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Dextran-coated fluorapatite crystals doped with Yb3+/Ho3+ for labeling and tracking chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo.

Abstract：

:Upconversion fluorescent nanoparticles are becoming more widely used as imaging contrast agents, owing to their high resolution and penetration depth, and avoidance of tissue auto-fluorescence and photodamage to cells. Here, we synthesized upconversion fluorescent crystals from rare-earth Yb3+ and Ho3+ co-doped fluorapatite (FA:Yb3+/Ho3+) suitable for long-term tracking and monitoring cartilage development (chondrogenesis) in bone marrow mesenchymal stem cells (BMSCs) in vitro and in vivo. We initially determined the structure, morphology and luminescence of the products using X-ray powder diffraction, transmission electron microscopy and two-photon confocal microscopy. When excited at 980 nm, FA:Yb3+/Ho3+ crystals exhibited distinct upconversion fluorescence peaks at 543 nm and 654 nm. We then conjugated FA:Yb3+/Ho3+ crystals with dextran to enhance hydrophilicity, biocompatibility and cell penetration. Next, we employed the dextran-coated FA:Yb3+/Ho3+ crystals in labeling and tracking chondrogenic differentiation processes in BMSCs stably expressing green fluorescent protein (BMSCsGFP) in vitro and in vivo. Labeled BMSCsGFP were shown to reproducibly exhibit chondrogenic differentiation potential in RT-PCR analysis, histological assessment and immunohistochemistry. We observed continuous luminescence from the FA:Yb3+/Ho3+ upconversion crystals at 4 weeks and 12 weeks post transplantation in BMSCsGFP, while GFP fluorescence in both control and crystal-treated groups significantly decreased at 12 weeks after BMSCsGFP transplantation. We therefore demonstrate the high biocompatibility and stability of FA:Yb3+/Ho3+ crystals in tracking and monitoring BMSCs chondrogenesis in vitro and in vivo, highlighting their excellent cell labeling potential in cartilage tissue engineering.

journal_name

Biomaterials

journal_title

Biomaterials

authors

Hu X,Zhu J,Li X,Zhang X,Meng Q,Yuan L,Zhang J,Fu X,Duan X,Chen H,Ao Y

doi

10.1016/j.biomaterials.2015.02.050

subject

Has Abstract

pub_date

2015-06-01 00:00:00

pages

441-51

eissn

0142-9612

issn

1878-5905

pii

S0142-9612(15)00174-X

journal_volume

pub_type

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Dextran-coated fluorapatite crystals doped with Yb3+/Ho3+ for labeling and tracking chondrogenic differentiation of bone marrow mesenchymal stem cells in vitro and in vivo.