Extracellular vesicles enriched with mitochondrial components from intermittently cold-exposed adipose tissue drive metabolically active adipose regeneration via miR-296-3p

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)

Current acellular adipose tissue engineering focuses primarily on structural regeneration, whereas functional metabolic recovery remains a major challenge. Extracellular vesicles (EV) derived from adipose tissue (AT-EV) have recently emerged as potent mediators of tissue regeneration, and cold stimulation has been reported to enhance the metabolic reprogramming of AT-EV. We have previously reported that fat grafts from cold-stimulated mice exhibited enhanced survival and adipose regeneration. Yet whether cold-induced AT-EV contribute to in vivo metabolic adipose regeneration remains unclear. Moreover, the cold stimulation temperatures used in traditional mouse models are often intolerable for humans. To address this, we developed a short-term intermittent mild cold exposure (STIMCE) protocol to metabolically activate murine adipose tissue for EV isolation (STIMCE-EV). Following only 3 or 7 days of STIMCE treatment, adipose tissue exhibited increased EV secretion and enrichment of mitochondrial components. Moreover, STIMCE-EV were efficiently incorporated into human acellular adipose matrix (AAM) hydrogel and exhibited controlled release in vitro. Injectable AAM@STIMCE-EV hydrogel transplantation in nude mice showed improved adipogenesis and volume retention in situ after 2 months. Importantly, the AAM@STIMCE-EV grafts improved cold adaptation and enhanced the thermogenic functi

Evidence level

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

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