Abstract 490: Enhanced Therapeutic Effects of MSC-derived Exosomes with an Injectable Hydrogel for Hindlimb Ischemia Treatment

Abstract

Mesenchymal stem cell (MSC)-derived exosomes have been recognized as new candidates for cell-free treatment of various diseases. However, maintaining the retention and stability of exosomes over time in vivo after transplantation is a major challenge in clinical application of MSC-derived exosomes. Here, we investigated if human placenta-derived MSCs (hP-MSCs) derived exosomes incorporated with chitosan hydrogel could boost the retention and stability of exosomes and further enhance their therapeutic effect. Our results demonstrated that chitosan hydrogel notably increased the stability of proteins and microRNAs in exosomes, as well as augmented the retention of exosomes in vivo as confirmed by Gaussia luciferase imaging. In addition, we evaluated the therapeutic function of hP-MSCs derived exosomes incorporated with chitosan hydrogel in a murine model of hindlimb ischemia. Our data demonstrated that chitosan hydrogel could enhance the retention of exosomes and further augment the therapeutic effects for hindlimb ischemia as revealed by firefly luciferase imaging of angiogenesis. The strategy used in this study may facilitate the development of easy and effective approaches for assessing and enhancing the therapeutic effects of stem cell-derived exosomes.

Engineered Extracellular Vesicles: Tailored-Made Nanomaterials for Medical Applications

“…Numerous studies have delivered EVs within biomaterials for the regeneration of various tissues, highlighted in Table 4. Zhang et al investigated delivering human placental MSC-derived EVs embedded within a chitosan hydrogel for muscle regeneration [134], which was found to increase retention at the defect compared to EVs injection in solution (Figure 8A). Sustained release at the defect site was observed up to 28 days, with improved functionality evidenced by increased capillary formation and tissue regeneration.…”

“…They demonstrated that the EV-functionalised hydrogel promoted chondrocyte proliferation in vitro and substantially enhanced articular cartilage repair in a rabbit defect model when compared to EVs delivered in solution (Figure 8B). [134], with permission from American Chemical Society, 2018. (B) Superior reparation of articular full-thickness rabbit defects treated with in situ forming EV-functionalised hydrogel (EHG) when compared to hydrogel alone (HG), pre-formed EV-hydrogel (Pre-EHG), EV delivery alone (Inj-Exos).…”

“…However, the majority of studies elucidating EVs composition and hence their mechanism of action, isolate these nanoparticles from 2D TCP, a highly artificial system compared to the cells' native microenvironment [139]. For example, Thippabhotla et al demonstrated that EVs derived from cervical cancer cells cultured on TCP displayed a significantly altered RNA and DNA content when compared to that of EVs derived from Adapted from [134], with permission from American Chemical Society, 2018. *, p < 0.05 compared to PBS; #, p < 0.05 compared to Exo.…”

“…EVs encapsulated within chitosan hydrogel demonstrated enhanced retention at the site of injury when compared to local delivery with EVs alone. Adapted from[134], with permission from American Chemical Society, 2018. (B) Superior reparation of articular full-thickness rabbit defects treated with in situ forming EV-functionalised hydrogel (EHG) when compared to hydrogel alone (HG), pre-formed EV-hydrogel (Pre-EHG), EV delivery alone (Inj-Exos).…”

“…(A) MSC-derived exosomes with an injectable hydrogel for hindlimb ischemia treatment. EVs encapsulated within chitosan hydrogel demonstrated enhanced retention at the site of injury when compared to local delivery with EVs alone.Adapted from[134], with permission from American Chemical Society, 2018. *, p < 0.05 compared to PBS; #, p < 0.05 compared to Exo.…”