Magnetic targeting enhances the cutaneous wound healing effects of human mesenchymal stem cell-derived iron oxide exosomes

Abstract

Human mesenchymal stem cell (MSC)-derived exosomes (Exos) are a promising therapeutic agent for cell-free regenerative medicine. However, their poor organ-targeting ability and therapeutic efficacy have been found to critically limit their clinical applications. In the present study, we fabricated iron oxide nanoparticle (NP)-labeled exosomes (Exo + NPs) from NP-treated MSCs and evaluated their therapeutic efficacy in a clinically relevant model of skin injury. We found that the Exos could be readily internalized by human umbilical vein endothelial cells (HUVECs), and could significantly promote their proliferation, migration, and angiogenesis both in vitro and in vivo. Moreover, the protein expression of proliferative markers (Cyclin D1 and Cyclin A2), growth factors (VEGFA), and migration-related chemokines (CXCL12) was significantly upregulated after Exo treatment. Unlike the Exos prepared from untreated MSCs, the Exo + NPs contained NPs that acted as a magnet-guided navigation tool. The in vivo systemic injection of Exo + NPs with magnetic guidance significantly increased the number of Exo + NPs that accumulated at the injury site. Furthermore, these accumulated Exo + NPs significantly enhanced endothelial cell proliferation, migration, and angiogenic tubule formation in vivo; moreover, they reduced scar formation and increased CK19, PCNA, and collagen expression in vivo. Collectively, these findings confirm the development of therapeutically efficacious extracellular nanovesicles and demonstrate their feasibility in cutaneous wound repair.

Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

“…Exosomes, extracellular vesicles with a diameter between 30 and 150 nm, can transport proteins and growth factors to target cells where they exert different effects [ 14 , 15 ]. Bone marrow-derived MSCs (BMSCs) possess many advantages, including easier culturing, proliferation, isolation and purification, rendering them convenient for clinical application [ 16 , 17 ].…”

3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing

“…The tube formation assay was conducted using HUVECs according to the published literature [ 30 ]. A total of 1 × 10 4 HUVECs were seeded onto Matrigel (BD, 356234) in 96-well plates and incubated in serum-free cell culture supernatant 2D-ADSCs, 3D-ADSCs and 3D/NO-ADSCs or DMEM (control) at 37°C.…”

The Role of Exosomes Derived From Mesenchymal Stromal Cells in Dermatology

“…Furthermore, Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects in vitro , which could be an important mechanism for cutaneous wound healing ( Zhang et al, 2015b ). Other proliferative markers, growth factors and migration-related chemokines such as angiotensin-2 (Ang-2) ( Liu et al, 2020 ), cyclin D1, cyclin A2 and C-X-C motif chemokine 12 (CXCL12) were significantly upregulated after hUC-MSCs-derived exosome treatments with human umbilical vein endothelial cells (HUVECs) in vitro , promoting proliferation, migration and angiogenesis ( Li X. et al, 2020 ). In this study, in vivo administration of iron oxide nanoparticle-labeled exosomes significantly increased the number of exosomes accumulated at the injury site, enhancing endothelial cell proliferation, migration and angiogenic tubule formation as well as reducing scar formation due to the increased expression of CK19, PCNA, and collagen.…”