Abstract
Purpose: The embryonic microenvironment contains many properties that have not yet been fully explored. Our aim in this study is to report an optimized and efficient method that enables investigating the effects of the secretome of pluripotent embryonic stem cells on cancer stem cells.
Methods: The study is performed with a chimeric model consisted of mouse blastocysts, human prostate cancer stem cells and non-cancer stem cells. Ovulation induced mice were used for blastocyst collection. DU145 prostate cancer cell line was separated into cancer stem cells and non-cancer stem cells according to cancer stem cells biomarker expressions by fluorescent activated cell sorting method. Human prostate cancer stem cells and non-cancer stem cells were microinjected into 4-day blastocyst culture in vitro by intracytoplasmic sperm injection method.
Results: Chimeric models provide us great convenience in basic oncological studies. In this study, using a chimeric model, we were able to study the secretome of mouse embryonic stem cells and their effect on cancer stem cells. The method is efficient and yield promising result; and could be used to study the effects on other cells as well.
Conclusion: The embryonic stem cell microenvironment is suggested to have a great regenerative capacity which is, nowadays, the center of attraction for cancer research studies. Ethical issues restrict the human embryo studies, however, mimicking the in vivo human microenvironment with 3D cell cultures or bioprinting are now possible. Finally, optimization of new methods including 3D cell cultures with human cell lines will be a great opportunity for better understanding the reprogramming notion.
Keywords
Cancer stem cells embryonic stem cells induced pluripotent stem cells microenvironment secretome intracytoplasmic sperm injection
Supporting Institution
-
Project Number
-
Thanks
-
References
- 1. Baran ÖP, Nergiz Y and Bahçeci S: Göbek Kordonu Kan ve Stromal Kökenli Hücrelerin Sinir Hücrelerine Farklılaşması Differentiation of Human Cord Blood and Stromal Derived Stem Cells into Neuron Cells. 233–238, 2007.
- 2. Plast VE, Nde TES and Kavramlar N: 7. Enver Tali ÇET N Konferansı. 20: 1–8, 2006.
- 3. Günefl AM: Kök Hücre Plastisitesi ve T › ptaki Kullan › m Alanlar ›. 36–42.
- 4. Martin GR: Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78: 7634–7638, 1981.
- 5. Smith AG: Embryo-Derived Stem Cells: Of Mice and Men. http://dx.doi.org/101146/annurev.cellbio171435 17: 435–462, 2003 . 6. Sağlık Araştırma Enstitüsü Ottawa Hastanesi O: İnsan Embriyonik Kök Hücreleri İzolasyon, İdame ve Farklılaşma (diferansiyasyon) Kürşad TÜRKŞEN.
- 7. Abbott DE, Bailey CM, Postovit LM, Seftor EA, Margaryan N, Seftor REB and Hendrix MJC: The Epigenetic Influence of Tumor and Embryonic Microenvironments: How Different are They? Cancer Microenviron 1: 13, 2008.
- 8. Zhou S, Abdouh M, Arena V, Arena M and Arena GO: Reprogramming malignant cancer cells toward a benign phenotype following exposure to human embryonic stem cell microenvironment. PLoS One 12, 2017.
- 9. Deftu AT, Radu BM, Cretoiu D, Deftu AF, Cretoiu SM and Xiao J: Exosomes as intercellular communication messengers for cardiovascular and cerebrovascular diseases. Exosomes: 199–238, 2020.
- 10. De Toro J, Herschlik L, Waldner C and Mongini C: Emerging Roles of Exosomes in Normal and Pathological Conditions: New Insights for Diagnosis and Therapeutic Applications. Front Immunol 6, 2015.
- 11. Wortzel I, Dror S, Kenific CM and Lyden D: Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell 49: 347–360, 2019.
- 12. Falcone G, Felsani A and D’Agnano I: Signaling by exosomal microRNAs in cancer. J Exp Clin Cancer Res 34: 1–10, 2015.
- 13. Minciacchi VR, Freeman MR and Di Vizio D: Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes. Semin Cell Dev Biol 40: 41–51, 2015.
- 14. van der Pol E, Böing AN, Harrison P, Sturk A and Nieuwland R: Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64: 676–705, 2012.
- 15. Greening DW, Gopal SK, Mathias RA, Liu L, Sheng J, Zhu HJ and Simpson RJ: Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression. Semin Cell Dev Biol 40: 60–71, 2015.
- 16. Singh A and Settleman J: EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29: 4741, 2010.
- 17. Kelekçi S, Uğurlu-Çimen D, Demir AB, et al.: Generation of transgene-free iPSC lines from three patients with Friedreich’s ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene. Stem Cell Res 54, 2021.
- 18. Akbari S, Sevinç GG, Ersoy N, et al.: Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling. Stem Cell Reports 13: 627–641, 2019.
- 19. Desai N, Rambhia P and Gishto A: Human embryonic stem cell cultivation: Historical perspective and evolution of xeno-free culture systems. Reprod Biol Endocrinol 13: 1–15, 2015.
- 20. Mackinlay KML, Weatherbee BAT, Rosa VS, et al.: An in vitro stem cell model of human epiblast and yolk sac interaction. Elife 10: 1–28, 2021.
- 21. Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M and Stojkovic M: Derivation of human embryonic stem cells from developing and arrested embryos. Stem Cells 24: 2669–2676, 2006.
- 22. Reubinoff BE, Pera MF, Fong CY, Trounson A and Bongso A: Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18: 399–404, 2000.
- 23. JA T, J I-E, SS S, MA W, JJ S, VS M and JM J: Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147, 1998.
