scholarly journals Radiopharmaceutical Stem Cell Tracking for Neurological Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Paulo Henrique Rosado-de-Castro ◽  
Pedro Moreno Pimentel-Coelho ◽  
Bianca Gutfilen ◽  
Sergio Augusto Lopes de Souza ◽  
Gabriel Rodriguez de Freitas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Tracking ◽  
Imaging Techniques ◽  
Neurological Diseases ◽  
Cell Labeling ◽  
Pharmacological Agents ◽  
Cell Therapies ◽  
Causes Of Disease ◽  
Potential Applications

Although neurological ailments continue to be some of the main causes of disease burden in the world, current therapies such as pharmacological agents have limited potential in the restoration of neural functions. Cell therapies, firstly applied to treat different hematological diseases, are now being investigated in preclinical and clinical studies for neurological illnesses. However, the potential applications and mechanisms for such treatments are still poorly comprehended and are the focus of permanent research. In this setting, noninvasivein vivoimaging allows better understanding of several aspects of stem cell therapies. Amongst the various methods available, radioisotope cell labeling has become one of the most promising since it permits tracking of cells after injection by different routes to investigate their biodistribution. A significant increase in the number of studies utilizing this method has occurred in the last years. Here, we review the different radiopharmaceuticals, imaging techniques, and findings of the preclinical and clinical reports published up to now. Moreover, we discuss the limitations and future applications of radioisotope cell labeling in the field of cell transplantation for neurological diseases.

Non-radioactive imaging strategies for in vivo immune cell tracking

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Łukasz Kiraga ◽  
Paulina Kucharzewska ◽  
Damian Strzemecki ◽  
Tomasz P. Rygiel ◽  
Magdalena Król
Keyword(s):  
Diagnostic Imaging ◽  
Contrast Agents ◽  
Cell Tracking ◽  
Immune Cell ◽  
Imaging Techniques ◽  
Diagnostic Technique ◽  
Cell Labeling ◽  
X Ray Imaging ◽  
Disease Study

Abstract In vivo tracking of administered cells chosen for specific disease treatment may be conducted by diagnostic imaging techniques preceded by cell labeling with special contrast agents. The most commonly used agents are those with radioactive properties, however their use in research is often impossible. This review paper focuses on the essential aspect of cell tracking with the exclusion of radioisotope tracers, therefore we compare application of different types of non-radioactive contrast agents (cell tracers), methods of cell labeling and application of various techniques for cell tracking, which are commonly used in preclinical or clinical studies. We discuss diagnostic imaging methods belonging to three groups: (1) Contrast-enhanced X-ray imaging, (2) Magnetic resonance imaging, and (3) Optical imaging. In addition, we present some interesting data from our own research on tracking immune cell with the use of discussed methods. Finally, we introduce an algorithm which may be useful for researchers planning leukocyte targeting studies, which may help to choose the appropriate cell type, contrast agent and diagnostic technique for particular disease study.

Abstract 1767: Feasibility of In Vivo Cardiac Stem Cell Tracking, by SPECT and PET Imaging, Using the Sodium-iodide Symporter as Reporter Gene

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
John Terrovitis ◽  
Keng Fai Kwok ◽  
Riikka Läutamaki ◽  
James M Engles ◽  
Andreas S Barth ◽  
...  
Keyword(s):  
Stem Cell ◽  
Reporter Gene ◽  
Cell Tracking ◽  
Ex Vivo ◽  
Small Animal ◽  
Cell Labeling ◽  
Sodium Iodide Symporter ◽  
Cell Injection

