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Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation
Published on: June 17, 2015
Studying the Toxic Effects of Some Biologically Active Peptides on the Model of Mouse Embryonic Stem Cells
A G Kobylyanskii1, Yu A Zolotarev2, L A Andreeva2
1Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, Russia. testers@yandex.ru.
Abstract:
We studied the effects of peptide drugs (HLDF-6, PGP, RPGP, and PGLP) and peptide pharmaceutical products (Semax, Selank, and thyroliberin) on proliferation and survival of mouse embryonic stem cells and their derivatives. Differentiation of mouse embryonic stem cells into neuronal precursors was evaluated. PGP and PGLP in concentrations of 10 and 0.1 μM, respectively, had little, but significant inhibitory effect on proliferative activity of cells. These peptides in concentrations of 10 and 0.1 μM, respectively, and Semax (10 and 0.1 μM) significantly increased the survival rate of mouse embryonic stem cells (serum deprivation). Moreover, study peptides had little effect on the formation of neuronal precursors from mouse embryonic stem cells. HLDF-6, Selank, and thyroliberin produced an insignificant effect on the differentiation of these cells into mature neurons. Analysis of differentiation of embryonic stem cells into GABA+ neurons showed that Selank, thyroliberin (100 μM), and NGF (100 ng/ml) decrease the ratio of these cells by 61, 58, and 87%, respectively, in comparison with the control. Our results indicate that these peptide compounds do not produce toxic effect during the embryonic and fetal period of life.
Insights
Peptide drugs like PGP and PGLP slightly inhibited mouse embryonic stem cell proliferation but enhanced survival. These compounds, along with Semax, showed minimal impact on neuronal differentiation, indicating no embryonic toxicity.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Embryonic stem cells (ESCs) are crucial for developmental studies.
- Peptide drugs offer therapeutic potential but require safety evaluation.
- Understanding peptide effects on ESCs is vital for regenerative medicine.
Purpose of the Study:
- To investigate the impact of specific peptide drugs and pharmaceutical products on mouse ESC proliferation, survival, and neuronal differentiation.
- To assess the potential toxicity of these peptides during early developmental stages.
Main Methods:
- Mouse ESCs were treated with various peptide drugs (HLDF-6, PGP, RPGP, PGLP) and pharmaceutical products (Semax, Selank, thyroliberin) at different concentrations.
- Cell proliferation and survival rates were measured, particularly under serum deprivation.
- Differentiation into neuronal precursors and mature neurons (including GABA+ neurons) was evaluated.
Main Results:
- PGP and PGLP exhibited minor inhibitory effects on cell proliferation.
- PGP, PGLP, and Semax significantly enhanced ESC survival during serum deprivation.
- Most peptides had minimal effects on neuronal precursor formation and differentiation into mature neurons.
- Selank, thyroliberin, and NGF notably decreased the proportion of GABA+ neurons.
Conclusions:
- The studied peptide compounds do not exhibit significant toxicity to mouse ESCs during embryonic and fetal developmental periods.
- Specific peptides demonstrate potential for enhancing ESC survival, while neuronal differentiation effects vary.
- Further research is warranted to explore the therapeutic applications of these peptides in neurodevelopment and regenerative medicine.
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