Tracking Of Stem Cells Research Articles

Real-Time Imaging Tracking of Mesenchymal Stem Cells Labeled with Lipid-Poly(lactic-co-glycolic acid) Nanobubbles.

Stem-cell-based therapy has attracted considerable attention due to the significant benefits to patients experiencing a wide range of diseases and injuries. However, their underlying mechanism of action is not completely understood. One main reason is the lack of imaging tools for real-time tracking of deep-seated transplanted stem cells. For the present study, we exploited a lipid poly(lactic-co-glycolic acid) nanobubble (LPN) probe with nanoscale size, good compatibility, and strong contrast-enhanced ultrasound signals. Due to the nanoscale particle size, cellular labeling of mesenchymal stem cells can be achieved via incubation with LPNs. Significantly enhanced ultrasound images of these labeled stem cells were obtained in vitro and in vivo. More importantly, the labeled stem cells could be tracked by ultrasound imaging for up to 5 days. Additional evaluation found that the in vivo detection limit achieved 2,000 labeled stem cells in the subcutaneous tissues of living mice. Our study presents a strategy to achieve real-time ultrasound imaging tracking, paving the way for an investigation on the underlying mechanism and future clinical application of stem cell therapy.

NCP:Fe-A Biomineral Magnetic Nanocontrast Agent for Tracking Implanted Stem Cells in Brain Using MRI.

In vivo tracking of transplanted stem cells to monitor their migration, biodistribution, and engraftment in the host tissue is important for assessing the efficacy of stem cell therapeutics. Here, we report a biomineral nanocontrast agent, iron doped calcium phosphate nanoparticles (nCP:Fe), for the in vivo tracking of stem cells in brain using magnetic resonance imaging (MRI). We have synthesized ∼100 nm sized nCP nanoparticles doped with 9.81 wt % Fe3+. In vitro studies using mesenchymal stem cells (MSCs) showed excellent biocompatibility for nCP:Fe with ∼87% labeling efficiency under optimized conditions (100 μg/mL, 6 h). Most importantly, the labeling was not found to affect the neurogenic differentiation potential of MSCs. MRI of labeled cells (∼22.34 pg Fe/cell) showed significant reduction in T2 relaxation time from 195 to 89 ms, rendering dark contrast. In vivo transplantation of labeled cells (1 × 106 cells) in external capsule of healthy rat brain showed a clearly distinguishable hypointense (dark) region in T2 weighted MR images, which remained visible up to 30 days. Subsequently, MRI tracking of labeled MSCs transplanted intracerebrally, 3 mm near to the LPS induced inflammatory site in brain, showed successful migration of labeled MSCs toward the site of inflammation. The cell migration was confirmed ex vivo by Prussian-blue (Fe3+) and Alizarin-red (Ca2+) staining of tissue sections, where individual cells were found migrated to the site of inflammation over a period of 30 days. In summary, our results clearly show that, as a biocompatible mineral composition, nCP:Fe is a promising magnetic nanocontrast agent for MRI based cell tracking in vivo.

Comparison of different uncoated and starch-coated superparamagnetic iron oxide nanoparticles: Implications for stem cell tracking

However, labelling of stem cells using nanoparticles (NPs) for tracking purpose has been intensively investigated, the biosafety of these materials needs more clarification. Herein, different forms of iron oxide Fe2O3, Fe3O4, and CoxNi1−x Fe2O4 NPs either uncoated or starch-coated (ST-coated) were prepared. We successfully labelled adipose-derived stem cells (ASCs) using these NPs with the aid of lipofectamine as a transfection agent (TA). We then evaluated the effect of these NPs on stem cell proliferation, viability, migration and angiogenesis. Results showed that ASCs labelled with Fe2O3, Fe3O4, ST-Fe2O3 and ST-Fe3O4 did not show any significant difference in proliferation compared to that of TA-treated cells. Moreover, they have shown a protective effect against apoptosis. Conversely, CoxNi1−x Fe2O4 NPs caused a significant decrease in cell proliferation. Compared to that of the TA-treated cells, the migration capacity of cells labelled with Fe2O3, Fe3O4 and CoxNi1−xFe2O4 was significantly compromised. Interestingly, the ST-coated composites reversed this effect. Among the groups treated with different NPs, the angiogenic potential of the ASCs was most robust in the ST-Fe2O3-treated group. In conclusion, labelling ASCs with ST-Fe2O3 NPs enhanced cell migration and angiogenic potential and conferred higher resistance to apoptosis than labelling the cells with the other tested NPs.