Background. Stem cells offer the promise of cardiac repair. Stem cell labeling is a prerequisite to tracking cell fate in vivo . Aim. To develop a reporter gene that permits in vivo stem cell labeling. We examined the sodium-iodide symporter (NIS), a protein that is not expressed in the heart, but promotes cellular uptake of 99m Tc or 124 I, thus permitting cell tracking by SPECT or PET imaging, respectively. Methods. The human NIS gene ( h NIS) was expressed in rat cardiac derived stem cells (rCDCs) using lentivirus driven by the CAG or CMV promoter. NIS function in transduced cells was confirmed by in vitro 99m Tc uptake. Eleven rats were injected with 1 or 2 million rCDCs intramyocardially immediately after LAD ligation; 6 with CMV-NIS and 5 with CAG-NIS cells. Dual isotope SPECT imaging was performed on a small animal SPECT/CT system, using 99m Tc for cell detection and 201 Tl for myocardial delineation, 24 hrs after cell injection. PET was performed on a small animal PET scanner using 124 I for cell tracking and 13 NH 3 for myocardial delineation, 48hrs after cell injection. Contrast Ratio (CR) was defined as [(signal in the cells)-(signal in blood pool)]/signal in blood pool. High resolution ex vivo SPECT scans of explanted hearts (n=3) were obtained to confirm that in vivo signal was derived from the cell injection site. The presence of h NIS mRNA was confirmed in injected hearts after animal sacrifice (n=2), by real-time RT-PCR. Results. NIS expression in rCDCs did not affect cell viability/proliferation (p=0.718, ctr vs NIS). In vitro 99m Tc uptake was 6.0±0.9% vs 0.07±0.05, without and with perchlorate (specific NIS blocker), respectively. NIS-transduced rCDCs were easily visualized as spots of 99m Tc or 124 I uptake within a perfusion deficit in the SPECT and PET images. CR was considerably higher when cells were transduced by the CMV-NIS virus in comparison to the CAG-NIS virus (70±40% vs 28±29%, p=0.085). Ex vivo small animal SPECT imaging confirmed that in vivo 99m Tc signals were localized to the injection sites. PCR confirmed the presence of h NIS mRNA in injected hearts. Conclusion. NIS expression allows non invasive in vivo stem cell tracking in the myocardium, using both SPECT and PET. This reporter gene has great potential for translation in future clinical applications.

scholarly journals In Vivo Assessment of Stem Cells for Treating Neurodegenerative Disease: Current Approaches and Future Prospects

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Byeong-Wook Song
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neurodegenerative Disease ◽  
Cell Tracking ◽  
Imaging Techniques ◽  
Three Dimensional ◽  
Research Area ◽  
In Vivo Experiments ◽  
And Migration

In recent years, stem cell-related therapies have been widely applied for treating neurodegenerative disease. Despite their potential, stem cell tracking and imaging techniques for the evaluation of in vivo proof-of-concept (PoC) therapies have not been sufficiently represented in the research area. This review summarizes the recent approaches that have been used for tracking and imaging engrafted stem cells in vivo. Furthermore, we introduce tissue clearing technology that can be applied to develop three-dimensional in vivo experiments. Monitoring stem cell survival and migration and graft-host relationships is a useful strategy to evaluate the therapeutic efficacy of regenerative medicine approaches in neurodegenerative disease.

scholarly journals Stem Cell Tracking Technologies for Neurological Regenerative Medicine Purposes

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yongtao Zheng ◽  
Jiongwei Huang ◽  
Tongming Zhu ◽  
Ronggang Li ◽  
Zhifu Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Tracking ◽  
Multimodality Imaging ◽  
Image Resolution ◽  
The Body ◽  
Imaging Method ◽  
Nuclear Medicine Imaging ◽  
Migration Routes ◽  
Cell Therapies

The growing field of stem cell therapy is moving toward clinical trials in a variety of applications, particularly for neurological diseases. However, this translation of cell therapies into humans has prompted a need to create innovative and breakthrough methods for stem cell tracing, to explore the migration routes and its reciprocity with microenvironment targets in the body, to monitor and track the outcome after stem cell transplantation therapy, and to track the distribution and cell viability of transplanted cells noninvasively and longitudinally. Recently, a larger number of cell tracking methods in vivo were developed and applied in animals and humans, including magnetic resonance imaging, nuclear medicine imaging, and optical imaging. This review has been intended to summarize the current use of those imaging tools in tracking stem cells, detailing their main features and drawbacks, including image resolution, tissue penetrating depth, and biosafety aspects. Finally, we address that multimodality imaging method will be a more potential tracking tool in the future clinical application.

scholarly journals Simplified 89Zr-Labeling Protocol of Oxine (8-Hydroxyquinoline) Enabling Prolonged Tracking of Liposome-Based Nanomedicines and Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1097
Author(s):  
Andras Polyak ◽  
Jens P. Bankstahl ◽  
Karen F. W. Besecke ◽  
Constantin Hozsa ◽  
Wiebke Triebert ◽  
...  
Keyword(s):  
Reaction Times ◽  
Extraction Methods ◽  
Cell Labeling ◽  
Size Exclusion ◽  
Cell Therapies ◽  
Biodistribution Studies ◽  
Positron Emission ◽  
Human Ipscs ◽  
Radiochemical Yields

