboration in bringing our article to life. Your staff was responsive, flexible, and communicative and made the process smooth and easy. Thank you!

Alejandro Munoz

Dear colleagues! I am satisfied with our cooperation with you. Your service is at a high level. I hope for a future relationship. Let me know if I can get a paper version of the magazine with my articles from you. I see them on the Internet.

Aksenov V.V

"This is my first time publishing with the journal/publisher. I am impressed at the promptness of the publishing staff and the professionalism displayed. Thank you for encouraging young researchers like me!"

Ajite Kayode

I want to thank you for our collaboration. You were fast and effective with a positive spirit of teamwork. I am truly excited from our collaboration. You were like always fast, efficient and accurate. I hope that in the near future we will collaborate again.

Aikaterini Solomou

In my opinion, you provide a very fast and practical service.

Ahmet Eroglu

Great, We are too comfortable with the process including the peer review process and quality. But, the journal should be indexed in different databases such scopus.

Afework Edmealem

We really appreciate your efforts towards our article, the professional way you handle our request for exemption from charges. It was a great honor for us to publish in your magazine.

Achraf elbakkaly

I really liked the ease of submitting my manuscript in the HSPI journal. Further, the peer review was timely completed and I was communicated the final decision on my manuscript within 10 days of submission which is really appreciable. I strongly recommend all the scientists and researchers to submit their work in this journal”

Abu Bashar

My candid opinion is that the service you render is second to none. My favourite part is the prompt response to issue, really i value that.

Abiodun Akanbi Adeogun

Thank you very much for accepting our manuscript in your journal “International Journal of Clinical Virology”. We are very thankful to the esteemed team for timely response and quick review process. The editorial team of International Journal of Clinical Virology is too cooperative and well-mannered during the publication process. We are hopeful to publish many quality papers in your journal and I suggest the International Journal of Clinical Virology to all of my colleagues, researchers and friends to publish their research here.

Abdul Baset

I, Muhammad Sarwar Khan, am serving as Editor on Archives of Biotechnology and Biomedicine (ABB). I submitted an editorial titled, 'Edible vaccines to combat Infectious Bursal Disease of poultry' for publication in ABB. After submitting the manuscript; the services rendered by the management and technical personnel to handle and process the manuscript were marvelous. Plagiarism report was shared with me with complements before reviewers' comments, All steps including article processing and service charges were well taken care of keeping in view the author's interest/preference. All together, it was an encouraging and wonderful experience working with ABB personnel.

University of Agriculture, Pakistan

Muhammad Sarwar Khan

Your journal has accomplished its intended mission of providing very effective and efficient goals in dealing with submissions, conducting the reviewing process and in publishing accepted manuscripts in a timely manner. Keep up the great work and services that you provide.

University of Jacqmar, Inc., USA

John St. Cyr

I am to express my view that Heighten Science Publications are reliable quick even after peer review process. I hope and wish the publications will go a long way in disseminating science to many interested in scientific research.

College of Fisheries, CAU(I), Tripura, India

Ajit Kumar Roy

The Journal Clinical Nephrology provides a good opportunity for readers to stay updated in the field of clinical nephrology. Additionally - it provides a good opportunity for authors to publish their work. 1. Publication of the accepted manuscripts is sufficiently rapid. 2. The trust factor between the journal and me, as an author, is very important and well preserved. 3. Peer review process very rapid and effective.

Assaf Harofeh Medical Center, Israel

Leonid Feldman

In 2017, I submitted a manuscript to the journal Archives of Biotechnology and Biomedicine belonging to Heighten Science Publications Corporation. Within one week I already received the response from the editor. All processing steps were really fast so in terms of a speedy publication I can particularly recommend the journal Archives of Biotechnology and Biomedicine. The responsible contact person of the journal was always available, which gives a trustworthy impression to the author. Also the peer review process was clear and constructive. So from my experience with Heighten Science Publications Corporation I can recommend publishing there.

University of Tubingen, Germany

Yvonne Mast

We thank to the heighten science family, who speed up the publication of our article and provide every support.

Mehmet Besir

The services of the journal were excellent. The most important thing for an author is the speed of the peer review which was really fast here. They returned in a few days and immediately replied all of my questions. I want to refer this platform to all scholars. Many thanks.

