<p>Comparison of the Therapeutic Effect of Allogeneic and Xenogeneic Small Extracellular Vesicles in Soft Tissue Repair</p>

Abstract

Small extracellular vesicles (sEV) are a heterogeneous group of vesicles that consist of proteins, lipids and miRNA molecules derived from the cell of origin. Although xenogeneic sEV have been applied for soft tissue regeneration successfully, the regeneration effect of allogeneic and xenogeneic sEV has not been compared systematically. Methods: Our previous study has shown that sEV derived from rat adipose tissue successfully induced neoadipose regeneration. In this study, sEV were isolated from rat adipose tissue (r-sEV-AT) and porcine adipose tissue (p-sEV-AT), the morphology, size distribution and marker proteins expression of r-sEV-AT and p-sEV-AT were characterized. Besides, the sEV/AT ratio was evaluated and compared between r-sEV-AT and p-sEV-AT. Rat adipose-derived stromal/ stem cells (rASCs) and rat aorta endothelial cells (rECs) were adopted to test the cellular response to allogeneic and xenogeneic sEV-AT. The effects of allogeneic and xenogeneic sEV-AT on host cells migration and neoadipose formation were evaluated in a subcutaneous customdesigned model. A full-thickness skin wound healing model was used to further compare the ability of allogeneic and xenogeneic sEV-AT in inducing complex soft tissue regeneration. Results: p-sEV-AT showed similar morphology and size distribution to r-sEV-AT. Marker proteins of sEV were detected in both r-sEV-AT and p-sEV-AT. The sEV/AT ratio of porcine was slightly higher than that of rat. The effects of r-sEV-AT and p-sEV-AT on the differentiation of rASCs and rECs showed no significant difference. When allogeneic and xenogeneic sEV-AT were subcutaneously implanted into the back of SD rats, the host cells chemotactic infiltration was observed in 1 week and neoadipose tissue formation was induced in 8 weeks; no significant difference was observed between allogeneic and xenogeneic sEV-AT. For complex soft tissue regeneration, both allogeneic and xenogeneic sEV-AT significantly promoted wound re-epithelialization, granulation tissue formation and hair follicle regeneration and then accelerated skin wound healing. Conclusion: Our results demonstrated that sEV derived from the same tissues of different species might be loaded with similar therapeutic substance benefitting tissue repair and regeneration, and paved the way for future research aimed at xenogeneic sEV application.

Small Extracellular Vesicles Derived from Adipose Tissue Prevent Bisphosphonate-Related Osteonecrosis of the Jaw by Promoting Angiogenesis

“…sEV were isolated from rat adipose tissue using a kit-based ultrafiltration method we have previously reported. 16 , 17 Transmission electron microscopy analysis confirmed that sEV-AT were round-shaped vesicles surrounded by a bilayer membrane ( Figure 1A ). Nanoparticle tracking analysis by ZataView confirmed the size and its distribution.…”

“… 33 Our previous study found the potential of sEV-AT on angiogenesis and soft tissue regeneration. 16 , 17 Furthermore, 45 conserved miRNAs were enriched in sEV-AT compared to sEV derived from ADSCs according to our previous study. These miRNAs were reported to participate in various functions, such as adipogenesis, angiogenesis, or metabolism.…”

“…sEV-AT were prepared as previously described. 16 , 17 Fat pads were isolated from 4-week-old SD rats. Minced fat pieces were cultured with Serum-free α-modified Eagle’s medium (α-MEM, HyClone, Utah, USA) in a Celstir spinner flask (Wheaton, USA) at 100 rpm, 37°C, in 5% CO 2 for 48 h. After removing tissue pieces by gauze and cellular debris by centrifugation (2000 g, 4°C, 20 min), the supernatant was filtered through a 40 μm filter (Corning, NY, USA) to get adipose tissue extract (ATE).…”

“…Our previous studies suggest that sEV-AT can promote proliferation, migration, and angiogenic potential of endothelial cells and contribute to soft tissue regeneration. 16 , 17 However, the therapy potential of sEV-AT requires further study.…”

Biopolímeros: Aplicaciones de andamios en medicina regenerativa

“…Mediante la implantación de este nuevo material celular sobre un tejido dañado pueden lograr su recuperación (Serrato, Nieto, & Aguilera, 2015). Las células pueden ser obtenidas ex vivo mediante un cultivo autogénico es decir de las células del mismo paciente o xenogénico si proviene de otro (Dong et al, 2020). Su principal aportación se ha visto en el trasplante de médula ósea o transfusiones sanguíneas con la finalidad de reconstruir el tejido hematopoyético y el sistema inmune; ayudando a combatir enfermedades relacionadas con osteoporosis, aumentando la densidad ósea total, calcio sérico, espacio medular y disminuyendo el riesgo de fracturas (Ejeian et al,2020).…”