A Safe and Effective Magnetic Labeling Protocol for MRI-Based Tracking of Human Adult Neural Stem Cells.

Magnetic resonance imaging (MRI) provides a unique tool for in vivo visualization and tracking of stem cells in the brain. This is of particular importance when assessing safety of experimental cell treatments in the preclinical or clinical setup. Yet, specific imaging requires an efficient and non-perturbing cellular magnetic labeling which precludes adverse effects of the tag, e.g., the impact of iron-oxide-nanoparticles on the critical differentiation and integration processes of the respective stem cell population investigated. In this study we investigated the effects of very small superparamagnetic iron oxide particle (VSOP) labeling on viability, stemness, and neuronal differentiation potential of primary human adult neural stem cells (haNSCs). Cytoplasmic VSOP incorporation massively reduced the transverse relaxation time T2, an important parameter determining MR contrast. Cells retained cytoplasmic label for at least a month, indicating stable incorporation, a necessity for long-term imaging. Using a clinical 3T MRI, 1 × 103 haNSCs were visualized upon injection in a gel phantom, but detection limit was much lower (5 × 104 cells) in layer phantoms and using an imaging protocol feasible in a clinical scenario. Transcriptional analysis and fluorescence immunocytochemistry did not reveal a detrimental impact of VSOP labeling on important parameters of cellular physiology with cellular viability, stemness and neuronal differentiation potential remaining unaffected. This represents a pivotal prerequisite with respect to clinical application of this method.

Dual-Modal Imaging-Guided Precise Tracking of Bioorthogonally Labeled Mesenchymal Stem Cells in Mouse Brain Stroke.

Noninvasive and precise stem cell tracking after transplantation in living subject is very important to monitor both stem cell destinations and their in vivo fate, which is closely related to their therapeutic efficacy. Herein, we developed bicyclo[6.1.0]nonyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-NPs) as a delivery system of dual-modal stem cell imaging probes. Near-infrared fluorescent (NIRF) dye Cy5.5 was chemically conjugated to the BCN-NPs, and then oleic acid-coated superparamagnetic iron oxide nanoparticles (OA-Fe3O4 NPs) were encapsulated into BCN-NPs, resulting in Cy5.5-labeled and OA-Fe3O4 NP-encapsulated BCN-NPs (BCN-dual-NPs). For bioorthogonal labeling of human adipose-derived mesenchymal stem cells (hMSCs), first, hMSCs were treated with tetra-acetylated N-azidoacetyl-d-mannosamine (Ac4ManNAz) for generating azide (-N3) groups onto their surface via metabolic glycoengineering. Second, azide groups on the cell surface were successfully chemically labeled with BCN-dual-NPs via bioorthogonal click chemistry in vitro. This bioorthogonal labeling of hMSCs could greatly increase the cell labeling efficiency, safety, and imaging sensitivity, compared to only nanoparticle-derived labeling technology. The dual-modal imaging-guided precise tracking of bioorthogonally labeled hMSCs was tested in the photothrombotic stroke mouse model via intraparenchymal injection. Finally, BCN-dual-NPs-labeled hMSCs could be effectively tracked by their migration from the implanted site to the brain stroke lesion using NIRF/T2-weighted magnetic resonance (MR) dual-modal imaging for 14 days. Our observation would provide a potential application of bioorthogonally labeled stem cell imaging in regenerative medicine by providing safety and high labeling efficiency in vitro and in vivo.

Hyperpolarized 129 Xe imaging of embryonic stem cell-derived alveolar-like macrophages in rat lungs: proof-of-concept study using superparamagnetic iron oxide nanoparticles.

To measure regional changes in hyperpolarized 129 Xe MRI signal and apparent transverse relaxation ( ) because of instillation of SPION-labeled alveolar-like macrophages (ALMs) in the lungs of rats and compare to histology. MRI was performed in 6 healthy mechanically ventilated rats before instillation, as well as 5 min and 1 h after instillation of 4 million SPION-labeled ALMs into either the left or right lung. maps were calculated from 2D multi-echo data at each time point and changes in were measured and compared to control rats receiving 4 million unlabeled ALMs. Histology of the ex vivo lungs was used to compare the regional MRI findings with the locations of the SPION-labeled ALMs. Regions of signal loss were observed immediately after instillation of unlabeled and SPION-labeled ALMs and persisted at least 1 h in the case of the SPION-labeled ALMs. This was reflected in the measurements of . One hour after the instillation of SPION-labeled ALMs, the decreased to 54.0 ± 7.0% of the baseline, compared to a full recovery to baseline after the instillation of unlabeled ALMs. Histology confirmed the co-localization of SPION-labeled ALMs with regions of signal loss and decreases for each rat. Hyperpolarized 129 Xe MRI can detect the presence of SPION-labeled ALMs in the airways 1 h after instillation. This approach is promising for targeting and tracking of stem cells for the treatment of lung disease.