Eastern Mediterranean University, Cyprus

Zehra Guchan TOPCU

Thank you for your attitude and support. I am sincerely grateful to you and the entire staff of the magazine for the high professionalism and fast quality work. Thank you very much!

USA

Igor Klepikov

Thank you and your company for effective support of authors which are very much dependable on the funds gambling for science in the different countries of our huge and unpredictable world. We are doing our work and should rely on a teams like Galley Proof-HSPC. Great success to all of you for the 2019th! Be well all the year long.

Russia

Victor V Apollonov

The editorial process was quickly done. The galley proof was sent within a week after being accepted for publication. The editorial team was very helpful and responded promptly.

India

Rohit Kulshrestha

Publishing with the International Journal of Clinical and Experimental Ophthalmology was a rewarding experience as review process was thorough and brisk. Their visibility online is second to none as their published articles appear in all search engines. I will encourage researchers to publish with them.

University of Port Harcourt Teaching Hospital, Nigeria

Dr. Elizabeth A Awoyesuku

"It was a pleasure to work with the editorial team of the journal on the submission of the manuscript. The team was professional, fast, and to the point".

NC A&T State University, USA

Moran Sciamama-Saghiv

Submission of paper was smooth, the review process was fast. I had excellent communication and on time response from the editor.

Ekiti State University Teaching Hospital, Nigeria

Ayokunle Dada

I am delighted and satisfied with. Heighten Science Publications as my manuscript was thoroughly assessed and published on time without delay. Keep up the good work.

Ido-Ekiti/Afe Babalola University, Nigeria

Dr. Shuaib Kayode Aremu

"This is my first time publishing with the journal/publisher. I am impressed at the promptness of the publishing staff and the professionalism displayed. Thank you for encouraging young researchers like me!"

Ekiti State University, Nigeria

Adebukola Ajite

I wanna to thank clinical journal of nursing care and practice for its effort to review and publish my manuscript. This is reputable journal. Thank you!

Wollo University, Ethiopia

Atsedemariam Andualem

We appreciate your approach to scholars and will encourage you to collaborate with your organization, which includes interesting and different medical journals. With the best wishes of success, creativity and joy in life, prosperity in the medical field.

Ivano- Frankivsk National Medical University, Ukraine

Nataliya Kitsera

Thank you very much for your support and encouragement. I am truly impressed by your tolerance and support. Thank you very much

Diaverum: PADC, Jeddah, Saudi Arabia

Nasrulla Abutaleb

You are such a nice person. Your journal co-operation is very appreciable and motivational.

Department of Biotechnology, Uttaranchal college of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, India

Archna Dhasmana

“Mobile apps and wearable technology are becoming ubiquitous in our environment. Their integration with healthcare delivery is just beginning to take shape. The early results are promising and the possibilities great."

BS, PharmD., MBA, CPHIMS, FHIMSS, Adjunct Professor, Global Healthcare Management, MCPHS University, Chief Strategy Offi cer, MedicaSoft, Senior Advisor, National Health IT (NHIT) Collaborative for Underserved, New York HIMSS, National Liaison, Health 2.0 Boston, Past Chair, Chair Innovation, USA

Helen Figge

“The choice to submit the forensic case study to the Journal of Addiction Therapy and Research was dictated by the match between the content and the potential readership. The publication process proved to be expedient and we were provided with constructive feedback from reviewers. The final article layout is attractive and conforms to standards. All-in-all, it has been a rewarding process.”

Ph.D, Boston University Department of Communication Sciences and Disorders and Knowledge Research Institute, Inc., 2131 Reflection Bay Drive, Arlington, Texas 76013, USA

Elisabeth H. Wiig

The service is nice and the time of processing the application is fast.

Department of Neurosurgery, Queen Elizabeth Hospital, Hong Kong

Long Ching

Your service is very good and fast reply, Also your service understand our situation and support us to publication our articles.

Palestine College of Nursing, Khan Younis, Gaza Strip, Palestine

Ayman M Abu Mustafa

“It was a delightful experience publishing my manuscript with the Clinical Journal of Obstetrics and Gynecology. They offered me lots of opportunities I never had from most publishing houses and their prompt services are greatly appreciated.”

Department of Agricultural Economics, Agribusiness and Extension, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana

Akowuah Jones Asafo

View More

Related Journals

Help ?