Remimazolam impairs bone marrow mesenchymal stem cell function and attenuates the tumor-promoting ability

Area of Science:

• Stem Cell Biology
• Anesthesiology
• Cancer Research

Background:

• Bone marrow mesenchymal stem cells (BMMSCs) are crucial for tissue regeneration but also implicated in tumor progression.
• Anesthetics like propofol may adversely affect stem cell functions, necessitating comparison with newer agents like remimazolam.

Purpose of the Study:

• To evaluate and compare the inhibitory effects of remimazolam and propofol on BMMSC biological functions, including proliferation, migration, stemness, and tumor-promoting capacity.
• To explore the underlying molecular mechanisms and signaling pathways involved.

Main Methods:

• Cell viability (CCK-8), colony formation, adipogenic, and osteogenic differentiation assays were used to assess BMMSC functions.
• Network pharmacology analysis identified common target genes and pathways for remimazolam and propofol.
• Transwell assays, flow cytometry, and western blot analyzed the impact of conditioned media on gastric cancer cells.

Main Results:

• Remimazolam inhibited BMMSC proliferation, migration, and osteogenic differentiation, while promoting adipogenic differentiation and reducing stemness.
• Remimazolam demonstrated less pronounced inhibitory effects on these BMMSC processes compared to propofol.
• Network pharmacology indicated remimazolam modulates IL-8 via the PI3K/AKT pathway, attenuating BMMSC-driven tumor promotion.

Conclusions:

• Remimazolam exerts greater inhibitory effects on BMMSC stemness and paracrine function than propofol, significantly reducing their tumor-promoting capacity.
• Findings support remimazolam's potential for rational clinical application in anesthesia, considering its impact on stem cell behavior.