Uterine Repair Mechanisms Are Potentiated by Mesenchymal Stem Cells and Decellularized Tissue Grafts Through Elevated Vegf, Cd44, and Itgb1 Gene Expression

Autores de IIS La Fe

• Lucia De Miguel Gómez

  Autor

• Sara Lopez Martinez

  Autor

• Irene Cervelló Alcaraz

  Autor

Participantes ajenos a IIS La Fe

• Bandstein, Sara
• Sehic, Edina
• Thoren, Emy
• Akouri, Randa
• Oltean, Mihai
• Brannstrom, Mats
• Hellstrom, Mats

Grupos

• Biología Reproductiva y Bioingeniería en Reproducción Humana

  

  Leader

  Nicolás Garrido Puchalt

Abstract

Transplantation of decellularized uterus tissue showed promise in supporting regeneration following uterine injury in animal models, suggesting an alternative to complete uterus transplantation for uterine factor infertility treatment. However, most animal studies utilized small grafts, limiting their clinical relevance. Hence, we used larger grafts (20 x 10 mm), equivalent to nearly one uterine horn in rats, to better evaluate the bioengineering challenges associated with structural support, revascularization, and tissue regeneration. We analyzed histopathology, employed immunohistochemistry, and investigated gene expression discrepancies in growth-related proteins over four months post-transplantation in acellular grafts and those recellularized (RC) with bone marrow-derived mesenchymal stem cells (bmMSCs). RC grafts exhibited less inflammation and faster epithelialization and migration of endogenous cells into the graft compared with acellular grafts. Despite the lack of a significant difference in the density of CD31 positive blood vessels between groups, the RC group demonstrated a better organized myometrial layer and an overall faster regenerative progress. Elevated gene expression for Vegf, Cd44, and Itgb1 correlated with the enhanced tissue regeneration in this group. Elevated Tgfb expression was noted in both groups, potentially contributing to the rapid revascularization. Our findings suggest that large uterine injuries can be regenerated using decellularized tissue, with bmMSCs enhancing the endogenous repair mechanisms.

Keywords

• uterus factor infertility; bioengineering; decellularized scaffolds; mesenchymal stem cells; infertility; uterus transplantation