scholarly journals [18F]FDG-labelled stem cell PET imaging in different route of administrations and multiple animal species

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naoko Nose ◽  
Suguru Nogami ◽  
Kazuhiro Koshino ◽  
Xinyu Chen ◽  
Rudolf A. Werner ◽  
...  

AbstractStem cell therapy holds great promise for tissue regeneration and cancer treatment, although its efficacy is still inconclusive and requires further understanding and optimization of the procedures. Non-invasive cell tracking can provide an important opportunity to monitor in vivo cell distribution in living subjects. Here, using a combination of positron emission tomography (PET) and in vitro 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) direct cell labelling, the feasibility of engrafted stem cell monitoring was tested in multiple animal species. Human mesenchymal stem cells (MSCs) were incubated with phosphate-buffered saline containing [18F]FDG for in vitro cell radiolabelling. The pre-labelled MSCs were administrated via peripheral vein in a mouse (n = 1), rats (n = 4), rabbits (n = 4) and non-human primates (n = 3), via carotid artery in rats (n = 4) and non-human primates (n = 3), and via intra-myocardial injection in rats (n = 5). PET imaging was started 10 min after cell administration using a dedicated small animal PET system for a mouse and rats. A clinical PET system was used for the imaging of rabbits and non-human primates. After MSC administration via peripheral vein, PET imaging revealed intense radiotracer signal from the lung in all tested animal species including mouse, rat, rabbit, and non-human primate, suggesting administrated MSCs were trapped in the lung tissue. Furthermore, the distribution of the PET signal significantly differed based on the route of cell administration. Administration via carotid artery showed the highest activity in the head, and intra-myocardial injection increased signal from the heart. In vitro [18F]FDG MSC pre-labelling for PET imaging is feasible and allows non-invasive visualization of initial cell distribution after different routes of cell administration in multiple animal models. Those results highlight the potential use of that imaging approach for the understanding and optimization of stem cell therapy in translational research.

2015 ◽  
Vol 3 (16) ◽  
pp. 3848-3859 ◽  
Author(s):  
Waleed Ahmed El-Said ◽  
Seung U. Kim ◽  
Jeong-Woo Choi

Neuro-cell chip was developed for non-invasive monitoring of neural stem cell stimulation using SERS technique that enabled the real-time monitoring, which is important for tissue development protocols.


2021 ◽  
Author(s):  
Jin Ding ◽  
Qian Zhang ◽  
Jinquan Jiang ◽  
Nina Zhou ◽  
Zilei Wang ◽  
...  

Abstract Angiotensin-converting enzyme 2 (ACE2), a transmembrane protein, is the main entry point for certain coronaviruses including the new coronavirus SARS-CoV-2 to enter cells. Synthesizing the PET imaging probe Al18F-DX600-BCH which is high-affinity ACE2 is aim to detect the expression of ACE2 in body and monitor the therapeutic effect. The Al18F-DX600-BCH was obtained manually with a 20.4% ± 5.2% radiochemical yield without attenuation correction and an over 99% purified radiochemical purity, being stable in vitro within 4 hours and cleared rapidly in blood (the half-lives of the distribution phase and clearance phase were 2.12 min and 25.31 min, respectively). Results of both biodistribution and PET imaging showed that Al18F-DX600-BCH was highly accumulated in the kidney (SUVkidney/normal > 50), and specific uptake in testis (SUVtestis/normal > 10) was observed in rat images. The kidney (++), gastrointestinal (++) and bronchial (+++) cells were evidenced of ACE2 positive by IHC staining of rats. A total of 10 volunteers were enrolled and received PET/CT 1 hour and 2 hours after injection or dynamic PET/CT during 0-330 seconds (NCT04542863), from which strong radioactivity accumulation was mostly observed in the genitourinary system (SUVrenal cortex = 32.00, SUVtestis = 4.56), and moderate accumulation in conjunctiva and nasal mucosa for several cases. This work firstly reported the probe Al18F-DX600-BCH targeting ACE2, conducting preliminary preclinical experiments and a total of 10 clinical transformations, which demonstrated the potential and possibility of non-invasive mapping of ACE2. Trial registration: ClinicalTrials.gov NCT04542863. Registered 9 September 2020.


