Targeted mesenchymal stem cell therapy equipped with a cell-tissue nanomatchmaker attenuates osteoarthritis progression

Nahid Nasiri,Samaneh Hosseini,Fakhreddin Reihani-Sabet,Mohamadreza Baghaban Eslaminejad

doi:10.1038/s41598-022-07969-9

Nahid Nasiri, Samaneh Hosseini + Show 2 more

Open Access

https://doi.org/10.1038/s41598-022-07969-9

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Abstract

Mesenchymal stem cells (MSCs) are at the forefront of research for a wide range of diseases, including osteoarthritis (OA). Despite having attracted the attention of orthopedists, current MSC therapy techniques are limited by poor MSC implantation in tissue defects and lack of lateral tissue integration, which has restricted the efficacy of cell therapy to alleviate OA symptoms only. Here, we developed targeted MSC therapy for OA cartilage using a cell-tissue matchmaking nanoconstruct (C-TMN). C-TMN, as an MSC vehicle, consists of a central iron oxide nanoparticle armed with two types of antibodies, one directed at the MSC surface and the other against articular cartilage. We treated rat OA articular cartilage with intra-articular injections of C-TMN with and without exogenous MSCs. We observed substantial improvements in both symptomatic and radiographic OA caused by C-TMN, which was independent of exogenous MSCs. This new approach could predict a promising future for OA management.

Highlights

Mesenchymal stem cells (MSCs) are at the forefront of research for a wide range of diseases, including osteoarthritis (OA)
The immunofluorescence assay (Fig. 1b) and Prussian blue iron staining (Fig. 1c) results showed that cell-tissue matchmaking nanoconstruct (C-TMN) could more efficiently bind to MSCs than unconjugated iron oxide nanoparticles (UIN)
Prussian blue staining results revealed that MSCs endocytosed UIN but not C-TMN

Summary

Introduction

Mesenchymal stem cells (MSCs) are at the forefront of research for a wide range of diseases, including osteoarthritis (OA). Abbreviations MSCs Mesenchymal stem cells OA Osteoarthritis C-TMN Cell-tissue matchmaking nanoconstruct NP Nanoparticle AC Articular cartilage MIA Monosodium iodoacetate IA Intra-articular ACI Autologous chondrocyte implantation BM Bone marrow OAC Osteoarthritic AC Ab Antibody CTPs Cell targeting peptides COL2 Collagen type II ECM Extracellular matrix DLS Dynamic light scattering UIN Unconjugated iron oxide GAG Glycosaminoglycan PCM Pericellular matrix STR Short tandem repeat. Autologous chondrocyte implantation (ACI) and mesenchymal stem cell (MSC) therapy, as extrinsic cartilage repair factors, are two available advanced cell therapy techniques that have not been able to restore normal articular function in OA patients[2] This is mainly due to the inadequate delivery of a sufficient number of therapeutic cells, whether recruited from bone marrow (BM) and vasculature or exogenously injected, to the injured articular cartilage (AC)[3, 4]. Covalent conjugation of peptides or Abs to the surface of therapeutic cells may affect membrane protein function and disturb relevant signaling patterns, leading to abnormal ligand-receptor binding and altered cell fate[10]

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