Stem Cell Imaging: From Bench to Bedside

Nguyen, Patricia K.; Riegler, Johannes; Wu, Joseph C.

doi:10.1016/j.stem.2014.03.009

Cited by 215 publications

(249 citation statements)

References 111 publications

(161 reference statements)

Supporting

Mentioning

248

Contrasting

Order By: Relevance

“…One is to transfect the cells with a reporter gene 2,7 and follow-up on their proliferation through optical imaging, positron emission tomography or magnetic resonance imaging [8][9][10] . This strategy, however, requires a rather time-consuming transfection procedure that may lead to undesired phenotypical alterations and abnormalities in the transplanted cells in comparison to the native cells [11][12][13] . The second strategy is to label the cells with exogenous contrast agents, being either organic probes or inorganic nanoparticles (NPs) 14,15 .…”

Section: Introductionmentioning

confidence: 99%

Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging

et al. 2016

View full text Add to dashboard Cite

Long-term in vivo imaging of cells is crucial for the understanding of cellular fate in biological processes in cancer research, immunology or in cell-based therapies such as beta cell transplantation in type I diabetes or stem cell therapy. Traditionally, cell labelling with the desired contrast agent occurs ex vivo via spontaneous endocytosis, which is a variable and slow process that requires optimization for each particular label-cell type combination. Following endocytic uptake, the contrast agents mostly remain entrapped in the endolysosomal compartment, which leads to signal instability, cytotoxicity and asymmetric inheritance of the labels upon cell division. Here, we demonstrate that these disadvantages can be circumvented by delivering contrast agents directly into the cytoplasm via vapour nanobubble photoporation. Compared to classic endocytic uptake, photoporation resulted in 50 and 3 times higher loading of fluorescent dextrans and quantum dots, respectively, with improved signal stability and reduced cytotoxicity. Most interestingly, cytosolic delivery by photoporation prevented asymmetric inheritance of labels by daughter cells over subsequent cell generations. Instead, unequal inheritance of endocytosed labels resulted in a dramatic increase in polydispersity of the amount of labels per cell with each cell division, hindering accurate quantification of cell numbers in vivo over time. The combined benefits of cell labelling by photoporation resulted in a marked improvement in long-term cell visibility in vivo where an insulin producing cell line (INS-1E cell line) labelled with fluorescent dextrans could be tracked for up to two months in Swiss Nude mice compared to two weeks for cells labelled by endocytosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Cytosolic Delivery of Nanolabels Prevents Their Asymmetric Inheritance and Enables Extended Quantitative in Vivo Cell Imaging

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Recently, nanotechnologies have contributed to advances in in vivo high-resolution imaging to monitor stem cells and exosomes tracking and homing, providing useful insights in their mechanism of action. [18][19][20][21][22][23] To produce a detectable change in signal intensity, cells or exosomes must be labeled with magnetic resonance (MR) contrast agents. In this regard, superparamagnetic iron oxide nanoparticles, which are small crystalline magnetite structures ranging in size from 5 nm to 150 nm, have been widely used to magnetically label stem cells and exosomes.…”

mentioning

confidence: 99%

Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: a new method to obtain labeled exosomes

Busato

Bonafede

Bontempi

et al. 2016

IJN

View full text Add to dashboard Cite

Purpose Recent findings indicate that the beneficial effects of adipose stem cells (ASCs), reported in several neurodegenerative experimental models, could be due to their paracrine activity mediated by the release of exosomes. The aim of this study was the development and validation of an innovative exosome-labeling protocol that allows to visualize them with magnetic resonance imaging (MRI). Materials and methods At first, ASCs were labeled using ultrasmall superparamagnetic iron oxide nanoparticles (USPIO, 4–6 nm), and optimal parameters to label ASCs in terms of cell viability, labeling efficiency, iron content, and magnetic resonance (MR) image contrast were investigated. Exosomes were then isolated from labeled ASCs using a standard isolation protocol. The efficiency of exosome labeling was assessed by acquiring MR images in vitro and in vivo as well as by determining their iron content. Transmission electron microscopy images and histological analysis were performed to validate the results obtained. Results By using optimized experimental parameters for ASC labeling (200 µg Fe/mL of USPIO and 72 hours of incubation), it was possible to label 100% of the cells, while their viability remained comparable to unlabeled cells; the detection limit of MR images was of 10 2 and 2.5×10 3 ASCs in vitro and in vivo, respectively. Exosomes isolated from previously labeled ASCs retain nanoparticles, as demonstrated by transmission electron microscopy images. The detection limit by MRI was 3 µg and 5 µg of exosomes in vitro and in vivo, respectively. Conclusion We report a new approach for labeling of exosomes by USPIO that allows detection by MRI while preserving their morphology and physiological characteristics.

show abstract

“…Stem cell therapies provide unique opportunities for diseases of the Central Nervous System [12][13][14]. By co-transplantation of BMSCs and embryo Olfactory Ensheathing Cell (OECs) in vivo, we confirmed that spinal nervous cells conduction performance improved and the histological analysis suggested that the BMSCs differentiating into neurons cell proportion increased significantly.…”

Section: Editorialmentioning

confidence: 64%