In Vivo Photoacoustic Tracking of Mesenchymal Stem Cell Viability

Abstract

Adult stem cell therapy has demonstrated improved outcomes for treating cardiovascular diseases in preclinical trials. The development of imaging tools may increase our understanding of the mechanisms of stem cell therapy, and a variety of imaging tools have been developed to image transplanted stem cells in vivo; however, they lack the ability to interrogate stem cell function longitudinally. Here, we report the use of a nanoparticle-based contrast agent that can track stem cell viability using photoacoustic imaging. The contrast agent consists of inert gold nanorods coated with IR775c, a reactive oxygen species (ROS) sensitive near-infrared dye. Upon cell death, stem cells produce ROS to degrade the cell. Using this feature of stem cells, the viability can be measured by comparing the IR775c signal to the ROS insensitive gold nanorod signal, which can also be used to track stem cell location. The nanoprobe was successfully loaded into mesenchymal stem cells (MSCs), and then, MSCs were transplanted into the lower limb of a mouse and imaged using combined ultrasound and photoacoustic imaging. MSC viability was assessed using the nanoprobe and displayed significant cell death within 24 h and an estimated 5% viability after 10 days. This nanoparticle system allows for longitudinal tracking of MSC viability in vivo with high spatial and temporal resolution which other imaging modalities currently cannot achieve.

Gold Nanomaterials for Imaging-Guided Near-Infrared in vivo Cancer Therapy

“…They had been prepared to quantitate and image mesenchymal stem cells for living mice in real time, and the results showed the spatial resolution of 340 μm and the temporal resolution of 0.2 s (Jokerst et al, 2012b). To track the stem cell in cardiovascular diseases, silica-gold nanorods with coating IR775c, which was a sensitive dye of reactive oxygen species, had been developed for PAI (Dhada et al, 2019). The nanoprobe had a high spatial and temporal resolution, and they displayed a 5% viability of mesenchymal stem cells after 10 days.…”

Photoacoustic imaging of cells in a three-dimensional microenvironment

“…This property means that melanoma cells are traceable for monitoring cell proliferation in engineered 3D porous scaffolds [58]. Making use of cellular endocytosis processes, AuNPs can be loaded into stem cells or macrophages as a PA contrast agent, which opens the possibility of the long-term tracking and monitoring of stem cells or macrophages in a 3D fibrin or gelatin scaffold through multimodal US and PA imaging for utilization in investigations of stem cell therapy [59][60][61][62][63][64][65]. Nanoparticles are generally more likely to accumulate in a tumor lesion due to the enhanced permeability and retention of the leaky tumor blood vessels [66], which has been demonstrated by the passive targeting and accumulation of AuNPs at a tumor site [67].…”

Illuminating the Regenerative Properties of Stem Cells In Vivo with Bioluminescence Imaging

“…[12,139,140] Photoacoustic imaging, a version of ultrasound that relies on optical absorption, is also gaining popularity for in vivo imaging. [141,142] Table 2 summarizes some important attributes of each imaging modality, including sensitivity and spatial resolution.…”