Bone marrow mesenchymal stem cells promote uterine healing by activating the PI3K/AKT pathway and modulating inflammation in rat models

BACKGROUND

Uterine injury can cause uterine scarring, leading to a series of complications that threaten women’s health. Uterine healing is a complex process, and there are currently no effective treatments. Although our previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) promote uterine damage repair, the underlying mechanisms remain unclear. However, exploring the specific regulatory roles of BMSCs in uterine injury treatment is crucial for further understanding their functions and enhancing therapeutic efficacy.

AIM

To investigate the underlying mechanism by which BMSCs promote the process of uterine healing.

METHODS

In in vivo experiments, we established a model of full-thickness uterine injury and injected BMSCs into the uterine wound. Transcriptome sequencing was performed to determine the enrichment of differentially expressed genes at the wound site. In in vitro experiments, we isolated rat uterine smooth muscle cells (USMCs) and cocultured them with BMSCs to observe the interaction between BMSCs and USMCs in the microenvironment.

RESULTS

We found that the differentially expressed genes were mainly related to cell growth, tissue repair, and angiogenesis, while the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway was highly enriched. Quantitative reverse-transcription polymerase chain reaction was used to validate differentially expressed genes, and the results demonstrated that BMSCs can upregulate genes related to regeneration and downregulate genes related to inflammation. Coculturing BMSCs promoted the migration and proliferation of USMCs, and the USMC microenvironment promoted the myogenic differentiation of BMSCs. Finally, we validated the PI3K/AKT pathway in tissues and cells and showed that BMSCs activate the PI3K/AKT pathway to promote the regeneration of uterine smooth muscle both in vivo and in vitro.

CONCLUSION

BMSCs upregulated uterine wound regeneration and anti-inflammatory factors and enhanced uterine smooth muscle proliferation through the PI3K/AKT pathway both in vivo and in vitro.

Key Words: Uterine injury; Bone marrow mesenchymal stem cells; Uterine smooth muscle cells; Phosphoinositide 3-kinase/protein kinase B pathway; Cell-cell interactions; Cell proliferation; Immune regulation; Wound regeneration

Core Tip: We identified differentially genes in uterine wound tissues through transcriptome sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that regeneration and anti-inflammatory factors were upregulated in bone mesenchymal stem cell (BMSCs) groups and that the phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin pathway was highly enriched. This study also demonstrated that BMSCs significantly promoted the proliferation and migration of uterine smooth muscle cells (USMCs) and that USMCs enhanced the myogenic differentiation of BMSCs. In vivo and in vitro experiments demonstrate that BMSCs activate the phosphoinositide 3-kinase/protein kinase B pathway in wound tissues and USMCs.

• Citation: Yang J, Yuan J, Wen YQ, Wu L, Liao JJ, Qi HB. Bone marrow mesenchymal stem cells promote uterine healing by activating the PI3K/AKT pathway and modulating inflammation in rat models. World J Stem Cells 2025; 17(1): 98349
• URL: https://www.wjgnet.com/1948-0210/full/v17/i1/98349.htm
• DOI: https://dx.doi.org/10.4252/wjsc.v17.i1.98349