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Published on: June 3, 2018
Reversal of myofibroblasts by amniotic membrane stromal extract
Wei Li1, Hua He, Ying-Ting Chen
1TissueTech, Inc., Miami, Florida, USA.
Abstract:
Myofibroblasts play an important role in morphogenesis, inflammation, and fibrosis in most tissues. The amniotic membrane stroma can maintain keratocytes in cultures and prevent them from differentiating into myofibroblasts. However, it is unknown whether the AM stroma can also reverse differentiated myofibroblasts. In this study, we found that amniotic membrane stromal cells (AMSCs), which adopted fibroblastic phenotype in vivo, quickly and completely differentiated into myofibroblasts during ex vivo culture in DMEM/FBS on plastic within 2 passages. When cultured on type I collagen, the myofibroblasts maintained their phenotype, however, when these myofibroblasts were re-seeded onto a cryopreserved amniotic membrane stromal surface, they reversed to the fibroblast phenotype. Moreover, we found that the amniotic membrane stromal extract not only helps maintain primary AMSCs fibroblastic phenotype in vitro, but also can reverse differentiated myofibroblasts back to fibroblasts. This reversal was not coupled with cell proliferation. We concluded that the amniotic membrane stroma contains soluble factors that can regulate the mesenchymal cell differentiation. Further investigation into the identity of these factors and the control mechanisms may unravel a new scar-reversing strategy.
Insights
Amniotic membrane stroma can reverse differentiated myofibroblasts back into fibroblasts. This discovery suggests soluble factors within the stroma may offer new strategies for scar reversal and tissue regeneration.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Tissue Engineering
Background:
- Myofibroblasts are crucial in tissue repair but also implicated in fibrosis.
- The amniotic membrane stroma supports keratocyte maintenance, preventing myofibroblast differentiation.
- The potential of amniotic membrane stroma to reverse existing myofibroblast differentiation remains unexplored.
Purpose of the Study:
- To investigate whether amniotic membrane stroma can reverse differentiated myofibroblasts into fibroblasts.
- To identify soluble factors within the amniotic membrane stroma that regulate mesenchymal cell differentiation.
Main Methods:
- Culturing amniotic membrane stromal cells (AMSCs) ex vivo to induce myofibroblast differentiation.
- Re-seeding differentiated myofibroblasts onto cryopreserved amniotic membrane stromal surfaces.
- Treating differentiated myofibroblasts with amniotic membrane stromal extract.
Main Results:
- AMSCs differentiated into myofibroblasts within two passages when cultured on plastic.
- Differentiated myofibroblasts reversed to a fibroblast phenotype upon re-seeding onto amniotic membrane stroma.
- Amniotic membrane stromal extract promoted fibroblast phenotype maintenance and myofibroblast reversal without affecting cell proliferation.
Conclusions:
- The amniotic membrane stroma contains soluble factors capable of regulating mesenchymal cell differentiation.
- These findings suggest a potential new strategy for scar reversal by manipulating myofibroblast phenotype.
- Further research into these factors could lead to novel therapeutic approaches for fibrotic conditions.
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