Abstract
BackgroundDirect intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair. However, the repair process was hindered by the absence of scaffold and poor cell–matrix interactions.MethodsIn this study, we developed a pericellular collagen I coating (PCC) on MSCs. The overall performances of MSC-PCC homing, chondrogenic differentiation, and cartilage regeneration have been comprehensively evaluated in a New Zealand rabbit model. Firstly, we examined the morphology and physical characteristics of PCC. Secondly, MSC ex-vivo cartilage slice adhesion and in-vivo cartilage defect homing were observed using multiscale methods. Thirdly, the precartilage condensation of cell pellets formed by aggregation of MSCs was examined to evaluate the cartilage-inducing potential of PCC. Finally, the cartilage regeneration by DIAI of PCC-coated MSCs was observed and scored macroscopically and histologically.ResultsIn general, the cell adhesion and homing assay revealed that PCC facilitated MSC adhesion on cartilage slices, enhancing MSC homing and retention to cartilage defect. This increased homing ratio was accompanied by an increasing cell–cell contact. Compared with naked MSCs, the cell pellets formed by PCC-coated MSCs exhibited more evident appearance of condensation. In pellets, cell–cell interaction has been significantly stimulated, inducing the expression of condensation marker N-cadherin, and subsequent chondrogenic marker collagen II and aggrecan. By 12 weeks after DIAI, cartilage defects have been repaired by MSCs to varying degrees. Overall, PCC significantly enhances the quality of cartilage regeneration judging from macroscopic observation, ICRS score, histological examination, and collagen type I, II, and X immunohistochemical staining.ConclusionsThe capacity and viability of MSCs can be enhanced by collagen I coating, which provides cues for enhancing cell homing and differentiation. Our method provides a novel strategy for stem cell therapy.
Highlights
Direct intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair
There are many promising methods applying engineered MSCs to cartilage regeneration, yet optimization of the proliferation and chondrogenic differentiation of these MSCs are poorly developed. This has led to the utilization of alternative strategies such as direct intra-articular injection (DIAI) of MSCs
Immunofluorescence staining, ultrastructure, and physical characteristic of pericellular collagen I coating (PCC) on MSCs After 2 h of coincubation, cells coated with PCC were visualized by immunofluorescence using Fluorescein isothiocyanate (FITC)-labeled antibody under the laser scanning confocal microscope (LSCM)
Summary
Direct intra-articular injection (DIAI) of mesenchymal stem cells (MSCs) is a promising technique for cartilage repair. There are many promising methods applying engineered MSCs to cartilage regeneration, yet optimization of the proliferation and chondrogenic differentiation of these MSCs are poorly developed This has led to the utilization of alternative strategies such as direct intra-articular injection (DIAI) of MSCs. It has been reported that MSCs home to target lesion sites [2]. It has been reported that MSCs home to target lesion sites [2] Based on this property, these cells may be transplanted into a cartilage defect by a simple and mini-invasive approach. These cells may be transplanted into a cartilage defect by a simple and mini-invasive approach Both animal and clinical studies have confirmed the effectiveness of DIAI in cartilage repair [3, 4]. Several efforts have been made to overcome these limitations, no satisfactory results have yet been achieved [6, 8,9,10,11,12]
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