In vivoimaging of human adipose-derived stem cells in Alzheimer’s disease animal model

Abstract

Abstract. Stem cell therapy is a promising tool for the treatment of diverse conditions, including neurodegenerative diseases such as Alzheimer's disease (AD). To understand transplanted stem cell biology, in vivo imaging is necessary. Nanomaterial has great potential for in vivo imaging and several noninvasive methods are used, such as magnetic resonance imaging, positron emission tomography, fluorescence imaging (FI) and near-infrared FI. However, each method has limitations for in vivo imaging. To overcome these limitations, multimodal nanoprobes have been developed. In the present study, we intravenously injected human adipose-derived stem cells (hASCs) that were labeled with a multimodal nanoparticle, LEO-LIVE™-Magnoxide 675 or 797 (BITERIALS, Seoul, Korea), into Tg2576 mice, an AD mouse model. After sequential in vivo tracking using Maestro Imaging System, we found fluorescence signals up to 10 days after injection. We also found strong signals in the brains extracted from hASCtransplanted Tg2576 mice up to 12 days after injection. With these results, we suggest that in vivo imaging with this multimodal nanoparticle may provide a useful tool for stem cell tracking and understanding stem cell biology in other neurodegenerative diseases. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Distribution pattern following systemic mesenchymal stem cell injection depends on the age of the recipient and neuronal health

“…MSCs first accumulate in the lung 24–48 hours after transplantation but can be found later in the liver, kidney, spleen, and other organs, particularly those showing injury [21]. Multimodal MRI nanoparticles with enhanced near-infrared fluorescence have been used recently to perform in-vivo imaging of human adipose-derived stem cells in an Alzheimer’s disease mouse model [22]. Cells administered via tail-vein injection were observed in the tail, body, and brain of Alzheimer’s disease mice up to 10 days after transplantation (with the strongest signal at day 3), but not in the brains of wild-type (WT) controls [22].…”

“…Multimodal MRI nanoparticles with enhanced near-infrared fluorescence have been used recently to perform in-vivo imaging of human adipose-derived stem cells in an Alzheimer’s disease mouse model [22]. Cells administered via tail-vein injection were observed in the tail, body, and brain of Alzheimer’s disease mice up to 10 days after transplantation (with the strongest signal at day 3), but not in the brains of wild-type (WT) controls [22]. Post-mortem examination of organs revealed weak fluorescent signals in WT brain tissue, suggesting that some cells are able to cross the blood–brain barrier (BBB) in young animals.…”

“…However, the strongest signals were observed in the Alzheimer’s disease mouse brains, which the authors attribute to leakage of the BBB brought about as a result of neurological disease. In addition, human adipose-derived stem cells had transmigrated to the gastrointestinal tract, kidney, liver, and bladder of all injected mice [22]. …”

In vivo near-infrared imaging for the tracking of systemically delivered mesenchymal stem cells: tropism for brain tumors and biodistribution

“…NIR imaging offers new opportunities as a sensitive and noninvasive detection technique for diagnostics that allows deeper penetration into tissues with minimum background interference. 18,19 The successful clinical application of MSC-based tumor therapies needs noninvasive imaging approaches for monitoring tumor progression and treatment outcomes in real time.…”

Stem Cell Treatment for Alzheimer’s Disease

“…The transplantation of ADSCs allowed them to differentiate into neuron-like and astrocyte-like cells around the hematoma, accompanied with up-regulation of vascular endothelial growth factor expression and improvement of neural function, suggesting that ADSCs benefit neural differentiation and induce functional improvement in the rat [47]. When human ADSCs were intravenously injected into an AD mouse models, these cells could be found in the brain up to 12 days after their injection [48]. One report suggested that, when transplanted into the brain, adipose-derived MSCs (AMSCs) improved Ach levels as well as cognitive and locomotor functions in aged mice, and modulated microglia activation [29,49].…”