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Collagen Type 1 Accelerates Healing of Ruptured Fetal Membranes
Haruta Mogami1, Annavarapu Hari Kishore1, R Ann Word2
1Department of Obstetrics and Gynecology, Green Center for Reproductive Biological Sciences, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Insights
Collagen type 1 gel effectively heals preterm premature rupture of membranes (pPROM) in a mouse model, improving closure rates by 90%. This extracellular matrix therapy promotes M2 macrophage infiltration and activates DDR2 signaling in amnion cells for enhanced wound healing.
Area of Science:
- Obstetrics and Gynecology
- Regenerative Medicine
- Biomaterials Science
Background:
- Preterm premature rupture of membranes (pPROM) is a significant cause of preterm birth.
- Extracellular matrix-based therapies are emerging for wound healing applications.
Purpose of the Study:
- To evaluate the efficacy of collagen type 1 gel in treating ruptured fetal membranes in a pregnant mouse model.
- To elucidate the underlying cellular and molecular mechanisms of collagen-mediated healing in pPROM.
Main Methods:
- A pregnant mouse model was utilized to induce and treat premature rupture of fetal membranes.
- Collagen type 1 gel and PBS injections were compared for their effects on membrane closure.
- Immunohistochemistry was used to analyze macrophage phenotypes (M2).
- Primary human amnion mesenchymal cells were treated with collagen type 1 gel to assess DDR2 activation and cell migration.
Main Results:
- Collagen type 1 gel injection significantly improved fetal membrane closure rates to 90% within 72 hours, compared to 40% with PBS.
- M2 macrophages, crucial for wound healing, were observed within the collagen gel matrix.
- Collagen type 1 activated discoidin domain receptor 2 (DDR2) in human amnion mesenchymal cells, leading to myosin light chain phosphorylation and enhanced cell migration.
Conclusions:
- Collagen type 1 gel demonstrates high efficacy in promoting the healing of prematurely ruptured fetal membranes.
- The therapeutic effect involves the recruitment of M2 macrophages and activation of the DDR2 signaling pathway in amnion cells.
- Matrix-directed therapeutics, specifically collagen type 1, show promise for treating pPROM and reducing preterm birth.
Abstract:
Preterm premature rupture of membranes (pPROM) is a major cause of preterm birth. Recently, extracellular matrix-directed treatment is applied for wound healing. Here, we used a pregnant mouse model to test the efficacy of collagen type 1 gel for healing of the prematurely ruptured fetal membranes. Although injection of PBS into the ruptured fetal membranes resulted in 40% closure, injection of collagen type 1 improved closure rates to 90% within 72 h. Macrophages of the M2 wound healing phenotype were entrapped in the collagen layer. In primary human amnion mesenchymal cells, collagen type 1 gels activated collagen receptor discoidin domain receptor 2 (DDR2) to induce myosin light chain phosphorylation and migration of injured amnion mesenchymal cells. These findings define the mechanisms for matrix-directed therapeutics for pPROM.
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