- 24. Meyer JR: The significance of induced pluripotent stem cells for basic research and clinical therapy. J Med Ethics 34: 849–851, 2008.
Abstract
Project Number
-
References
- 1. Baran ÖP, Nergiz Y and Bahçeci S: Göbek Kordonu Kan ve Stromal Kökenli Hücrelerin Sinir Hücrelerine Farklılaşması Differentiation of Human Cord Blood and Stromal Derived Stem Cells into Neuron Cells. 233–238, 2007.
- 2. Plast VE, Nde TES and Kavramlar N: 7. Enver Tali ÇET N Konferansı. 20: 1–8, 2006.
- 3. Günefl AM: Kök Hücre Plastisitesi ve T › ptaki Kullan › m Alanlar ›. 36–42.
- 4. Martin GR: Isolation of a pluripotent cell line from early mouse embryos cultured in medium conditioned by teratocarcinoma stem cells. Proc Natl Acad Sci U S A 78: 7634–7638, 1981.
- 5. Smith AG: Embryo-Derived Stem Cells: Of Mice and Men. http://dx.doi.org/101146/annurev.cellbio171435 17: 435–462, 2003 . 6. Sağlık Araştırma Enstitüsü Ottawa Hastanesi O: İnsan Embriyonik Kök Hücreleri İzolasyon, İdame ve Farklılaşma (diferansiyasyon) Kürşad TÜRKŞEN.
- 7. Abbott DE, Bailey CM, Postovit LM, Seftor EA, Margaryan N, Seftor REB and Hendrix MJC: The Epigenetic Influence of Tumor and Embryonic Microenvironments: How Different are They? Cancer Microenviron 1: 13, 2008.
- 8. Zhou S, Abdouh M, Arena V, Arena M and Arena GO: Reprogramming malignant cancer cells toward a benign phenotype following exposure to human embryonic stem cell microenvironment. PLoS One 12, 2017.
- 9. Deftu AT, Radu BM, Cretoiu D, Deftu AF, Cretoiu SM and Xiao J: Exosomes as intercellular communication messengers for cardiovascular and cerebrovascular diseases. Exosomes: 199–238, 2020.
- 10. De Toro J, Herschlik L, Waldner C and Mongini C: Emerging Roles of Exosomes in Normal and Pathological Conditions: New Insights for Diagnosis and Therapeutic Applications. Front Immunol 6, 2015.
- 11. Wortzel I, Dror S, Kenific CM and Lyden D: Exosome-Mediated Metastasis: Communication from a Distance. Dev Cell 49: 347–360, 2019.
- 12. Falcone G, Felsani A and D’Agnano I: Signaling by exosomal microRNAs in cancer. J Exp Clin Cancer Res 34: 1–10, 2015.
- 13. Minciacchi VR, Freeman MR and Di Vizio D: Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes. Semin Cell Dev Biol 40: 41–51, 2015.
- 14. van der Pol E, Böing AN, Harrison P, Sturk A and Nieuwland R: Classification, functions, and clinical relevance of extracellular vesicles. Pharmacol Rev 64: 676–705, 2012.
- 15. Greening DW, Gopal SK, Mathias RA, Liu L, Sheng J, Zhu HJ and Simpson RJ: Emerging roles of exosomes during epithelial-mesenchymal transition and cancer progression. Semin Cell Dev Biol 40: 60–71, 2015.
- 16. Singh A and Settleman J: EMT, cancer stem cells and drug resistance: an emerging axis of evil in the war on cancer. Oncogene 29: 4741, 2010.
- 17. Kelekçi S, Uğurlu-Çimen D, Demir AB, et al.: Generation of transgene-free iPSC lines from three patients with Friedreich’s ataxia (FRDA) carrying GAA triplet expansions in the first intron of FXN gene. Stem Cell Res 54, 2021.
- 18. Akbari S, Sevinç GG, Ersoy N, et al.: Robust, Long-Term Culture of Endoderm-Derived Hepatic Organoids for Disease Modeling. Stem Cell Reports 13: 627–641, 2019.
- 19. Desai N, Rambhia P and Gishto A: Human embryonic stem cell cultivation: Historical perspective and evolution of xeno-free culture systems. Reprod Biol Endocrinol 13: 1–15, 2015.
- 20. Mackinlay KML, Weatherbee BAT, Rosa VS, et al.: An in vitro stem cell model of human epiblast and yolk sac interaction. Elife 10: 1–28, 2021.
- 21. Zhang X, Stojkovic P, Przyborski S, Cooke M, Armstrong L, Lako M and Stojkovic M: Derivation of human embryonic stem cells from developing and arrested embryos. Stem Cells 24: 2669–2676, 2006.
- 22. Reubinoff BE, Pera MF, Fong CY, Trounson A and Bongso A: Embryonic stem cell lines from human blastocysts: somatic differentiation in vitro. Nat Biotechnol 18: 399–404, 2000.
- 23. JA T, J I-E, SS S, MA W, JJ S, VS M and JM J: Embryonic stem cell lines derived from human blastocysts. Science 282: 1145–1147, 1998.
- 24. Meyer JR: The significance of induced pluripotent stem cells for basic research and clinical therapy. J Med Ethics 34: 849–851, 2008.
Details
| Primary Language | English |
|---|---|
| Subjects | Health Care Administration |
| Journal Section | Research Article |
| Authors | |
| Project Number | - |
| Publication Date | January 31, 2023 |
| Submission Date | July 1, 2022 |
| Published in Issue | Year 2023 Volume: 7 Issue: 1 |