In this work, a method for the preparation of the highly lipophilic labeling synthon [89Zr]Zr(oxinate)4 was optimized for the radiolabeling of liposomes and human induced pluripotent stem cells (hiPSCs). The aim was to establish a robust and reliable labeling protocol for enabling up to one week positron emission tomography (PET) tracing of lipid-based nanomedicines and transplanted or injected cells, respectively. [89Zr]Zr(oxinate)4 was prepared from oxine (8-hydroxyquinoline) and [89Zr]Zr(OH)2(C2O4). Earlier introduced liquid–liquid extraction methods were simplified by the optimization of buffering, pH, temperature and reaction times. For quality control, thin-layer chromatography (TLC), size-exclusion chromatography (SEC) and centrifugation were employed. Subsequently, the 89Zr-complex was incorporated into liposome formulations. PET/CT imaging of 89Zr-labeled liposomes was performed in healthy mice. Cell labeling was accomplished in PBS using suspensions of 3 × 106 hiPSCs, each. [89Zr]Zr(oxinate)4 was synthesized in very high radiochemical yields of 98.7% (96.8% ± 2.8%). Similarly, high internalization rates (≥90%) of [89Zr]Zr(oxinate)4 into liposomes were obtained over an 18 h incubation period. MicroPET and biodistribution studies confirmed the labeled nanocarriers’ in vivo stability. Human iPSCs incorporated the labeling agent within 30 min with ~50% efficiency. Prolonged PET imaging is an ideal tool in the development of lipid-based nanocarriers for drug delivery and cell therapies. To this end, a reliable and reproducible 89Zr radiolabeling method was developed and tested successfully in a model liposome system and in hiPSCs alike.

scholarly journals Improved biocompatibility and efficient labeling of neural stem cells with poly(L-lysine)-coated maghemite nanoparticles

2016 ◽  
Vol 7 ◽  
pp. 926-936 ◽  
Author(s):  
Igor M Pongrac ◽  
Marina Dobrivojević ◽  
Lada Brkić Ahmed ◽  
Michal Babič ◽  
Miroslav Šlouf ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Neural Stem Cells ◽  
Cellular Uptake ◽  
Cell Tracking ◽  
Cellular Migration ◽  
Cell Labeling ◽  
Blue Staining ◽  
Maghemite Nanoparticles ◽  
Acetoxymethyl Ester

Background: Cell tracking is a powerful tool to understand cellular migration, dynamics, homing and function of stem cell transplants. Nanoparticles represent possible stem cell tracers, but they differ in cellular uptake and side effects. Their properties can be modified by coating with different biocompatible polymers. To test if a coating polymer, poly(L-lysine), can improve the biocompatibility of nanoparticles applied to neural stem cells, poly(L-lysine)-coated maghemite nanoparticles were prepared and characterized. We evaluated their cellular uptake, the mechanism of internalization, cytotoxicity, viability and proliferation of neural stem cells, and compared them to the commercially available dextran-coated nanomag®-D-spio nanoparticles. Results: Light microscopy of Prussian blue staining revealed a concentration-dependent intracellular uptake of iron oxide in neural stem cells. The methyl thiazolyl tetrazolium assay and the calcein acetoxymethyl ester/propidium iodide assay demonstrated that poly(L-lysine)-coated maghemite nanoparticles scored better than nanomag®-D-spio in cell labeling efficiency, viability and proliferation of neural stem cells. Cytochalasine D blocked the cellular uptake of nanoparticles indicating an actin-dependent process, such as macropinocytosis, to be the internalization mechanism for both nanoparticle types. Finally, immunocytochemistry analysis of neural stem cells after treatment with poly(L-lysine)-coated maghemite and nanomag®-D-spio nanoparticles showed that they preserve their identity as neural stem cells and their potential to differentiate into all three major neural cell types (neurons, astrocytes and oligodendrocytes). Conclusion: Improved biocompatibility and efficient cell labeling makes poly(L-lysine)-coated maghemite nanoparticles appropriate candidates for future neural stem cell in vivo tracking studies.

Inorganic Nanoparticles and Nanomaterials Based on Titanium (Ti): Applications in Medicine

2013 ◽  
Vol 754 ◽  
pp. 21-87 ◽  
Author(s):  
Zeid A. Al Othman ◽  
Mohammad Mezbaul Alam ◽  
Mu. Naushad ◽  
Inamuddin ◽  
Mohd Farhan Khan
Keyword(s):  
Drug Delivery ◽  
Gene Delivery ◽  
Cell Tracking ◽  
Conventional Medicine ◽  
Inorganic Nanoparticles ◽  
Cell Labeling ◽  
Body Parts ◽  
Drug And Gene Delivery