54: Structural and Functional Tracking of Stem Cells on a Muscle Regeneration Model Through Noninvasive Multimodal Imaging

Introduction: During the last decade, stem cell therapy has rapidly progressed and is considered one of the most prominent therapeutic strategies for a broad range of fatal diseases. Regardless of the intense research and the continuous advances on this topic, the current therapeutic approaches are still lacking on the efficient non-invasive optimization of the treatment. To overcome these barriers, the design of tools, which could provide real-time tracking of transplanted cells, allowing the early monitoring of their biodistribution and viability, is of outmost importance. Gold nanoparticles (GNPs) are established contrast agents in Computed Tomography (CT) and they can be easily radiolabelled and imaged through Single Photon Emission Tomography (SPECT). Following these methods, non-invasive imaging can be used to perform cell tracking, in a stem cell therapy scheme regarding muscle regeneration. Methods & Materials: Biocompatible and functional nano-based multimodal imaging agents are developed in order to enable non-invasive monitoring of living stem cells in small animal models through SPECT and CT imaging (Figure 1). The in vivo platform and methodology to track stem cells fate was established based on two different GNPs samples (gold coated - magnetic core NPs manufactured by MJR PharmJet and by Bar-Ilan University). The imaging studies were performed on a SPECT and on a CT imaging system by Molecubes (γ-CUBE and x-CUBE), providing spatial resolution of 0.6 mm and 0.05 mm, respectively. Results & Discussion: The purpose of this study is to present the workflow and first results of monitoring living stem cells on a muscle regeneration mouse model, through SPECT/CT imaging. The stem cells are labelled with [111In] In DTPA and GNPs, through an established protocol and kinetics are monitored non-invasively through CT and SPECT. The number of cells remaining in the region under treatment is also quantified, giving a preliminary estimation of the success of a cell therapy scheme. Conclusion: An in vivo platform and a standardised methodology to perform stem cell tracking on a muscle regeneration model, through non-invasive SPECT/CT imaging, were established and are being presented. The first results, showing the fate of the GNPs and of labelled cells is being presented. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 761031. This study was co-supported through the Programme of Industrial Scholarships of Stavros Niarchos Foundation. Figure 1. The concept of the nTrack project: non-invasive imaging to perform cell tracking, in a stem cell therapy scheme regarding muscle regeneration. Figure 2. GNPs as a CT contrast agent, to label and track stem cells after intamascular injection on a muscle regeneration model.

Tracking of GFP-labeled unrestricted somatic stem cells transplanted in the sepsis mouse model

Cell-based therapy provides a promising approach for the treatment of sepsis and related disorders. Fate determination of transplanted cells is the most essential issue for cell therapist. Optical imaging is the reliable, time and cost-effective system for cell tracking. The present study was aimed to apply an optical imaging system for monitoring of GFP-labeled unrestricted somatic stem cells in the sepsis animal model. In vivo imaging showed the most accumulation of intravenously injected cells into the lungs and liver of septic mice. Thereafter, the imaging data were more approved by flow cytometry and immunohistochemistry staining. Cellular localization in septic lungs and liver that observed by optical imaging technique may offer beneficial evidence for designing of sepsis clinical trials.

New Opportunities: Second Harmonic Generation of Boron‐Doped Graphene Quantum Dots for Stem Cells Imaging and Ultraprecise Tracking in Wound Healing

AbstractSecond harmonic generation (SHG) has recently emerged, having the advantages of no bleaching, no blinking, and no signal saturation, as well as a high signal to‐noise ratio compared to fluorescence. Existing SHG probes are based on heavy metal or organic dye molecules, which have the shortcomings of toxicity, a large size, or photoinstability. To address the urgent need for long‐term tracking and imaging in organisms, boron‐doped graphene quantum dots (B‐GQDs), a highly biocompatible graphene based with a strong and photostable SHG signal is first synthesized and is further applied for stem cell imaging and tracking in wounds. The results demonstrate the possibility of stem cell internalization of B‐GQDs as a SHG probe and show no hindering of the stem cell's central physiological activities such as differentiation. Most importantly, B‐GQDs are successfully tracked in skin tissue in vivo after the labeled mouse mesenchymal stem cells being implanted over 35 days. This work will inspire the development of doped graphene quantum dot materials and promote the broad use of B‐GQDs in future molecular imaging, drug delivery, and stem cell therapy.