2016 ◽  
Vol 87 (2) ◽  
pp. 024301 ◽  
Author(s):  
Katarzyna Anna Radaszkiewicz ◽  
Dominika Sýkorová ◽  
Pavel Karas ◽  
Jana Kudová ◽  
Lukáš Kohút ◽  
...  

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Bertrand Pain

AbstractOrganoids are three-dimensional structures that are derived from the self-organization of stem cells as they differentiate in vitro. The plasticity of stem cells is one of the major criteria for generating organoids most similar to the tissue structures they intend to mimic. Stem cells are cells with unique properties of self-renewal and differentiation. Depending on their origin, a distinction is made between pluripotent (embryonic) stem cells (PSCs), adult (or tissue) stem cells (ASCs), and those obtained by somatic reprogramming, so-called induced pluripotent stem cells (iPSCs). While most data since the 1980s have been acquired in the mouse model, and then from the late 1990s in humans, the process of somatic reprogammation has revolutionized the field of stem cell research. For domestic animals, numerous attempts have been made to obtain PSCs and iPSCs, an approach that makes it possible to omit the use of embryos to derive the cells. Even if the plasticity of the cells obtained is not always optimal, the recent progress in obtaining reprogrammed cells is encouraging. Along with PSCs and iPSCs, many organoid derivations in animal species are currently obtained from ASCs. In this study, we present state-of-the-art stem cell research according to their origins in the various animal models developed.


2021 ◽  
Vol 28 ◽  
Author(s):  
Sanjeev Gautam ◽  
Sangita Biswas ◽  
Birbal Singh ◽  
Ying Guo ◽  
Peng Deng ◽  
...  

: There is a momentous surge in the development of stem cell technology as a therapeutic and diagnostic tools. Stem cell-derived cells are currently used in various clinical trials. However, key issues and challenges involve the low differentiation efficiency, integration, and functioning of transplanted stem cells-derived cells. Extraction of bone marrow, adipose, or other mesenchymal stem cells (MSCs) involves invasive methods, specialized skills, and expensive technologies. Urine-derived cells, on the other hand, are obtained by non-invasive methods. Samples can be obtained repeatedly from patients of any age. Urine-derived cells are used to generate reprogrammed or induced pluripotent stem cells (iPSCs), which can be cultured, and differentiated into various types of cell lineages for biomedical investigations and drug testing in vitro or in vivo using model animals of human diseases. Urine cell-derived iPSCs (UiPSCs) have emerged as a major area of research and immense therapeutic significance. Given that preliminary preclinical studies are successful in terms of safety and as a regenerative tool, the UiPSCs will pave the way to develop and expedite various types of autologous stem cell therapies.


2019 ◽  
Vol 26 (11) ◽  
pp. 815-828 ◽  
Author(s):  
Afaf Aldahish ◽  
Ajay Kale ◽  
Ahmed Aljameeli ◽  
Girish V Shah

Stem cell-like-cancer cells are key drivers of tumor growth, metastasis, and relapse of cancer following remission. Prostate stem cell-like cancer cells isolated from human prostate cancer (PC) biopsies express CD44+/α2β1 hi/CD133+ cell surface markers and can self-renew in vitro. Expression of calcitonin (CT) and its receptor (CTR) is frequently elevated in PCs and activation of CT-CTR axis in non-invasive PC cells induces an invasive phenotype. We investigated whether CT-CTR autocrine axis induces stem cell-like phenotype in two PC cell lines. CT-CTR axis in these cell lines was activated by enforced expression of CTR. The cells were then examined for the changes in the expression of CD44 and CD133, collagen adherence, tumorigenic, metastatic and repopulating characteristics. The activation of CT-CTR axis led to a large increase in adherence to collagen and a remarkable increase of CD44 and CD133 in PC-3 and LNCaP cells. This was accompanied by a strong increase in tumorigenic, metastatic and repopulation properties of PC cells. However, the mutation of CTR-C PDZ-binding site in CTR almost abolished CTR-mediated increases in stem cell-like characteristics of PC cells. These results support an important role for CT-CTR axis in the progression of PC from localized cancer to an aggressive form, and a majority of proinvasive CTR actions may be mediated through its interaction with its partner protein at the PDZ-binding site. These results suggest that CT/CTR can serve as a valuable target to prevent the generation of stem-like PC cells.


