Prussian blue nanocubes as a multimodal contrast agent for image-guided stem cell therapy of the spinal cord

Kubelick, Kelsey P.; Emelianov, Stanislav

doi:10.1016/j.pacs.2020.100166

Cited by 31 publications

(34 citation statements)

References 38 publications

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“…Human adipose-derived mesenchymal stem cells (MSCs; Lonza) were labeled with PBNCs using previously reported methods, 4 and minimal impact on stem cell viability and multipotency following labeling was observed through in vitro assessments, which are commonly performed to independently assess nanoparticle impact on cellular function and anticipate effects in vivo. 25 Briefly, at roughly 80% confluence, MSCs were incubated with PBNC-containing media overnight.…”

Section: Stem Cell Labeling Protocolmentioning

confidence: 99%

“…Following beamforming and envelope detection using the built-in Vevo LAZR imaging system protocols, combined US/PA datasets were exported to MATLAB (Mathworks Inc.) for additional postprocessing using the methods developed in our previous ex vivo studies. 4 During needle insertion, PA data was segmented to primarily color the needle shaft red. During the cell injection, PA data were further segmented to distinguish PBNC-labeled MSCs, which were primarily colored blue.…”

Section: In Vivo Intraoperative Imaging With Us/pamentioning

confidence: 99%

“…Therefore, we developed an alternative imaging approach to detect stem cells in the spinal cord using a unique nanoconstruct, Prussian blue nanocubes (PBNCs). 4 PBNCs are composed of Prussian blue dye, which is clinically approved to treat heavy metal poisoning, and iron oxide nanoparticles, which are under assessment in clinical trials or already approved for certain imaging applications. 10,11 The material composition of PBNCs results in PA and MR imaging contrast.…”

Section: Introductionmentioning

confidence: 99%

“…10 Our earlier ex vivo studies in excised spinal cords validated PA/MR agreement. 4 However, in vivo translation is faced with many challenges by attempting to add US/PA to a complex, risky surgical procedure, which is further magnified by motion, background signals, increased imaging depth, and the need for fast image acquisition, among many other factors.…”

Section: Introductionmentioning

confidence: 99%

“…Previous ex vivo studies using PA imaging in the spine demonstrate the capabilities of new imaging tools to guide surgery and therapies. 3,4,13,23,24 Current in vivo findings on intraoperative US/PA guidance are vital to supporting further development of the trimodal US/PA/MR imaging approach to monitor stem cell therapies in the spinal cord. Results may extend to other research and clinical spine-related applications in intra-and postoperative settings.…”

Section: Introductionmentioning

confidence: 99%

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In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

Kubelick

Emelianov

2020

Neurophoton.

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Significance: Stem cell therapies are of interest for treating a variety of neurodegenerative diseases and injuries of the spinal cord. However, the lack of techniques for longitudinal monitoring of stem cell therapy progression is inhibiting clinical translation. Aim: The goal of this study is to demonstrate an intraoperative imaging approach to guide stem cell injection to the spinal cord in vivo. Results may ultimately support the development of an imaging tool that spans intra-or postoperative environments to guide therapy throughout treatment. Approach: Stem cells were labeled with Prussian blue nanocubes (PBNCs) to facilitate combined ultrasound and photoacoustic (US/PA) imaging to visualize stem cell injection and delivery to the spinal cord in vivo. US/PA results were confirmed by magnetic resonance imaging (MRI) and histology. Results: Real-time intraoperative US/PA image-guided injection of PBNC-labeled stem cells and three-dimensional volumetric images of injection provided feedback necessary for successful delivery of therapeutics into the spinal cord. Postoperative MRI confirmed delivery of PBNClabeled stem cells. Conclusions: The nanoparticle-augmented US/PA approach successfully detected injection and delivery of stem cells into the spinal cord, confirmed by MRI. Our work demonstrated in vivo feasibility, which is a critical step toward the development of a US/PA/MRI platform to monitor regenerative spinal cord therapies.

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Section: Stem Cell Labeling Protocolmentioning

confidence: 99%

Section: In Vivo Intraoperative Imaging With Us/pamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

Kubelick

Emelianov

2020

Neurophoton.

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Multi-scale optoacoustic molecular imaging of brain diseases

Razansky

Klohs

2021

Eur J Nucl Med Mol Imaging

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The ability to non-invasively visualize endogenous chromophores and exogenous probes and sensors across the entire rodent brain with the high spatial and temporal resolution has empowered optoacoustic imaging modalities with unprecedented capacities for interrogating the brain under physiological and diseased conditions. This has rapidly transformed optoacoustic microscopy (OAM) and multi-spectral optoacoustic tomography (MSOT) into emerging research tools to study animal models of brain diseases. In this review, we describe the principles of optoacoustic imaging and showcase recent technical advances that enable high-resolution real-time brain observations in preclinical models. In addition, advanced molecular probe designs allow for efficient visualization of pathophysiological processes playing a central role in a variety of neurodegenerative diseases, brain tumors, and stroke. We describe outstanding challenges in optoacoustic imaging methodologies and propose a future outlook.

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Iron Oxide Nanoparticles in Mesenchymal Stem Cell Detection and Therapy

Mehta

2022

Stem Cell Rev and Rep

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Mesenchymal stem cells (MSCs) exhibit regenerative and reparative properties. However, most MSC-related studies remain to be translated for regular clinical usage, partly due to challenges in pre-transplantation cell labelling and post-transplantation cell tracking. Amidst this, there are growing concerns over the toxicity of commonly used gadolinium-based contrast agents that mediate in-vivo cell detection via MRI. This urges to search for equally effective but less toxic alternatives that would facilitate and enhance MSC detection post-administration and provide therapeutic benefits in-vivo. MSCs labelled with iron oxide nanoparticles (IONPs) have shown promising results in-vitro and in-vivo. Thus, it would be useful to revisit these studies before inventing new labelling approaches. Aiming to inform regenerative medicine and augment clinical applications of IONP-labelled MSCs, this review collates and critically evaluates the utility of IONPs in enhancing MSC detection and therapeutics. It explains the rationale, principle, and advantages of labelling MSCs with IONPs, and describes IONP-induced intracellular alterations and consequent cellular manifestations. By exemplifying clinical pathologies, it examines contextual in-vitro, animal, and clinical studies that used IONP-labelled bone marrow-, umbilical cord-, adipose tissue- and dental pulp-derived MSCs. It compiles and discusses studies involving MSC-labelling of IONPs in combinations with carbohydrates (Venofer, ferumoxytol, dextran, glucosamine), non-carbohydrate polymers [poly(L-lysine), poly(lactide-co-glycolide), poly(L-lactide), polydopamine], elements (ruthenium, selenium, gold, zinc), compounds/stains (silica, polyethylene glycol, fluorophore, rhodamine B, DAPI, Prussian blue), DNA, Fibroblast growth Factor-2 and the drug doxorubicin. Furthermore, IONP-labelling of MSC exosomes is reviewed. Also, limitations of IONP-labelling are addressed and methods of tackling those challenges are suggested. Graphical Abstract

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Prussian blue nanocubes as a multimodal contrast agent for image-guided stem cell therapy of the spinal cord

Cited by 31 publications

References 38 publications

In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

In vivo photoacoustic guidance of stem cell injection and delivery for regenerative spinal cord therapies

Multi-scale optoacoustic molecular imaging of brain diseases

Iron Oxide Nanoparticles in Mesenchymal Stem Cell Detection and Therapy

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