TY - JOUR
T1 - Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation
AU - Liu, Naiyou
AU - Bowen, Charles M.
AU - Shoja, Mohammadali M.
AU - Castro de Pereira, Karen Larissa
AU - Dongur, Laxmi Priya
AU - Saad, Antonio
AU - Russell, William K.
AU - Broderick, Thomas Christopher
AU - Fair, Jeffrey H.
AU - Fagg, William Samuel
N1 - Funding Information:
T.C.B. and W.S.F. are co-founders and shareholders in Merakris Therapeutics, and J.H.F. was the recipient of sponsored project funds by Merakris Therapeutics that supported in part some of the research contained herein.
Funding Information:
We thank our funding sources Mimmie and Halley Smith Endowments to J.H.F. and W.S.F., the John L. Hearn Chair of Transplant Endowment to J.H.F., and grant funding from the NIH NCATS CTSA KL2 KL2TR001441 to W.S.F., UTMB Department of Surgery Pilot Project funding to W.S.F., and NIH NIDDK 5T32DK007639 to J.H.F., W.K.R. and the UTMB Mass Spectrometry Facility receives support from Cancer Prevention Research Institute of Texas (CPRIT) grant number RP190682.
Publisher Copyright:
© 2022 by the authors.
PY - 2022/9
Y1 - 2022/9
N2 - 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.
AB - 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.
KW - amniotic fluid
KW - epithelial–mesenchymal transition
KW - myofibroblast
KW - regenerative medicine
KW - stem cells
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U2 - 10.3390/biomedicines10092189
DO - 10.3390/biomedicines10092189
M3 - Article
AN - SCOPUS:85138660360
VL - 10
JO - Biomedicines
JF - Biomedicines
SN - 2227-9059
IS - 9
M1 - 2189
ER -