Microneedle based adipose derived stem cells‐derived extracellular vesicles therapy ameliorates UV‐induced photoaging in SKH‐1 mice

Abstract

Extracellular vesicles from adipose derived stem cells (ADSCs‐EVs) have shown immunomodulation and anti‐photoaging effects; however, the skin barrier prevents their absorption via skin. Meanwhile, microneedle (MN) is a widely used and minimally invasive tool for dermal delivery of drugs, it also has neocollagenesis effect by creating tiny injuries and initiating wound healing process. To investigate the effect of MN combined with ADSCs‐EVs on skin aging, photoaging in SKH‐1 mice was induced by chronic exposure to ultraviolet radiation. Then the mice were treated following a split‐dorsal scheme, in which one side had MN alone or MN + EVs treatment and the other side was left untreated. For the side treated with MN alone or MN + EVs, the epidermal thickness was decreased and the skin barrier function was enhanced compared with the untreated side. However, MN + EVs group showed the least wrinkles, the highest collagen density and the most organized collagen fibers among the three groups. The level of CD11b + cell infiltration was lower in MN + EVs group than that in the MN group at 3 day after the treatment. These results indicated that MN treatment alone could improve epidermal structure and function of photoaging skin, and a combination with ADSCs‐EVs would accelerate the restoration of inflammation caused by MN and improve the content of collagen. In all, this study indicated that a combination of MN and topical applied ADSCs‐EVs was a feasible and safe strategy to ameliorate photoaging, providing a new avenue for safe administration of EVs.

The therapeutic and commercial landscape of stem cell vesicles in regenerative dermatology

“…A study by Cao et al (2021) demonstrated that the addition of EVs could enhance collagen density and organisation when compared to microneedling alone. However, the study lacked EV only controls, so the added benefit of microneedling could not be determined [17]. An alternative approach could be via the local injection of EVs.…”

“…Additionally, EVs can act as carriers for a wide range of chemical and biological drugs, enhancing cellular targeting and uptake. While the combined delivery of EVs with adjunct therapies such as microneedling or through association with biocompatible scaffolds offers the opportunity to further enhance delivery across the skin barrier and modulate their release kinetics to enhance clinical outcomes [17]. To date, the majority of published outcomes have been observed through the delivery of mesenchymal stem cell-derived EVs (MSC-EVs), with this cell source offering benefits in the translation of EV therapies due to their immunoregulatory effects and ability to be sourced allogeneically.…”

Extracellular Vesicles in Facial Aesthetics: A Review

“…It allows drugs to directly reach the dermal tissue by creating plenty of microholes to bypass the stratum corneum barrier [ 88 ]. Cao et al found that a combination of microneedle and ADSC-EVs exhibited promising anti-aging effects in photoaging skin in vivo, as indicated by the least wrinkles, the maximum collagen density, and the most organized collagen fibers compared to the other groups [ 89 ]. There is also a decrease in epidermal thickness and improved skin barrier function with higher stratum corneum hydration values and lower trans-epidermal water loss (TEWL).…”

Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases

“…Because of the existence of the skin barrier, simply applying EVs to the skin surface will sharply reduce its effectiveness. Studies have shown that ADSC-EVs combined with a microneedle roller can effectively reduce the aging phenotype of SKH-1 mice [ 167 ], but this method of promoting EV absorption could easily increase skin sensitivity. And in recent years, the microneedle patch has become a research hotspot in the field of dermatology based on its advantages of minimal invasiveness, painlessness, and high drug loading.…”