In Vivo Tracking of Superparamagnetic Iron Oxide Nanoparticle Labeled Chondrocytes in Large Animal Model

Abstract

Chondrocytes have been widely used as tissue engineered seed cells for repair of focal cartilage lesions in clinic. However, in vivo behaviors of delivered chondrocytes are still poorly understood. In this study, the feasibility of in vivo tracking of superparamagnetic iron oxide nanoparticle (SPIO)-labeled chondrocytes by magnetic resonance imaging (MRI) for articular cartilage repair in minipig model was investigated. Results showed that chondrocytes were efficiently labeled by SPIO at optimal low dosages while maintaining essential cell properties. MRI SET2WI sequence revealed that marked hypointense signal void areas representing the transplanted labeled chondrocytes could be observed for at least 12 weeks. Histochemical staining confirmed the presence of Prussian blue-positive cells and GFP-positive cells at the hypointense signal void areas. These findings provide knowledge on the in vivo tracking of SPIO labeled chondrocytes on cartilage repair following transplantation in minipigs.

Dose-Response of Superparamagnetic Iron Oxide Labeling on Mesenchymal Stem Cells Chondrogenic Differentiation: A Multi-Scale In Vitro Study

“…Furthermore, SPIO labeling diminishes T2 values at 7T in a dose-dependent manner, but more strongly at 3T, where there is saturation from the lowest SPIO concentration tested. Such a dose-dependent response has already been reported at 3T in labeled porcine chondrocytes [38]. Interestingly, our results concerning the reduction of T2 relaxation time at D28, as previously observed for MSCs [39] or chondrocytes [37], are encouraging in the perspective of a post-operative follow-up in demonstrating that SPIO remain intra-cellular during this period, as demonstrated histologically.…”

“…As observed on day 28 in collagen sponges, there is a dose-dependant intracellular intracytoplasmic distribution of the fixed initial iron to the progeny of the proliferating cells without release to the surrounding media. With this in mind since on T2 weighted sequences normal cartilage appears as grey, a chondrogenic labeled implant will be easily detectible as a dark spot in the repair area in vivo , as previously observed subcutaneously [14] or intra-articularly in mice [40], rabbit [4] or pig knees [15], [38]. Most of these in vivo studies were performed by using a range of SPIO concentrations of 10 to 50 µg/ml with a MR follow-up varying from 1 to 12 weeks.…”

Controlled release of anti-inflammatory peptides from reducible thermosensitive nanoparticles suppresses cartilage inflammation

“…In studies presented here, as expected based on chondrocyte uptake of other nanoparticle carriers (chitosan (20), iron oxide (21, 22), and PLGA (23)) ranging from 50 nm to 300 nm, we observed nanoparticle uptake into endolysosomal compartments within chondrocytes (Figures 1 & 2). Further we observed reduced chondrocyte expression of inflammatory cytokines upon uptake of KAFAK-loaded nanoparticles.…”

Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair

“…Proposed cell tracking methods include PKH26 [26], iron oxide nanoparticles [27], DiI and transfection using green fluorescence protein (GFP) [28]. Nakamura et al (2012) used GFP emission to ascertain that injected cells stayed in place following insertion, their DiI labeled cells remained in the defect at 7 days but were not seen at 1 or 3 months [28].…”