SPIO nanoparticle-labeled bone marrow mesenchymal stem cells inhibit pulmonary EndoMT induced by SiO2

Endothelial-mesenchymal transition (EndoMT) is a key step during lung fibrosis. Studies have shown that bone marrow mesenchymal stem cells (BMSCs) may act as therapeutic candidates for lung fibrosis. However, the effects of BMSCs on EndoMT induced by SiO2 have not been elucidated, and means to label and track grafted cells have been lacking. The current study explored whether BMSCs prevented pulmonary fibrosis by targeting EndoMT, as well as analyzed the distribution of BMSCs labeled with superparamagnetic iron oxide (SPIO) nanoparticles during treatment. TIE2-GFP mice, human umbilical vein endothelial cells (HUVECs), and BMSCs labeled with SPIO nanoparticles were used to explore the distributions and therapeutic effects of BMSCs in vivo and in vitro. We found that BMSCs reversed lung fibrosis by targeting EndoMT in vivo. Furthermore, we show that BMSCs labeled with SPIO nanoparticles could be used to track stem cells reliably in the lungs for 14 days. Conditioned medium from BMSCs attenuated the increased functional changes and reversed the SiO2-induced upregulation of ER stress and autophagy markers irrespective of whether they were nanoparticle labeled or not. Our findings identify novel methods to track labeled BMSCs with therapeutic potential.

Hyaluronan-Based Grafting Strategies for Liver Stem Cell Therapy and Tracking Methods.

Cell adhesion is essential for survival, it plays important roles in physiological cell functions, and it is an innovative target in regenerative medicine. Among the molecular interactions and the pathways triggered during cell adhesion, the binding of cluster of differentiation 44 (CD44), a cell-surface glycoprotein involved in cell-cell interactions, to hyaluronic acid (HA), a major component of the extracellular matrix, is a crucial step. Cell therapy has emerged as a promising treatment for advanced liver diseases; however, so far, it has led to low cell engraftment and limited cell repopulation of the target tissue. Currently, different strategies are under investigation to improve cell grafting in the liver, including the use of organic and inorganic biomatrices that mimic the microenvironment of the extracellular matrix. Hyaluronans, major components of stem cell niches, are attractive candidates for coating stem cells since they improve viability, proliferation, and engraftment in damaged livers. In this review, we will discuss the new strategies that have been adopted to improve cell grafting and track cells after transplantation.

In Vivo Photoacoustic Tracking of Mesenchymal Stem Cell Viability.

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.

An Efficient T 1 Contrast Agent for Labeling and Tracking Human Embryonic Stem Cells on MRI.

Noninvasive cell tracking in vivo has the potential to advance stem cell-based therapies into the clinic. Magnetic resonance imaging (MRI) provides an excellent image-guidance platform; however, existing MR cell labeling agents are fraught with limited specificity. To address this unmet need, we developed a highly efficient manganese porphyrin contrast agent, MnEtP, using a two-step synthesis. In vitro MRI at 3 Tesla on human embryonic stem cells (hESCs) demonstrated high labeling efficiency at a very low dose of 10 µM MnEtP, resulting in a four-fold lower T 1 relaxation time. This extraordinarily low dose is ideal for labeling large cell numbers required for large animals and humans. Cell viability and differentiation capacity were unaffected. Cellular manganese quantification corroborated MRI findings, and the agent localized primarily on the cell membrane. In vivo MRI of transplanted hESCs in a rat demonstrated excellent sensitivity and specificity of MnEtP for noninvasive stem cell tracking.

Labeling Stem Cells with a New Hybrid Bismuth/Carbon Nanotube Contrast Agent for X-Ray Imaging.

