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Promoting Maturation of Human Pluripotent Stem Cell-Derived Renal Microtissue by Incorporation of Endothelial and Mesenchymal Cells
Abstract
Directed differentiation of human pluripotent stem cells (hPSCs) uses a growing number of small molecules and growth factors required for in vitro generation of renal lineage cells. Although current protocols are relatively inefficient or expensive. The first objective of the present work was to establish a new differentiation protocol for generating renal precursors. We sought to determine if inducer of definitive endoderm 1 (IDE1), a cost-effective small molecule, can be used to replace activin A. Gene expression data showed significantly increased expressions of nephrogenic markers in cells differentiated with 20 nM IDE1 compared with cells differentiated with activin A. Thus, renal lineage cells could be generated by this alternative approach. Afterward, we determined whether coculture of endothelial and mesenchymal cells could increase the maturation of three-dimensional (3D) renal structures. For this purpose, we employed a 3D coculture system in which hPSC-derived kidney precursors were cocultured with endothelial cells (ECs) and mesenchymal stem cells (MSCs), hereafter named RMEM (renal microtissue derived from coculture of renal precursors with endothelial and mesenchymal stem cells). hPSC-derived kidney precursors were cultured either alone [renal microtissue (RM)] or in coculture with human umbilical vein endothelial cells and human bone marrow-derived mesenchymal stem cells at an approximate ratio of 10:7:2, respectively. Immunofluorescent staining showed expressi…
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“As an illustration, potent mutagenic carcinogens like N-methyl-N-nitrosourea (MNU) and benzo(a)pyrene [141] have been demonstrated to be effective agents for immortalization in Syrian hamster dermal cells [142] cell transformation assay [143] through the direct inactivation of the tumor suppressors p53 and p16 (Figure 4) [144].”
From Cell Immortality: In Vitro Effective Techniques to Achieve and Investigate Its Applications and Challenges (2024) · cites this paper as [142]
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Cited by
Chalak, M., Hesaraki, M., Mirbahari, S. N., Yeganeh, M., Abdi, S., Rajabi, S., & Hemmatzadeh, F. (2024) · Life · doi:10.3390/life14030417 · Cited by 66
Metadata
- Authors
- Khoshdel-Rad, N., Zahmatkesh, E., Moeinvaziri, F., Haghparast, N., Baharvand, H., Aghdami, N., & Moghadasali, R.
- Affiliations
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
- Venue
- Stem Cells and Development
- Publisher
- SAGE Publications
- Published
- 2021-04-15
- Volume
- 30
- Issue
- 8
- Pages
- 428-440
- ISSN
- 1547-3287
- 1557-8534
- Cited by
- 13
- References
- 3
- Language
- en
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- Khoshdel-Rad, N., Zahmatkesh, E., Moeinvaziri, F., Haghparast, N., Baharvand, H., Aghdami, N., & Moghadasali, R. (2021). Promoting Maturation of Human Pluripotent Stem Cell-Derived Renal Microtissue by Incorporation of Endothelial and Mesenchymal Cells. Stem Cells and Development. https://doi.org/10.1089/scd.2020.0189