Multi-modal Cell Labelling for Quantification and Optimization of Stem Cell Delivery to Orthotopic Breast Tumors

2019 ◽  
Author(s):  
May Zaw Thin ◽  
Robin Bofinger ◽  
Tomas D. Kostelec ◽  
John Connell ◽  
P. Stephen Patrick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Viability ◽  
Photon Emission ◽  
Breast Tumors ◽  
Whole Body ◽  
Cell Delivery ◽  
Cell Labelling ◽  
Cell Localization ◽  
Stem Cell Delivery

Stem cells have been utilized as anti-cancer agents due to their ability to home to and integrate within tumors. Methods to augment stem cell homing to tumors are being investigated with the goal of enhancing treatment efficacy. However, it is currently not possible to evaluate both cell localization and cell viability after engraftment, hindering optimization of therapy. In this study, luciferase expressing human adipocyte derived stem cells (ADSCs) were labelled with superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to Indium-111 to produce cells with tri-modal imaging capabilities. ADSCs were administered intravenously (IV) or intracardially (IC) to mice bearing 4T1 orthotopic breast tumors. Cell fate was monitored serially using bioluminescence imaging (BLI) as a measure of cell viability, magnetic resonance imaging (MRI) for cell localization and single photon emission computer tomography (SPECT) for cell quantification. BLI/MRI/SPECT imaging revealed differences in whole body cell distribution between injection routes. BLI showed the presence of viable ADSCs within tumors as early as 1-hour post IC injection compared to 3 days post IV injection. SPECT data showed the percentage of ADSCs within tumors to be 2-fold higher after IC than IV at 5-hour post injection. Whereas, MRI confirmed the localization of SPION labelled cells in tumors after IC injection but not IV. Finally, histological analysis was used to validate engraftment of ADSC within tumor tissue. These findings demonstrate that multi-modal imaging can be used to evaluate the efficiency of stem cell delivery to tumors and that IC cell administration is more effective for tumor targeting.<br>

Multi-modal Cell Labelling for Quantification and Optimization of Stem Cell Delivery to Orthotopic Breast Tumors

2019 ◽  
Author(s):  
May Zaw Thin ◽  
Robin Bofinger ◽  
Tomas D. Kostelec ◽  
John Connell ◽  
P. Stephen Patrick ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Viability ◽  
Photon Emission ◽  
Breast Tumors ◽  
Whole Body ◽  
Cell Delivery ◽  
Cell Labelling ◽  
Cell Localization ◽  
Stem Cell Delivery

Stem cells have been utilized as anti-cancer agents due to their ability to home to and integrate within tumors. Methods to augment stem cell homing to tumors are being investigated with the goal of enhancing treatment efficacy. However, it is currently not possible to evaluate both cell localization and cell viability after engraftment, hindering optimization of therapy. In this study, luciferase expressing human adipocyte derived stem cells (ADSCs) were labelled with superparamagnetic iron oxide nanoparticles (SPIONs) conjugated to Indium-111 to produce cells with tri-modal imaging capabilities. ADSCs were administered intravenously (IV) or intracardially (IC) to mice bearing 4T1 orthotopic breast tumors. Cell fate was monitored serially using bioluminescence imaging (BLI) as a measure of cell viability, magnetic resonance imaging (MRI) for cell localization and single photon emission computer tomography (SPECT) for cell quantification. BLI/MRI/SPECT imaging revealed differences in whole body cell distribution between injection routes. BLI showed the presence of viable ADSCs within tumors as early as 1-hour post IC injection compared to 3 days post IV injection. SPECT data showed the percentage of ADSCs within tumors to be 2-fold higher after IC than IV at 5-hour post injection. Whereas, MRI confirmed the localization of SPION labelled cells in tumors after IC injection but not IV. Finally, histological analysis was used to validate engraftment of ADSC within tumor tissue. These findings demonstrate that multi-modal imaging can be used to evaluate the efficiency of stem cell delivery to tumors and that IC cell administration is more effective for tumor targeting.<br>

scholarly journals Multi-modal imaging probe for assessing the efficiency of stem cell delivery to orthotopic breast tumours

Nanoscale ◽  
2020 ◽  
Vol 12 (31) ◽  
pp. 16570-16585 ◽  
Author(s):  
May Zaw Thin ◽  
Helen Allan ◽  
Robin Bofinger ◽  
Tomas D. Kostelec ◽  
Simon Guillaume ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Delivery ◽  
Adipose Derived Stem Cells ◽  
Breast Tumours ◽  
Imaging Probe ◽  
Stem Cell Delivery

Illustration of adipose-derived stem cells with tri-modal imaging capabilities for evaluating the efficiency of cell delivery to tumours.