The poor retention and survival of cells after transplantation to solid tissue represent a major obstacle for the effectiveness of stem cell-based therapies. The ability to track stem cells in vivo can lead to a better understanding of the biodistribution of transplanted cells, in addition to improving the analysis of stem cell therapies' outcomes. Here, we described the use of a carbon nanotube-based contrast agent (CA) for X-ray computed tomography (CT) imaging as an intracellular CA to label bone marrow-derived mesenchymal stem cells (MSCs). Porcine MSCs were labeled without observed cytotoxicity. The CA consists of a hybrid material containing ultra-short single-walled carbon nanotubes (20–80 nm in length, US-tubes) and Bi(III) oxo-salicylate clusters which contain four Bi3+ ions per cluster (Bi4C). The CA is thus abbreviated as Bi4C@US-tubes.

A standard procedure for lentiviral-mediated labeling of murine mesenchymal stromal cells in vitro.

Tracking of stem cells after transplantation is effectively performed in vivo with imaging systems, assuming the cells are adequately labeled to facilitate their recognition. This study aimed to optimize a protocol for fluorescent labeling of mesenchymal stromal cells (MSCs) in vitro, by using a third-generation lentiviral system. Basically, 293T cells are seeded in high-glucose Dulbecco's modified Eagle medium with 10% FBS one day before transfection. Transfection is done for 24h using a mix of transfer, packaging, regulatory, and envelope plasmids, in molar ratio of 4:2:1:1, respectively. After transfection, the cells are further cultured for two days. During this period, the viral medium is harvested two times, at 24-h intervals, with the first round being stored at 4°C until the second round is completed. The pooled viral medium is frozen in single-use aliquots. MSCs are transduced with 25 multiplicity of infection (MOI) and one day later the cells are passaged at standard seeding density and further grown for three days, when the fluorescence reach the maximum level. Our protocol provides particular experimental details for permanent MSC labeling that makes the procedure highly effective for therapeutic purposes, without affecting the functional properties of stem cells.

Carbon dots for in vivo fluorescence imaging of adipose tissue-derived mesenchymal stromal cells

Tissue regeneration based on stem cell therapy is one of the most rapidly developing fields of modern medicine. Several properties of human mesenchymal stromal cells (MSCs), such as tropism toward a tumor or injury site, make them promising candidates for regenerative medicine, targeted therapy, or treating injured tissues. However, to fully understand the role of stem cells in therapeutic function, their visualization in vivo is essential. Here, we describe, for the first time, the use of biocompatible quaternized carbon dots (QCDs) as a novel stem-cell tracking probe for in vivo fluorescence imaging of transplanted human MSCs. By studying the in vitro cytotoxicity, intracellular distribution, and precise uptake mechanism, we showed that QCDs had a high biocompatibility and excellent fluorescence properties after 24 h incubation with MSCs. Further to demonstrate the in vivo feasibility of the system, QCD-labeled MSCs (100 μg/mL of QCDs, 24 h incubation time) were transplanted subcutaneously into an immunodeficient mouse and visualized by optical in vivo imaging. The labeled cells were strongly fluorescent, allowing their semi-quantitative detection. Moreover, the homing of intravenously transplanted QCD-labeled MSCs into the solid tumor was clearly shown. The results demonstrated that QCD-labeling of human MSCs is a highly promising approach for in vivo tracking during stem cell therapy.

Tracking Stem Cell Implants in Cartilage Defects of Minipigs by Using Ferumoxytol-enhanced MRI.

Background Cartilage repair outcomes of matrix-associated stem cell implants (MASIs) in patients have been highly variable. Conventional MRI cannot help distinguish between grafts that will and grafts that will not repair the underlying cartilage defect until many months after the repair. Purpose To determine if ferumoxytol nanoparticle labeling could be used to depict successful or failed MASIs compared with conventional MRI in a large-animal model. Materials and Methods Between January 2016 and December 2017, 10 Göttingen minipigs (n = 5 male; n = 5 female; mean age, 6 months ± 5.1; age range, 4-20 months) received implants of unlabeled (n = 12) or ferumoxytol-labeled (n = 20) viable and apoptotic MASIs in cartilage defects of the distal femur. All MASIs were serially imaged with MRI on a 3.0-T imaging unit at week 1 and weeks 2, 4, 8, 12, and 24, with calculation of T2 relaxation times. Cartilage regeneration outcomes were assessed by using the MR observation of cartilage repair tissue (MOCART) score (scale, 0-100), the Pineda score, and histopathologic quantification of collagen 2 production in the cartilage defect. Findings were compared by using the unpaired Wilcoxon rank sum test, a linear regression model, the Fisher exact test, and Pearson correlation. Results Ferumoxytol-labeled MASIs showed significant T2 shortening (22.2 msec ± 3.2 vs 27.9 msec ± 1.8; P < .001) and no difference in cartilage repair outcomes compared with unlabeled control MASIs (P > .05). At week 2 after implantation, ferumoxytol-labeled apoptotic MASIs showed a loss of iron signal and higher T2 relaxation times compared with ferumoxytol-labeled viable MASIs (26.6 msec ± 4.9 vs 20.8 msec ± 5.3; P = .001). Standard MRI showed incomplete cartilage defect repair of apoptotic MASIs at 24 weeks. Iron signal loss at 2 weeks correlated with incomplete cartilage repair, diagnosed at histopathologic examination at 12-24 weeks. Conclusion Ferumoxytol nanoparticle labeling can accelerate the diagnosis of successful and failed matrix-associated stem cell implants at MRI in a large-animal model. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Sneag and Potter in this issue.

