Exosomes From Human Urine-Derived Stem Cells Encapsulated Into PLGA Nanoparticles for Therapy in Mice With Particulate Polyethylene-Induced Osteolysis.

Hui Li,Jie Xie,Yihe Hu,Xiaolei Fan,Junxiao Yang,Yinan Wang,Min Zeng

doi:10.3389/fmed.2021.781449

Abstract

Background: Periprosthetic osteolysis is the primary reason for arthroplasty failure after total joint replacement because of the generation of wear particles and subsequent bone erosion around the prosthesis, which leads to aseptic loosening. Periprosthetic osteolysis is often treated with revision surgery because of the lack of effective therapeutic agents. As key messengers of intercellular interactions, exosomes can be independently used as therapeutic agents to promote tissue repair and regeneration. In this study, we fabricated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that carry exosomes derived from human urine stem cells (USC-Exos) and explored their effects on polyethylene-induced osteolysis.Methods: USCs were identified by multipotent differentiation and flow cytometry analyses. USC-Exos were isolated and identified by transmission electron microscopy (TEM), dynamic light scattering (DLS), and western blotting. PLGA microspheres containing USC-Exos were fabricated to synthesize NPs using the mechanical double-emulsion method. The obtained NPs were characterized in terms of stability, toxicity, exosome release, and cell uptake. Then, these NPs were implanted into the murine air pouch model, and their effects on polyethylene-induced osteolysis were evaluated by microcomputed tomography (micro-CT) and histological analyses.Results: The average NP diameter was ~282 ± 0.4 nm, and the zeta potential was −2.02 ± 0.03 mV. After long-term storage at room temperature and 4°C, the NP solution was stable without significant coaggregation. In vitro release profiles indicated sustained release of exosomes for 12 days. In vivo, injection of NPs into the murine air pouch caused less osteolysis than that of USC-Exos, and NPs significantly reduced bone absorption, as indicated by histology and micro-CT scanning.Conclusion: Our findings suggest that USC-Exo-based PLGA NPs can prevent particulate polyethylene-induced osteolysis and bone loss.

Highlights

Total joint replacement can effectively treat joint diseases such as osteoarthritis, complex fractures, and osteonecrosis [1, 2]
Periprosthetic osteolysis is the primary reason for arthroplasty failure after total joint replacement because of the generation of wear particles and subsequent bone erosion around the prosthesis, which leads to aseptic loosening
Our findings suggest that USC-Exo-based poly(lactic-co-glycolic acid) (PLGA) NPs can prevent particulate polyethylene-induced osteolysis and bone loss

Summary

Introduction

Total joint replacement can effectively treat joint diseases such as osteoarthritis, complex fractures, and osteonecrosis [1, 2]. The main reason for arthroplasty failure after total joint replacement is aseptic loosening, representing ∼75% of all cases and severely impacting patients and the healthcare system [5]. No effective agents or drugs to inhibit or treat periprosthetic osteolysis have been approved, and aseptic loosening can be treated only by revision surgery. Alternative therapeutic strategies for aseptic loosening are required to ameliorate bone loss and promote bone regeneration. Periprosthetic osteolysis is the primary reason for arthroplasty failure after total joint replacement because of the generation of wear particles and subsequent bone erosion around the prosthesis, which leads to aseptic loosening. Periprosthetic osteolysis is often treated with revision surgery because of the lack of effective therapeutic agents. We fabricated poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) that carry exosomes derived from human urine stem cells (USC-Exos) and explored their effects on polyethylene-induced osteolysis

Methods

Results

Conclusion