2021 ◽  
Vol 8 ◽  
Author(s):  
Maximilian Fischer ◽  
Mathias J. Zacherl ◽  
Ludwig Weckbach ◽  
Lisa Paintmayer ◽  
Tobias Weinberger ◽  
...  

Cardiac monitoring after murine myocardial infarction, using serial non-invasive cardiac 18F-FDG positron emissions tomography (PET) represents a suitable and accurate tool for in vivo studies. Cardiac PET imaging enables tracking metabolic alterations, heart function parameters and provides correlations of the infarct size to histology. ECG-gated 18F-FDG PET scans using a dedicated small-animal PET scanner were performed in mice at baseline, 3, 14, and 30 days after myocardial infarct (MI) by permanent ligation of the left anterior descending (LAD) artery. The percentage of the injected dose per gram (%ID/g) in the heart, left ventricular metabolic volume (LVMV), myocardial defect, and left ventricular function parameters: end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and the ejection fraction (EF%) were estimated. PET assessment of the defect positively correlates with post-infarct histology at 3 and 30 days. Infarcted murine hearts show an immediate decrease in LVMV and an increase in %ID/g early after infarction, diminishing in the remodeling process. This study of serial cardiac PET scans provides insight for murine myocardial infarction models by novel infarct surrogate parameters. It depicts that serial PET imaging is a valid, accurate, and multimodal non-invasive assessment.


1991 ◽  
Vol 66 (03) ◽  
pp. 355-360 ◽  
Author(s):  
Harve C Wilson ◽  
William Coffman ◽  
Anne L Killam ◽  
Marlene L Cohen

SummaryThe present study was designed to evaluate the effectiveness of the ergoline 5HT2 receptor antagonist, LY53857 in a rabbit model of vascular arterial occlusion. LY53857 (1 and 10 εM) inhibited serotonin amplified platelet aggregation responses to threshold concentrations of ADP in rabbit platelets in vitro. LY53857 (1 εM) not only inhibited the serotonin component of rabbit platelet aggregation, but also inhibited in vitro aggregation induced by ADP (48.7 ± 16.7% inhibition), collagen (76.1 ± 15.9% inhibition) and U46619 (65.2 ± 12.3% inhibition). The effectiveness of this ergoline 5HT2 receptor antagonist in blocking aggregation to ADP, collagen and U46619 may be related to its ability to inhibit a serotonin component of platelet aggregation since rabbit platelets possess high concentrations of serotonin that may be released during aggregation produced by other agents. Based on the effectiveness of LY53857 to inhibit rabbit platelet aggregation, we explored the ability of LY53857 to extend the time to carotid artery occlusion in rabbits following electrical stimulation of the artery. Reproducible carotid artery occlusion was induced in rabbits by moderate stenosis coupled to arterial cross clamping, followed by electrical stimulation. With this procedure, occlusion occurred at 47.0 ± 7 min (n = 30) after initiation of the electrical stimulation. Animals pretreated with LY53857 (50 to 500 εg/kg i.v.) showed a delay in the time to carotid artery occlusion (at 100 εg/kg i.v. occlusion time extended to 164 ± 16 min). Furthermore, ex vivo platelet aggregation from animals treated with LY53857 (300 εg/kg i.v.) resulted in 40.5% inhibition of platelet aggregation in response to the combination of ADP (1 εM) and serotonin (1 εM). These studies document the ability to obtain reproducible arterial occlusion in the rabbit and showed that intravenously administered LY53857 prolonged the time to carotid artery occlusion. Prolongation of carotid artery occlusion time was accompanied by inhibition of serotonin-amplified ADP-induced aggregation in rabbit platelets, an effect observed both in vitro and ex vivo. Thus, the rabbit is a useful model for studying the effectiveness of 5HT2 receptor antagonists in prolonging vascular occlusion induced by insult of the carotid artery.


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