D-mannose-Coating of Maghemite Nanoparticles Improved Labeling of Neural Stem Cells and Allowed Their Visualization by ex vivo MRI after Transplantation in the Mouse Brain

Magnetic resonance imaging (MRI) of superparamagnetic iron oxide-labeled cells can be used as a non-invasive technique to track stem cells after transplantation. The aim of this study was to (1) evaluate labeling efficiency of D-mannose-coated maghemite nanoparticles (D-mannose(γ-Fe2O3)) in neural stem cells (NSCs) in comparison to the uncoated nanoparticles, (2) assess nanoparticle utilization as MRI contrast agent to visualize NSCs transplanted into the mouse brain, and (3) test nanoparticle biocompatibility. D-mannose(γ-Fe2O3) labeled the NSCs better than the uncoated nanoparticles. The labeled cells were visualized by ex vivo MRI and their localization subsequently confirmed on histological sections. Although the progenitor properties and differentiation of the NSCs were not affected by labeling, subtle effects on stem cells could be detected depending on dose increase, including changes in cell proliferation, viability, and neurosphere diameter. D-mannose coating of maghemite nanoparticles improved NSC labeling and allowed for NSC tracking by ex vivo MRI in the mouse brain, but further analysis of the eventual side effects might be necessary before translation to the clinic.

Listening for the therapeutic window: Advances in drug delivery utilizing photoacoustic imaging.

The preclinical landscape of photoacoustic imaging has experienced tremendous growth in the past decade. This non-invasive imaging modality augments the spatiotemporal capabilities of ultrasound with optical contrast. While it has principally been investigated for diagnostic applications, many recent reports have described theranostic delivery systems and drug monitoring strategies using photoacoustics. Here, we provide an overview of the progress to date while highlighting work in three specific areas: theranostic nanoparticles, real-time drug monitoring, and stem cell ("living drug") tracking. Additionally, we discuss the challenges that remain to be addressed in this burgeoning field.

A comprehensive toxicity evaluation of novel amino acid-modified magnetic ferrofluids for magnetic resonance imaging.

Stem cells have been widely exploited as remedial agents in regenerative medicine due to its tremendous potential in treatment of various debilitating diseases. In spite of this fact, there is need of a reliable, clinically applicable cell tracker for deciphering the homing and distribution of stem cells post-transplantation. Researchers have proposed the use of superparamagnetic magnetite (Fe3O4) nanoparticles for in vivo and in vitro tracking and imaging of stem cells. However, there is not much understanding of the chemical coatings on the nanoparticles, which is very important for the sustainability of stem cells in biological system. For any biomedical applications, the surface properties and the core structure of nanoparticles play a significant role. This study reports surface modification of magnetic Fe3O4 nanofluid with biocompatible amino acids viz., arginine and histidine to maintain colloidal stability at neutral pH, impart least disruption when encountered with the biological system and allow labeling with mesenchymal stem cells (MSCs). The size of amino acids-modified magnetic nanoferrofluid (AA@MNFs) was restricted to 15-25nm for enhanced uptake in stem cells. In vitro cytotoxicity profile of stem cells labeled AA@MNFs was estimated using various assays like MTT, LDH and AO/EtBr followed by detailed pre-clinical toxicity assessment of AA@MNFs which illustrated least toxicity effects in major tissues of the animals. In vitro MRI scans of the stem cells labeled AA@MNFs confirmed the suitability of the reported ferrofluids for the use as MR contrast agents.