scholarly journals Ultrasensitive in Vivo Fluorescence Imaging of Mesenchymal Stem Cells and Small Molecule-Induced Pluripotent Stem Cells in BALB/c mice.

2021 ◽  
Author(s):  
Sang Yeon Lee ◽  
Ho-Seong Han ◽  
Sang Tae Kim ◽  
Tae Hyun Kim ◽  
Kye Ho Lee
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Injection Site ◽  
Small Molecule ◽  
Pluripotent Stem Cells ◽  
Clinical Studies ◽  
Human Mesenchymal Stem Cells ◽  
Multipotent Stem Cells ◽  
The Brain

Abstract BackgroundMesenchymal cell has been frequently used in clinical studies. Mesenchymal stem cells (MSCs) are self-renewing, multipotent stem cells with the potential to differentiate into multiple mesoderm lineages. But MSC have limitation in clinical application for treating human diseases because they can differentiate several types of cell but not all types. PSL (Pluripotent Stem cell Like cell) are newly developed pluripotent stem cells from human mesenchymal stem cells (hMSC) induced by small molecule compounds. These cells have potential advantages for clinical cell treatment compared with ESCs and iPSCs.MethodsWe induced pluripotency from MSC using small molecules. It has tried to trace MSC and PSL in mice using bioluminescent techniques, which can detect visible light emitted from cells labeled with miRNA conjugated fluorescent molecules. ResultsMSCs predominantly migrate into the brain and testis. They also migrate to the liver, omentum, mesentery, kidneys and spleen. Migration of PSL is similar to MSCs, in that they go to the brain, testis and other intraperitoneal organs. Fluorescent images of explanted organs show that the intensity of brain images is higher in the PSL mouse group than the MSC mouse group. However, testis, image intensity is higher in MSC mouse group than the PSL mouse group. In PSL but not MSC mice, fluorescence persisted at the injection site in the tail.ConclusionsIn this study, injected MSCs and PSL predominantly migrated to the brain and testis. But, PSL migration was more than MSC migration in Brain. Both cell types had a similar migration pattern except for persistent fluorescence at injection site in the tail vein of PSL mice. We expect these cell therapy may have many potentials for clinical studies on these notable treatments.

scholarly journals Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Virginia Egea ◽  
Kai Kessenbrock ◽  
Devon Lawson ◽  
Alexander Bartelt ◽  
Christian Weber ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Human Mesenchymal Stem Cells ◽  
Target Cells ◽  
Autophagic Flux ◽  
Stromal Cell Derived Factor

AbstractBone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.

Migration of Human Mesenchymal Stem Cells is Stimulated by Low Shear Stress via MAPK Signaling

2012 ◽  
Author(s):  
Lin Yuan ◽  
Naoya Sakamoto ◽  
Guanbin Song ◽  
Masaaki Sato
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Mapk Signaling ◽  
Disease Treatment ◽  
Differentiation Potential ◽  
Multipotent Stem Cells ◽  
Low Shear Stress ◽  
Multipotent Differentiation ◽  
And Migration

Mesenchymal stem cells (MSCs) represent as multipotent stem cells which hold the abilities of self-renewal and give rise to cells of diverse lineages [1]. With their remarkable combination of multipotent differentiation potential and low immunogenicity, MSCs are considered to be an attractive candidate for cell-based tissue repair and regenerative tissue engineering [2, 3]. Increasing number of studies has demonstrated that mobilization and migration of injected MSCs to the damaged tissues is a key step for these cells to participate in disease treatment and tissue regeneration [4, 5].

Characterization of patient-derived bone marrow human mesenchymal stem cells as oncolytic virus carriers for the treatment of glioblastoma

2021 ◽  
pp. 1-11
Author(s):  
Yuzaburo Shimizu ◽  
Joy Gumin ◽  
Feng Gao ◽  
Anwar Hossain ◽  
Elizabeth J. Shpall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Human Mesenchymal Stem Cells ◽  
Oncolytic Viruses ◽  
In Vivo Studies ◽  
Systemic Delivery ◽  
Previously Treated

