Labeling of mesenchymal stromal cells with iron oxide-poly(L-lactide) nanoparticles for magnetic resonance imaging: uptake, persistence, effects on cellular function and magnetic resonance imaging properties

用氧化铁-聚(L-丙交酯)纳米粒子标记间充质基质细胞用于磁共振成像:摄取、持久性、对细胞功能和磁共振成像特性的影响

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作者:Gerlinde Schmidtke-Schrezenmeier, Markus Urban, Anna Musyanovych, Volker Mailänder, Markus Rojewski, Natalie Fekete, Cedric Menard, Erika Deak, Karin Tarte, Volker Rasche, Katharina Landfester, Hubert Schrezenmeier

Aims

Mesenchymal stromal cells (MSC) are the focus of research in regenerative medicine aiming at the regulatory approval of these cells for specific indications. To cope with the regulatory requirements for somatic cell therapy, novel approaches that do not interfere with the natural behavior of the cells are necessary. In this context in vivo magnetic resonance imaging (MRI) of labeled MSC could be an appropriate tool. Cell labeling for MRI with a variety of different iron oxide preparations is frequently published. However, most publications lack a comprehensive assessment of the non-interference of the contrast agent with the functionality of the labeled MSC, which is a prerequisite for the validity of cell-tracking via MRI.

Conclusions

These particles qualify for studying MSC homing and trafficking via MRI.

Methods

We studied the effects of iron oxide-poly(l-lactide) nanoparticles in MSC with flow cytometry, transmission electron microscopy (TEM), confocal laser scanning microscopy (CLSM), Prussian blue staining, CyQuant® proliferation testing, colony-forming unit-fibroblast (CFU-F) assays, flow chamber adhesion testing, immunologic tests and differentiation tests. Furthermore iron-labeled MSC were studied by MRI in agarose phantoms and Wistar rats.

Results

It could be demonstrated that MSC show rapid uptake of nanoparticles and long-lasting intracellular persistence in the endosomal compartment. Labeling of the MSC with these particles has no influence on viability, differentiation, clonogenicity, proliferation, adhesion, phenotype and immunosuppressive properties. They show excellent MRI properties in agarose phantoms and after subcutaneous implantation in rats over several weeks. Conclusions: These particles qualify for studying MSC homing and trafficking via MRI.

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