scholarly journals CD73 Expression on Mesenchymal Stem Cells Dictates the Reparative Properties via Its Anti-Inflammatory Activity

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Kezhe Tan ◽  
Hongtao Zhu ◽  
Jianfang Zhang ◽  
Weili Ouyang ◽  
Jianfeng Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Inflammatory Activity ◽  
Cell Based Therapy ◽  
Pericardial Adipose Tissue ◽  
Anti Inflammatory ◽  
Cd73 Expression ◽  
Cultivation In Vitro

Mesenchymal stem cells (MSC) are not universal and may be subject to dynamic changes upon local milieus in vivo and after isolation and cultivation in vitro. Here, we demonstrate that MSC derived from murine pericardial adipose tissue (pMSC) constitute two cohorts of population distinguished by the level of CD73 expression (termed as CD73high and CD73low pMSC). Transplantation of two types of cells into mouse hearts after myocardial infarction (MI) revealed that the CD73high pMSC preferentially brought about structural and functional repair in comparison to the PBS control and CD73low pMSC. Furthermore, the CD73high pMSC displayed a pronounced anti-inflammatory activity by attenuating CCR2+ macrophage infiltration and upregulating several anti-inflammatory genes 5 days after in vivo transplantation and ex vivo cocultivation with peritoneal macrophages. The immunomodulatory effect was not seen in cocultivation experiments with pMSC derived from CD73 knockout mice (CD73-/-) but was partially blocked by pretreatment of the A2b receptor antagonist, PSB603. The results highlight a heterogeneity of the CD73 expression that may be related to its catalytic products on the modulation of the local immune response and thus provide a possible explanation to the inconsistency of the regenerative results when different sources of donor cells were used in stem cell-based therapy.

scholarly journals Mesenchymal stem cells accelerated growth and metastasis of neuroblastoma and preferentially homed towards both primary and metastatic loci in orthotopic neuroblastoma model

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiao-Le Yu ◽  
Shing Chan ◽  
Marcus Kwong-Lam Fung ◽  
Godfrey Chi-Fung Chan
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Primary Tumor ◽  
Imaging System ◽  
Ex Vivo ◽  
Tumor Formation ◽  
Human Neuroblastoma Cell ◽  
Fluorescence Signal ◽  
Human Neuroblastoma

Abstract Background Majority of neuroblastoma patients develop metastatic disease at diagnosis and their prognosis is poor with current therapeutic approach. Major challenges are how to tackle the mechanisms responsible for tumorigenesis and metastasis. Human mesenchymal stem cells (hMSCs) may be actively involved in the constitution of cancer microenvironment. Methods An orthotopic neuroblastoma murine model was utilized to mimic the clinical scenario. Human neuroblastoma cell line SK-N-LP was transfected with luciferase gene, which were inoculated with/without hMSCs into the adrenal area of SCID-beige mice. The growth and metastasis of neuroblastoma was observed by using Xenogen IVIS 100 in vivo imaging and evaluating gross tumors ex vivo. The homing of hMSCs towards tumor was analyzed by tracing fluorescence signal tagged on hMSCs using CRI Maestro™ imaging system. Results hMSCs mixed with neuroblastoma cells significantly accelerated tumor growth and apparently enhanced metastasis of neuroblastoma in vivo. hMSCs could be recruited by primary tumor and also become part of the tumor microenvironment in the metastatic lesion. The metastatic potential was consistently reduced in lung and tumor when hMSCs were pre-treated with stromal cell derived factor-1 (SDF-1) blocker, AMD3100, suggesting that the SDF-1/CXCR4 axis was one of the prime movers in the metastatic process. Conclusions hMSCs accelerated and facilitated tumor formation, growth and metastasis. Furthermore, the homing propensity of hMSCs towards both primary tumor and metastatic loci can also provide new therapeutic insights in utilizing bio-engineered hMSCs as vehicles for targeted anti-cancer therapy.

Anti-nociceptive and anti-inflammatory activity of synthesized novel benzoxazole derivatives

2021 ◽  
Vol 20 ◽  
Author(s):  
Mansi L. Patil ◽  
Swati S. Gaikwad ◽  
Naresh J. Gaikwad
Keyword(s):  
Cytotoxic Activity ◽  
Research Study ◽  
Ex Vivo ◽  
Immunological Response ◽  
Inflammatory Activity ◽  
Inflammatory Drugs ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Introduction: Pain is an immunological response to any infection or inflammation and long term use of pain management therapy includes use of Nonsteroidal anti-inflammatory drugs which is associated with occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. Aims: The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods. Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds was carried out. Results: The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effect along significantly higher cytotoxic activity in MCF-7 cell lines. Conclusion: It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti-nociceptive and anti-inflammatory effect along with cytotoxic activity and certain modification in structure may result in potent activity.

scholarly journals Mesenchymal Stem Cells Exhibit Both a Proinflammatory and Anti-Inflammatory Effect on Saccular Aneurysm Formation in a Rabbit Model

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Michael B. Avery ◽  
Brooke L. Belanger ◽  
Amy Bromley ◽  
Arindom Sen ◽  
Alim P. Mitha
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Rabbit Model ◽  
Potential Interaction ◽  
Allogenic Bone ◽  
Aneurysm Formation ◽  
Vehicle Injection ◽  
Anti Inflammatory