Engineered Cell Sheets for the Effective Delivery of Adipose-Derived Stem Cells for Tendon-to-Bone Healing

2020 ◽  
Vol 48 (13) ◽  
pp. 3347-3358
Author(s):  
Myung Jin Shin ◽  
In Kyong Shim ◽  
Dong Min Kim ◽  
Jae Hee Choi ◽  
Yu Na Lee ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Bone Healing ◽  
Cell Sheet ◽  
The Other ◽  
Cell Delivery ◽  
Micro Ct ◽  
Stem Cell Delivery ◽  
Effective Delivery ◽  
Repair Group

Background: Efforts are being made to treat rotator cuff tears (RCTs) that exhibit poor healing and high retear rates. Tendon-to-bone healing using mesenchymal stem cells is being explored, but research is needed to establish effective delivery options. Purpose: To evaluate the effects of an adipose-derived stem cell (ADSC) sheet on mesenchymal stem cell delivery for tendon-to-bone healing of a chronic RCT in rats and to demonstrate that ADSC sheets enhance tendon-to-bone healing. Study Design: Controlled laboratory study. Methods: Mesenchymal stem cells were obtained from rat adipose tissue, and a cell sheet was prepared using a temperature-responsive dish. To evaluate the efficacy of stem cells produced in a sheet for the lesion, the experiment was conducted with 3 groups: repair group, cell sheet transplantation after repair group, and cell sheet–only group. Histological, biomechanical, and micro–computed tomography (micro-CT) results were compared among the groups. Results: Hematoxylin and eosin staining for histomorphological analysis revealed that the cell sheet transplantation after repair group (5.75 ± 0.95) showed statistically significant higher scores than the repair (2.75 ± 0.50) and cell sheet–only (3.25 ± 0.50) groups ( P < .001). On safranin O staining, the cell sheet transplantation after repair group (0.51 ± 0.04 mm2) had a larger fibrocartilage area than the repair (0.31 ± 0.06 mm2) and cell sheet–only (0.32 ± 0.03 mm2) groups ( P = .001). On micro-CT, bone volume/total volume values were significantly higher in the cell sheet transplantation after repair group (23.98% ± 1.75%) than in the other groups ( P < .039); there was no significant difference in the other values. On the biomechanical test, the cell sheet transplantation after repair group (4 weeks after repair) showed significantly higher results than the other groups ( P < .005). Conclusion: Our study shows that engineered stem cells are a clinically feasible stem cell delivery tool for rotator cuff repair. Clinical Relevance: This laboratory study provides evidence that ADSCs are effective in repairing RCTs, which are common sports injuries.

scholarly journals Progenitor/Stem Cell Delivery by Suprarenal Aorta Route in Acute Kidney Injury

2019 ◽  
Vol 28 (11) ◽  
pp. 1390-1403 ◽  
Author(s):  
Érika B. Rangel ◽  
Samirah A. Gomes ◽  
Rosemeire Kanashiro-Takeuchi ◽  
Joshua M. Hare
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Arteries ◽  
Cell Delivery ◽  
Chronic Injury ◽  
Stem Cell Delivery ◽  
Suprarenal Aorta

Progenitor/stem cell-based kidney regenerative strategies are a key step towards the development of novel therapeutic regimens for kidney disease treatment. However, the route of cell delivery, e.g., intravenous, intra-arterial, or intra-parenchymal, may affect the efficiency for kidney repair in different models of acute and chronic injury. Here, we describe a protocol of intra-aorta progenitor/stem cell injection in rats following either acute ischemia-reperfusion injury or acute proteinuria induced by puromycin aminonucleoside (PAN) – the experimental prototype of human minimal change disease and early stages of focal and segmental glomerulosclerosis. Vascular clips were applied across both renal pedicles for 35 min, or a single dose of PAN was injected via intra-peritoneal route, respectively. Subsequently, 2 x 106 stem cells [green fluorescent protein (GFP)-labeled c-Kit+ progenitor/stem cells or GFP-mesenchymal stem cells] or saline were injected into the suprarenal aorta, above the renal arteries, after application of a vascular clip to the abdominal aorta below the renal arteries. This approach contributed to engraftment rates of ∼10% at day 8 post ischemia-reperfusion injury, when c-Kit+ progenitor/stem cells were injected, which accelerated kidney recovery. Similar rates of engraftment were found after PAN-induced podocyte damage at day 21. With practice and gentle surgical technique, 100% of the rats could be injected successfully, and, in the week following injection, ∼ 85% of the injected rats will recover completely. Given the similarities in mammals, much of the data obtained from intra-arterial delivery of progenitor/stem cells in rodents can be tested in translational research and clinical trials with endovascular catheters in humans.

scholarly journals Recent Progress in Stem Cell Modification for Cardiac Regeneration

2018 ◽  
Vol 2018 ◽  
pp. 1-22 ◽  
Author(s):  
Heiko Lemcke ◽  
Natalia Voronina ◽  
Gustav Steinhoff ◽  
Robert David
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Adult Stem Cells ◽  
Embryonic Stem ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Cell Delivery ◽  
Regenerative Capacity ◽  
Stem Cell Delivery ◽  
Cell Based Therapy

During the past decades, stem cell-based therapy has acquired a promising role in regenerative medicine. The application of novel cell therapeutics for the treatment of cardiovascular diseases could potentially achieve the ambitious aim of effective cardiac regeneration. Despite the highly positive results from preclinical studies, data from phase I/II clinical trials are inconsistent and the improvement of cardiac remodeling and heart performance was found to be quite limited. The major issues which cardiac stem cell therapy is facing include inefficient cell delivery to the site of injury, accompanied by low cell retention and weak effectiveness of remaining stem cells in tissue regeneration. According to preclinical and clinical studies, various stem cells (adult stem cells, embryonic stem cells, and induced pluripotent stem cells) represent the most promising cell types so far. Beside the selection of the appropriate cell type, researchers have developed several strategies to produce “second-generation” stem cell products with improved regenerative capacity. Genetic and nongenetic modifications, chemical and physical preconditioning, and the application of biomaterials were found to significantly enhance the regenerative capacity of transplanted stem cells. In this review, we will give an overview of the recent developments in stem cell engineering with the goal to facilitate stem cell delivery and to promote their cardiac regenerative activity.

Delivery of mesenchymal stem cells for tackling systemic disorders

2021 ◽  
Vol 16 ◽  
Author(s):  
Wing-Fu Lai
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Tissue Repair ◽  
Current Status ◽  
Cell Delivery ◽  
Stem Cell Delivery ◽  
Technological Advances ◽  
Degenerative Disorders ◽  
Multiple Injured ◽  
The Moment

: Development of methods of manipulating and culturing stem cells has enabled the emergence of stem cell therapy as a promising approach in diverse applications, ranging from tissue repair to treatment of intractable diseases such as diabetes, cardiovascular diseases and neurological disorders. Along with technological advances in systemic stem cell delivery, treating multiple injured or pathological sites simultaneously has been made possible. Despite this, most of the works on systemic stem cell transplantation at the moment have focused on the efficiency of tackling local disorders. The prospect of the therapy for enhancing systemic tissue repair, as well as for tackling systemic degenerative disorders, has rarely been seriously considered. The objective of this article is to fill this gap by reviewing the current status of research on systemic stem cell delivery, and by presenting the opportunities and challenges for translating systemic stem cell delivery from the laboratory to the clinic.

Cell-laden alginate/polyacrylamide beads as carriers for stem cell delivery: preparation and characterization

RSC Advances ◽  
2016 ◽  
Vol 6 (25) ◽  
pp. 20475-20484 ◽  
Author(s):  
Deepti Rana ◽  
Aleya Tabasum ◽  
Murugan Ramalingam
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Delivery ◽  
Polymeric Gel ◽  
Stem Cell Delivery ◽  
3D Morphology ◽  
Gel System

The rationale behind present investigation was to enhance the encapsulation efficacy of stem cells within the polymeric gel system and retain their 3D morphology as in the native microenvironment.

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 Regenerative capacity of bone marrow stem cells with or without superparamagnetic iron oxide nanoparticles after facial nerve degeneration: A narrative review

2021 ◽  
Vol 20 (3) ◽  
pp. 300-304
Author(s):  
Noura Abd El-Latif ◽  
◽  
Mona Denewar ◽  
Rehab R. El-Zehary ◽  
Fatma M. Ibrahim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Facial Nerve ◽  
Superparamagnetic Iron Oxide ◽  
The Body ◽  
Cell Delivery ◽  
Oxide Nanoparticles ◽  
Magnetic Targeting ◽  
Stem Cell Delivery

Facial palsy can be defined as a kind of paralysis affecting facial muscles. It is termed Bell’s palsy if it is unilateral. It may occur due to trauma to the facial nerve, infections as herpes zoster, neoplastic lesions, or unknown cause. It may be also associated with metabolic and systemic diseases as hypertension, toxicity, amyloidosis, alcoholism, auto-immune diseases and diabetes mellitus. Mesenchymal stem cells (MSCs) are multipotent adult stromal cells that have many benefits as an evolving treatment modality. Bone marrow stem cells (BMSCs) divide progressively in culture, and differentiate into neurons exclusively with use of a simple protocol. Most ongoing preclinical and clinical cell treatment modalities composed of local or systemic transplantation of stem or progenitor cells. In addition, they depend on the migration and retention of transplanted cells at insult areas. Nevertheless, one of the main obstacles against this modality is how to detect the fate and exact location of these cells inside the body, and how to maintain the cells at this specific site. Magnetic targeting systems, which depends on cells labelled by magnetic carriers, have been assessed as a more efficient technique for stem cell delivery to target sites. These systems depend on loading stem cells with magnetic nanoparticles and attracting them to the exact intended area within the body by placing an external magnetic field. Superparamagnetic iron oxide nanoparticles (SPIONs) have been introduced in the last few years as a rising applicant of nanoparticles in a vast variety of medical fields as magnetic separation, drug delivery, magnetic resonance imaging (MRI) and magnetic hyperthermia. In addition, applications of SPIONs, as a site-specific drug carrier, diagnostic agent and stem cell delivery agent, receive most attention of researchers in that field. In this review, up-to-date information about Magnetic targeting of degenerated facial nerve by BMSCs labelled with SPIONs may suggest its capacity of better regeneration than injection of BMSCs alone.

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