Abstract 5283: Perfluorocarbon Microcapsules for X-ray Visualization of Mesenchymal Stem Cell Delivery and Engraftment

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Yingli Fu ◽  
Dorota Kedziorek ◽  
Veronica Crisostomo ◽  
Wesley Gilson ◽  
Nicole Azene ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Tracking ◽  
Therapeutic Angiogenesis ◽  
Cell Delivery ◽  
Intramyocardial Injection ◽  
X Ray ◽  
Stem Cell Delivery

Mesenchymal stem cell (MSC) transplantation offers an alternative strategy for therapeutic angiogenesis for the management of ischemic cardiovascular disease. However, the poor survival of transplanted cells and lack of sustained engraftment severely limits therapeutic efficacy. We propose a novel cell microencapsulation method utilizing perfluoro-octyl-bromide (PFOB) impregnated alginate-poly-L-lysine-alginate microcapsules (PFOB Caps) that enable noninvasive cell delivery and tracking using conventional clinical X-ray fluoroscopy. Microen-capsulation of rabbit MSCs (1x10 6 cells/ml) combined with PFOB-loaded alginate was performed with an electrostatic droplet generator. Control capsules lacked PFOB. MSC viability post-encapsulation was determined using a microfluorometric assay. X-ray fluoroscopy was performed during direct intramuscular/intramyocardial injection of 2300 capsules/injection in a rabbit peripheral arterial disease (PAD) model (n=2) and a swine reperfused myocardial infarction (MI) model (n=3). Fluoroscopy and angiographic computed tomography (DynaCT) were performed to assess the ability to monitor microcapsule delivery and tracking with X-ray. As compared to control capsules, PFOB Caps showed similar swelling, when subjected to 55 mM sodium citrate incubation (mean diameter increased 5.4% for PFOB vs. 4.5% for control, P=NS), and mechanical strength (broken capsules from osmotic pressure tests: 2/591 for PFOB and 2/603 for control). The PFOB Caps showed a small viability decrease immediately after encapsulation (90±3%) with no significant further viability loss up to 4 weeks in vitro (79±5%). In both PAD and MI animals, successful injection of PFOB Caps could be demonstrated with DynaCT but not with real-time fluoroscopic images. Control capsules were never detected. CT tracking of PFOB Caps was possible up to 5 weeks post-injection. PFOB microcapsules provide an ideal microenvironment for maintaining MSC viability in vitro . In addition, PFOB proves to be a non-toxic, radiopaque agent suitable for cell tracking using conventional fluoroscopy in vivo . PFOB microencapsulation of MSCs may be a novel approach for X-ray tracking therapeutic angiogenesis.

Abstract 527: A Novel Stem Cell Delivery Model for Evaluation of Delivery Using Targeted Bifunctional Liposomes with Ultrasound Enhancement

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Ali K Naji ◽  
Michael Wassler ◽  
George Britton ◽  
Harnath S Shelat ◽  
Yong-Jian Geng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Targeted Delivery ◽  
Color Doppler ◽  
Color Doppler Ultrasound ◽  
Cell Delivery ◽  
Stem Cell Delivery ◽  
Vitro Model

Introduction. We have developed bifunctional echogenic liposomes (BF-ELIP) targeted to both CD34 and ICAM-1 to facilitate delivery of CD34+ stem cells to inflammatory endothelium. We previously confirmed that BF-ELIP enhanced CD34+ stem cell adherence to ICAM-1-expressing endothelium in vitro and in vivo and showed that ultrasound (US) facilitated penetration of stem cells into the endothelial cell layer. Hypothesis. The transwell culture system can serve as an in vitro model for study of US-enhanced targeted delivery of stem cells to atheroma. Methods. BF-ELIP were prepared by evaporation-rehydration-sonication-lyophilization, followed by conjugating antibodies specific for CD34 and ICAM-1 through a thioether linkage. TNFα-pretreated HUVEC monolayers on transwell (6 wells/plate) insert membranes were incubated with nonspecific IgG-ELIP or BF-ELIP (1mg/well) for 15 minutes, followed by human monocytes labeled with Oregon Green. Half the inserts were subjected to 6 MHz color Doppler ultrasound (MI = 0.4) for 5 minutes. Fluorescence of resuspended cells was measured after treatment of both inserts and wells with 0.25% trypsin/0.1% EDTA 24 hours later. Results. BF-ELIP enhanced adherence of monocytes to the ICAM-1-expressing HUVEC monolayer relative to untreated controls and IgG-ELIP, but did not increase the number (Fig. 1) or proportion (Fig. 2) of monocytes traversing the monolayer. US greatly increased the number of monocytes both adhering to and passing through the monolayer in all groups. Conclusions. We have succeeded in developing a transwell cultured HUVEC system as a model for US-enhanced, BF-ELIP-mediated stem cell delivery to inflammatory endothelium.

scholarly journals Non-surgical stem cell delivery strategies and in vivo cell tracking to injured myocardium

2010 ◽  
Vol 27 (3) ◽  
pp. 367-383 ◽  
Author(s):  
Tycho I. G. van der Spoel ◽  
Joe Chun-Tsu Lee ◽  
Krijn Vrijsen ◽  
Joost P. G. Sluijter ◽  
Maarten Jan M. Cramer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Tracking ◽  
Cell Delivery ◽  
Stem Cell Delivery ◽  
Injured Myocardium ◽  
Delivery Strategies

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

scholarly journals Mesenchymal Stem Cell Delivery of TRAIL Can Eliminate Metastatic Cancer

2009 ◽  
Vol 69 (10) ◽  
pp. 4134-4142 ◽  
Author(s):  
Michael R. Loebinger ◽  
Ayad Eddaoudi ◽  
Derek Davies ◽  
Sam M. Janes
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Metastatic Cancer ◽  
Cell Delivery ◽  
Stem Cell Delivery

Aggregate mesenchymal stem cell delivery ameliorates the regenerative niche for muscle repair

2018 ◽  
Vol 12 (8) ◽  
pp. 1867-1876 ◽  
Author(s):  
Marissa A. Ruehle ◽  
Hazel Y. Stevens ◽  
Aaron M. Beedle ◽  
Robert E. Guldberg ◽  
Jarrod A. Call
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Cell Delivery ◽  
Muscle Repair ◽  
Stem Cell Delivery

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.

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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