Tunneling nanotube-mediated stem cell immunomodulation dysfunction promotes adipose inflammation and insulin resistance in GDM.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Adipose-derived stem cells (ADSCs) represent a promising therapeutic resource, yet their immunometabolic regulation remains poorly defined. Here, we reveal a tunneling nanotube (TNT)-mediated communication mechanism between ADSCs and adipose tissue macrophages (ATMs) that maintains metabolic homeostasis during pregnancy. Using gestational diabetes mellitus (GDM) mouse models combined with live-cell imaging, scanning electron microscope, and multi-omics approaches, we demonstrate that mitochondrial transfer from ADSCs to ATMs via TNTs sustains ATM metabolic fitness. This process is governed by the WNT5A-RhoA-ROCK1 axis and becomes impaired under metabolic stress, driving ATMs inflammatory polarization and insulin resistance. Importantly, in situ ADSC administration restores mitochondrial transfer and improves metabolic parameters in GDM mice. Collectively, our work establishes TNT-mediated organelle sharing as a fundamental mechanism of stem cell-immune interaction and demonstrates that ADSC-based therapy represents a promising strategy for GDM by reprogramming the metabolism of immune cells.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.