Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model
| Autor: | Ola Mostafa, Ahmed Samy Saad, Ayman Samir Farid, Khalid Abdelaziz Ibrahim, Dina Sabry, Abeer Mostafa, Rania Ebrahim El Dosoky, Nesrine Ebrahim, Inas A. Ahmed |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
TGF-β medicine.drug_class RUNX2 UCMSCs-EVs Medicine (miscellaneous) Inflammation Tissue Adhesions Biochemistry Genetics and Molecular Biology (miscellaneous) Proinflammatory cytokine lcsh:Biochemistry 03 medical and health sciences chemistry.chemical_compound Extracellular Vesicles Fibrosis medicine Animals Humans lcsh:QD415-436 lcsh:R5-920 IL-6 business.industry IL-1 Research Mesenchymal stem cell Mesenchymal Stem Cells Cell Biology medicine.disease Estrogen Rats Vascular endothelial growth factor Disease Models Animal 030104 developmental biology chemistry TNF-α Cancer research Molecular Medicine Tumor necrosis factor alpha Female Collagen Stem cell medicine.symptom lcsh:Medicine (General) business Intrauterine adhesions |
| Zdroj: | Stem Cell Research & Therapy Stem Cell Research & Therapy, Vol 9, Iss 1, Pp 1-15 (2018) |
| ISSN: | 1757-6512 |
| Popis: | Background Mesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs). Methods In this study, we investigated the systemic administration of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UCMSCs-EVs) as a therapeutic agent for intrauterine adhesions (IUAs) caused by endometrial injury. Additionally, we investigated the therapeutic impact of both UCMSCs-EVs and estrogen either separately or in combination in a rat model. The inflammation, vascularization, proliferation, and extent of fibrosis were assessed by a histopathological and immunohistochemical assessment using transforming growth factor (TGF)-β as a fibrotic marker and vascular endothelial growth factor (VEGF) as a vascular marker. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 (inflammatory cytokines), CD140b (a marker of endometrial stem cells), and RUNX2 (an antifibrotic factor). Finally, Western blotting was used to evaluate collagen I and β-actin expression. Results The therapeutic groups treated with either UCMSCs-EVs alone or combined with estrogen exhibited a significant decrease in inflammation and fibrosis (TNF-α, TGF-β, IL-1, IL-6, RUNX2, and collagen-I) as well as a significant decrease in vascularization (VEGF) compared with the untreated rats with IUAs. The most significant results were obtained in animals with IUAs that received a combined therapy of UCMSCs-EVs and estrogen. Conclusions We conclude that the synergistic action of human UCMSCs-EVs combined with estrogen provides a highly effective alternative regenerative agent in IUA treatment. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink