Mechanosensitive Differentiation of Human iPS Cell-Derived Podocytes
Stem cell fate decisions, including proliferation, differentiation, morphological changes, and viability, are impacted by microenvironmental cues such as physical and biochemical signals. However, the specific impact of matrix elasticity on kidney cell development and function remains less understoo...
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MDPI AG
2024-10-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/11/10/1038 |
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| author | Yize Zhang Samira Musah |
| author_facet | Yize Zhang Samira Musah |
| author_sort | Yize Zhang |
| collection | DOAJ |
| description | Stem cell fate decisions, including proliferation, differentiation, morphological changes, and viability, are impacted by microenvironmental cues such as physical and biochemical signals. However, the specific impact of matrix elasticity on kidney cell development and function remains less understood due to the lack of models that can closely recapitulate human kidney biology. An established protocol to differentiate podocytes from human-induced pluripotent stem (iPS) cells provides a promising avenue to elucidate the role of matrix elasticity in kidney tissue development and lineage determination. In this study, we synthesized polyacrylamide hydrogels with different stiffnesses and investigated their ability to promote podocyte differentiation and biomolecular characteristics. We found that 3 kPa and 10 kPa hydrogels significantly support the adhesion, differentiation, and viability of podocytes. Differentiating podocytes on a more compliant (0.7 kPa) hydrogel resulted in significant cell loss and detachment. Further investigation of the mechanosensitive proteins yes-associated protein (YAP) and synaptopodin revealed nuanced molecular distinctions in cellular responses to matrix elasticity that may otherwise be overlooked if morphology and cell spreading alone were used as the primary metric for selecting matrices for podocyte differentiation. Specifically, hydrogels with kidney-like rigidities outperformed traditional tissue culture plates at modulating the molecular-level expression of active mechanosensitive proteins critical for podocyte health and function. These findings could guide the development of physiologically relevant platforms for kidney tissue engineering, disease modeling, and mechanistic studies of organ physiology and pathophysiology. Such advances are critical for realizing the full potential of in vitro platforms in accurately predicting human biological responses. |
| format | Article |
| id | doaj-art-95d10a3e07d24b8088bd1b8f2147a148 |
| institution | OA Journals |
| issn | 2306-5354 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
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| series | Bioengineering |
| spelling | doaj-art-95d10a3e07d24b8088bd1b8f2147a1482025-08-20T02:11:12ZengMDPI AGBioengineering2306-53542024-10-011110103810.3390/bioengineering11101038Mechanosensitive Differentiation of Human iPS Cell-Derived PodocytesYize Zhang0Samira Musah1Department of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USADepartment of Biomedical Engineering, Pratt School of Engineering, Duke University, Durham, NC 27708, USAStem cell fate decisions, including proliferation, differentiation, morphological changes, and viability, are impacted by microenvironmental cues such as physical and biochemical signals. However, the specific impact of matrix elasticity on kidney cell development and function remains less understood due to the lack of models that can closely recapitulate human kidney biology. An established protocol to differentiate podocytes from human-induced pluripotent stem (iPS) cells provides a promising avenue to elucidate the role of matrix elasticity in kidney tissue development and lineage determination. In this study, we synthesized polyacrylamide hydrogels with different stiffnesses and investigated their ability to promote podocyte differentiation and biomolecular characteristics. We found that 3 kPa and 10 kPa hydrogels significantly support the adhesion, differentiation, and viability of podocytes. Differentiating podocytes on a more compliant (0.7 kPa) hydrogel resulted in significant cell loss and detachment. Further investigation of the mechanosensitive proteins yes-associated protein (YAP) and synaptopodin revealed nuanced molecular distinctions in cellular responses to matrix elasticity that may otherwise be overlooked if morphology and cell spreading alone were used as the primary metric for selecting matrices for podocyte differentiation. Specifically, hydrogels with kidney-like rigidities outperformed traditional tissue culture plates at modulating the molecular-level expression of active mechanosensitive proteins critical for podocyte health and function. These findings could guide the development of physiologically relevant platforms for kidney tissue engineering, disease modeling, and mechanistic studies of organ physiology and pathophysiology. Such advances are critical for realizing the full potential of in vitro platforms in accurately predicting human biological responses.https://www.mdpi.com/2306-5354/11/10/1038human-induced pluripotent stem cellsstem cell differentiationpodocytesmechanobiologybiomaterialsmatrix elasticity |
| spellingShingle | Yize Zhang Samira Musah Mechanosensitive Differentiation of Human iPS Cell-Derived Podocytes Bioengineering human-induced pluripotent stem cells stem cell differentiation podocytes mechanobiology biomaterials matrix elasticity |
| title | Mechanosensitive Differentiation of Human iPS Cell-Derived Podocytes |
| title_full | Mechanosensitive Differentiation of Human iPS Cell-Derived Podocytes |
| title_fullStr | Mechanosensitive Differentiation of Human iPS Cell-Derived Podocytes |
| title_full_unstemmed | Mechanosensitive Differentiation of Human iPS Cell-Derived Podocytes |
| title_short | Mechanosensitive Differentiation of Human iPS Cell-Derived Podocytes |
| title_sort | mechanosensitive differentiation of human ips cell derived podocytes |
| topic | human-induced pluripotent stem cells stem cell differentiation podocytes mechanobiology biomaterials matrix elasticity |
| url | https://www.mdpi.com/2306-5354/11/10/1038 |
| work_keys_str_mv | AT yizezhang mechanosensitivedifferentiationofhumanipscellderivedpodocytes AT samiramusah mechanosensitivedifferentiationofhumanipscellderivedpodocytes |