OBJECTIVE Delta-24-RGD is an oncolytic adenovirus that is capable of replicating in and killing human glioma cells. Although intratumoral delivery of Delta-24-RGD can be effective, systemic delivery would improve its clinical application. Bone marrow–derived human mesenchymal stem cells (BM-hMSCs) obtained from healthy donors have been investigated as virus carriers. However, it is unclear whether BM-hMSCs can be derived from glioma patients previously treated with marrow-toxic chemotherapy or whether such BM-hMSCs can deliver oncolytic viruses effectively. Herein, the authors undertook a prospective clinical trial to determine the feasibility of obtaining BM-hMSCs from patients with recurrent malignant glioma who were previously exposed to marrow-toxic chemotherapy. METHODS The authors enrolled 5 consecutive patients who had been treated with radiation therapy and chemotherapy. BM aspirates were obtained from the iliac crest and were cultured to obtain BM-hMSCs. RESULTS The patient-derived BM-hMSCs (PD-BM-hMSCs) had a morphology similar to that of healthy donor–derived BM-hMSCs (HD-BM-hMSCs). Flow cytometry revealed that all 5 cell lines expressed canonical MSC surface markers. Importantly, these cultures could be made to differentiate into osteocytes, adipocytes, and chondrocytes. In all cases, the PD-BM-hMSCs homed to intracranial glioma xenografts in mice after intracarotid delivery as effectively as HD-BM-hMSCs. The PD-BM-hMSCs loaded with Delta-24-RGD (PD-BM-MSC-D24) effectively eradicated human gliomas in vitro. In in vivo studies, intravascular administration of PD-BM-MSC-D24 increased the survival of mice harboring U87MG gliomas. CONCLUSIONS The authors conclude that BM-hMSCs can be acquired from patients previously treated with marrow-toxic chemotherapy and that these PD-BM-hMSCs are effective carriers for oncolytic viruses.

scholarly journals Large-Scale Expansion of Human Mesenchymal Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-17 ◽  
Author(s):  
Muhammad Najib Fathi Bin Hassan ◽  
Muhammad Dain Yazid ◽  
Mohd Heikal Mohd Yunus ◽  
Shiplu Roy Chowdhury ◽  
Yogeswaran Lokanathan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Large Scale ◽  
Human Mesenchymal Stem Cells ◽  
Expansion Ratio ◽  
Spinner Flask ◽  
Roller Bottle ◽  
Multipotent Stem Cells ◽  
Cardiovascular Damage ◽  
Scale Expansion

Mesenchymal stem cells (MSCs) are multipotent stem cells with strong immunosuppressive property that renders them an attractive source of cells for cell therapy. MSCs have been studied in multiple clinical trials to treat liver diseases, peripheral nerve damage, graft-versus-host disease, autoimmune diseases, diabetes mellitus, and cardiovascular damage. Millions to hundred millions of MSCs are required per patient depending on the disease, route of administration, frequency of administration, and patient body weight. Multiple large-scale cell expansion strategies have been described in the literature to fetch the cell quantity required for the therapy. In this review, bioprocessing strategies for large-scale expansion of MSCs were systematically reviewed and discussed. The literature search in Medline and Scopus databases identified 26 articles that met the inclusion criteria and were included in this review. These articles described the large-scale expansion of 7 different sources of MSCs using 4 different bioprocessing strategies, i.e., bioreactor, spinner flask, roller bottle, and multilayered flask. The bioreactor, spinner flask, and multilayered flask were more commonly used to upscale the MSCs compared to the roller bottle. Generally, a higher expansion ratio was achieved with the bioreactor and multilayered flask. Importantly, regardless of the bioprocessing strategies, the expanded MSCs were able to maintain its phenotype and potency. In summary, the bioreactor, spinner flask, roller bottle, and multilayered flask can be used for large-scale expansion of MSCs without compromising the cell quality.

scholarly journals Canonical Wnts function as potent regulators of osteogenesis by human mesenchymal stem cells

2009 ◽  
Vol 185 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Guizhong Liu ◽  
Sapna Vijayakumar ◽  
Luca Grumolato ◽  
Randy Arroyave ◽  
HuiFang Qiao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Bone Formation ◽  
Wnt Signaling ◽  
De Novo ◽  
Human Mesenchymal Stem Cells ◽  
Mitogen Activated Protein Kinase ◽  
Bone Homeostasis

Genetic evidence indicates that Wnt signaling is critically involved in bone homeostasis. In this study, we investigated the functions of canonical Wnts on differentiation of adult multipotent human mesenchymal stem cells (hMSCs) in vitro and in vivo. We observe differential sensitivities of hMSCs to Wnt inhibition of osteogenesis versus adipogenesis, which favors osteoblastic commitment under binary in vitro differentiation conditions. Wnt inhibition of osteogenesis is associated with decreased expression of osteoblastic transcription factors and inhibition of c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation, which are involved in osteogenic differentiation. An hMSC subpopulation exhibits high endogenous Wnt signaling, the inhibition of which enhances osteogenic and adipogenic differentiation in vitro. In an in vivo bone formation model, high levels of Wnt signaling inhibit de novo bone formation by hMSCs. However, hMSCs with exogenous expression of Wnt1 but not stabilized β-catenin markedly stimulate bone formation by naive hMSCs, arguing for an important role of a canonical Wnt gradient in hMSC osteogenesis in vivo.

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