Nanomedicine is a relatively new field of science and technology. By interacting with biomolecules, therefore at nanoscale, nanotechnology opens up a vast field of research and application. Current and potential applications of nanotechnology in medicine range from research involving diagnostic devices, drug delivery vehicles to enhanced gene therapy and tissue engineering procedures. Its advantage over conventional medicine lies on its size. Operating at nanoscale allows to exploit physical properties different from those observed at microscale such as the volume/surface ratio. This allows drugs of nanosize be used in lower concentration and has an earlier onset of therapeutic action. It also provides materials for controlled drug delivery by directing carriers to a specific location. Inorganic nanomedicine is likely to remain one of the most prolific fields of nanomedicine, which refers to the use of inorganic or hybrid (inorganic-inorganic or inorganic-organic) nanomaterials (INMs) and nanoparticles (INPs) to achieve innovative medical advances for body parts implantation, drug and gene discovery and delivery, discovery of biomarkers, and molecular diagnostics. Among the most promising INMs being developed are metal, silica, dendrimers, organic-inorganic hybrids, ceramics (e.g. ZrO2, TiO2, Al2O3, etc.) and bioinorganic hybrids. Metal NP contrast agents enhance magnetic resonance imaging and ultrasound results in biomedical applications of in vivo imaging. Hollow and porous INMs have been exploited for drug and gene delivery, diagnostic imaging, and photothermal therapy. Biomolecular inorganic nanohybrids and nanostructured biomaterials have been exploited for targeted imaging and therapy, drug and gene delivery, and regenerative medicine. Potential uses for fluorescent quantum dots (QDs) include cell labeling, biosensing, in vivo imaging, bimodal magnetic-luminescent imaging, and diagnostics. Biocompatible QD conjugates have been used successfully for sentinel lymph node mapping, tumor targeting, tumor angiogenesis imaging, and metastasis cell tracking. This article outlines present developments and future prospects for the use of Ti-based NPs and NMs in experimental in vivo and in vitro studies and in engineering nanodevices and biosensors for clinical and investigative use in diagnosis and therapy in diverse fields of medical sciences, such as oncology, infection control, orthopedics, dentistry, dermatology, genetics, cardiology, ophthalmology, etc. Toxicological considerations of these INPs and INMs are also discussed.

scholarly journals Whole-Body Imaging to Assess Cell-Based Immunotherapy: Preclinical Studies with an Update on Clinical Translation

2021 ◽  
Author(s):  
Noriko Sato ◽  
Peter L. Choyke
Keyword(s):  
T Cell ◽  
Cell Tracking ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Clinical Translation ◽  
Whole Body ◽  
Whole Body Imaging ◽  
Body Imaging ◽  
Cell Therapies

AbstractIn the past decades, immunotherapies against cancers made impressive progress. Immunotherapy includes a broad range of interventions that can be separated into two major groups: cell-based immunotherapies, such as adoptive T cell therapies and stem cell therapies, and immunomodulatory molecular therapies such as checkpoint inhibitors and cytokine therapies. Genetic engineering techniques that transduce T cells with a cancer-antigen-specific T cell receptor or chimeric antigen receptor have expanded to other cell types, and further modulation of the cells to enhance cancer targeting properties has been explored. Because cell-based immunotherapies rely on cells migrating to target organs or tissues, there is a growing interest in imaging technologies that non-invasively monitor transferred cells in vivo. Here, we review whole-body imaging methods to assess cell-based immunotherapy using a variety of examples. Following a review of preclinically used cell tracking technologies, we consider the status of their clinical translation.

Systematic Intracellular Biocompatibility Assessments of Superparamagnetic Iron Oxide Nanoparticles in Human Umbilical Cord Mesenchyme Stem Cells in Testifying Its Reusability for Inner Cell Tracking by MRI

2019 ◽  
Vol 15 (11) ◽  
pp. 2179-2192
Author(s):  
Yuanyuan Xie ◽  
Wei Liu ◽  
Bing Zhang ◽  
Bin Wang ◽  
Liudi Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Umbilical Cord ◽  
Cell Tracking ◽  
Superparamagnetic Iron Oxide ◽  
Human Umbilical Cord ◽  
Cell Based Therapy

Until now, there is no effective method for tracking transplanted stem cells in human. Ruicun (RC) is a new ultra-small SPIONs agent that has been approved by China Food and Drug Administration for iron supplementation but not as a stem cell tracer in clinic. In this study, we demonstrated magnetic resonance imaging-based tracking of RC-labeled human umbilical cord derived mesenchymal stem cells (MSCs) transplanted to locally injured site of rat spinal cords. We then comprehensively evaluated the safety and quality of the RC-labeled MSCs under good manufacturing practicecompliant conditions, to investigate the feasibility of SPIONs for inner tracking in stem cell-based therapy (SCT). Our results showed that RC labeling at appropriate dose (200 μg/mL) did not have evident impacts on characteristics of MSCs in vitro, demonstrating safety, non-carcinogenesis, and non-tissue inflammation in vivo. The systematic assessments of intracellular biocompatibility indicated that the RC labeled MSCs met with mandatory requirements and standards for law-regulation systems regarding SCT, facilitating translation of cell-tracking technologies to clinical trials.

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