Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation
Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent my...
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| Format: | Article |
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MDPI AG
2022-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/9/2189 |
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| author | Naiyou Liu Charles M. Bowen Mohammadali M. Shoja Karen Larissa Castro de Pereira Laxmi Priya Dongur Antonio Saad William K. Russell Thomas Christopher Broderick Jeffrey H. Fair William Samuel Fagg |
| author_facet | Naiyou Liu Charles M. Bowen Mohammadali M. Shoja Karen Larissa Castro de Pereira Laxmi Priya Dongur Antonio Saad William K. Russell Thomas Christopher Broderick Jeffrey H. Fair William Samuel Fagg |
| author_sort | Naiyou Liu |
| collection | DOAJ |
| description | Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we discovered that co-cultured amniotic cell conditioned media (coACCM) and AF have opposing effects on myofibroblast activation: coACCM activates the epithelial–mesenchymal transition (EMT) and stimulates gene expression patterns associated with myofibroblast activation, while AF does the opposite. Intriguingly, extracellular vesicles (EVs) purified from AF are necessary and sufficient to activate EMT and inflammatory gene expression patterns, while the EV-depleted AF potently represses these responses. In summary, these data indicate that coACCM stimulates myofibroblast activation, while AF represses it. We interpret these findings to suggest that coACCM, AF, and fractionated AF represent unique biologics that elicit different cellular responses that are correlated with a wide variety of pathological states, and therefore could have broad utility in the clinic and the lab. |
| first_indexed | 2024-03-10T00:38:57Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:38:57Z |
| publishDate | 2022-09-01 |
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| series | Biomedicines |
| spelling | doaj.art-160600e18f9c4032a8d0b026591177b92023-11-23T15:10:38ZengMDPI AGBiomedicines2227-90592022-09-01109218910.3390/biomedicines10092189Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast ActivationNaiyou Liu0Charles M. Bowen1Mohammadali M. Shoja2Karen Larissa Castro de Pereira3Laxmi Priya Dongur4Antonio Saad5William K. Russell6Thomas Christopher Broderick7Jeffrey H. Fair8William Samuel Fagg9Division of Transplant, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADivision of Transplant, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADivision of Transplant, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADivision of Transplant, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADivision of Transplant, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX 77555, USADepartment of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USAMerakris Therapeutics, RTP Frontier, Research Triangle Park, NC 27709, USADivision of Transplant, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USADivision of Transplant, Department of Surgery, University of Texas Medical Branch, Galveston, TX 77555, USAMyofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we discovered that co-cultured amniotic cell conditioned media (coACCM) and AF have opposing effects on myofibroblast activation: coACCM activates the epithelial–mesenchymal transition (EMT) and stimulates gene expression patterns associated with myofibroblast activation, while AF does the opposite. Intriguingly, extracellular vesicles (EVs) purified from AF are necessary and sufficient to activate EMT and inflammatory gene expression patterns, while the EV-depleted AF potently represses these responses. In summary, these data indicate that coACCM stimulates myofibroblast activation, while AF represses it. We interpret these findings to suggest that coACCM, AF, and fractionated AF represent unique biologics that elicit different cellular responses that are correlated with a wide variety of pathological states, and therefore could have broad utility in the clinic and the lab.https://www.mdpi.com/2227-9059/10/9/2189myofibroblastamniotic fluidregenerative medicineepithelial–mesenchymal transitionstem cells |
| spellingShingle | Naiyou Liu Charles M. Bowen Mohammadali M. Shoja Karen Larissa Castro de Pereira Laxmi Priya Dongur Antonio Saad William K. Russell Thomas Christopher Broderick Jeffrey H. Fair William Samuel Fagg Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation Biomedicines myofibroblast amniotic fluid regenerative medicine epithelial–mesenchymal transition stem cells |
| title | Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation |
| title_full | Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation |
| title_fullStr | Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation |
| title_full_unstemmed | Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation |
| title_short | Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation |
| title_sort | comparative analysis of co cultured amniotic cell conditioned media with cell free amniotic fluid reveals differential effects on epithelial mesenchymal transition and myofibroblast activation |
| topic | myofibroblast amniotic fluid regenerative medicine epithelial–mesenchymal transition stem cells |
| url | https://www.mdpi.com/2227-9059/10/9/2189 |
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