Several studies have demonstrated a potential interaction between mesenchymal stem cells (MSCs) and saccular aneurysms. In this study, we sought to determine whether allogenic bone marrow-derived MSCs had the ability to prevent aneurysm formation in a known rabbit elastase aneurysm model. MSCs were injected intravenously in experimental rabbits at the time of surgical creation and two weeks postcreation and compared with control rabbits receiving vehicle injection. Angiography was used to compare aneurysm measurements four weeks postcreation, and aneurysms were harvested for histological properties. Serum was collected longitudinally to evaluate cytokine alterations. Serum from control animals was also utilized to perform in vitro tests with MSCs to compare the effect of the serologic environment in animals with and without aneurysms on MSC proliferation and cytokine production. While aneurysm morphometric comparisons revealed no differences, significant cytokine alterations were observed in vitro and in vivo, suggesting both anti-inflammatory and proinflammatory processes were occurring in the presence of MSCs. Histological analyses suggested that tunica intima hyperplasia was inhibited in the presence of MSCs.

scholarly journals Transduction of Bone-Marrow-Derived Mesenchymal Stem Cells by Using Lentivirus Vectors Pseudotyped with Modified RD114 Envelope Glycoproteins

2004 ◽  
Vol 78 (3) ◽  
pp. 1219-1229 ◽  
Author(s):  
Xian-Yang Zhang ◽  
Vincent F. La Russa ◽  
Jakob Reiser
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Ex Vivo ◽  
Leukemia Virus ◽  
Human Mscs ◽  
Systemic Delivery ◽  
Endogenous Virus ◽  
Hiv 1

ABSTRACT Bone-marrow-derived mesenchymal stem cells (MSCs) have attracted considerable attention as tools for the systemic delivery of therapeutic proteins in vivo, and the ability to efficiently transfer genes of interest into such cells would create a number of therapeutic opportunities. We have designed and tested a series of human immunodeficiency virus type 1 (HIV-1)-based vectors and vectors based on the oncogenic murine stem cell virus to deliver and express transgenes in human MSCs. These vectors were pseudotyped with either the vesicular stomatitis virus G (VSV-G) glycoprotein (GP) or the feline endogenous virus RD114 envelope GP. Transduction efficiencies and transgene expression levels in MSCs were analyzed by quantitative flow cytometry and quantitative real-time PCR. While transduction efficiencies with virus particles pseudotyped with the VSV-G GP were found to be high, RD114 pseudotypes revealed transduction efficiencies that were 1 to 2 orders of magnitude below those observed with VSV-G pseudotypes. However, chimeric RD114 GPs, with the transmembrane and extracellular domains fused to the cytoplasmic domain derived from the amphotropic Moloney murine leukemia virus 4070A GP, revealed about 15-fold higher titers relative to the unmodified RD114 GP. The transduction efficiencies in human MSCs of HIV-1-based vectors pseudotyped with the chimeric RD114 GP were similar to those obtained with HIV-1 vectors pseudotyped with the VSV-G GP. Our results also indicate that RD114 pseudotypes were less toxic than VSV-G pseudotypes in human MSC progenitor assays. Taken together, these results suggest that lentivirus pseudotypes bearing alternative Env GPs provide efficient tools for ex vivo modification of human MSCs.

Application of Mesenchymal Stem Cells Derived From the Umbilical Cord Instead of Bone Marrow In Hematopoietic Stem Cells Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4544-4544
Author(s):  
Ching-Tien Peng
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Proliferative Potential ◽  
Hematopoietic Stem ◽  
Cell Based Therapy

Abstract Abstract 4544 Bone marrow-derived mesenchymal stem cells (BMMSCs) have been found to enhance engraftment of hematopoietic stem cell transplantation (HSCT), plus show effect against graft-versus host disease (GVHD) because of their immunosuppressive properties. However, harvesting these cells is an invasive and painful procedure. To substitute BMMSCs from alternative sources is necessary. We intravenously infused ex vivo-expanded third-party umbilical cord-derived mesenchymal stem cells (UCMSCs) obtained from a bank 8 times in 3 patients who developed severe, steroid-resistant acute GVHD after allogeneic HSCT. The acute GVHD improved with each infusion of UCMSCs. Besides, after cotransplantation of cord blood and UCMSCs in 5 patients, we found UCMSCs enhanced absolute neutrophil counts and platelet counts recovery. No adverse effects after UCMSCs infusions were noted. We also found that UCMSCs had superior proliferative potential and greater immunosuppressive effects than BMMSCs in vitro. This is the first report of UCMSCs in human clinical application. These findings suggest UCMSCs are effective in treating aGVHD and can enhance hematopoiesis after HSCT. Considering that they are not only easy to obtain but also proliferate rapidly, UCMSCs would be the ideal candidate for cell-based therapy, especially for diseases associated with immune responses because of their immunosuppressive effects. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Anti-Inflammatory Fibronectin-AgNP for Regulation of Biological Performance and Endothelial Differentiation Ability of Mesenchymal Stem Cells

2021 ◽  
Vol 22 (17) ◽  
pp. 9262
Author(s):  
Huey-Shan Hung ◽  
Kai-Bo Chang ◽  
Cheng-Ming Tang ◽  
Tian-Ren Ku ◽  
Mei-Lang Kung ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Silver Nanoparticles ◽  
Mesenchymal Stem Cells ◽  
Superior Performance ◽  
In Vivo Studies ◽  
Vascular Regeneration ◽  
Anti Inflammatory

The engineering of vascular regeneration still involves barriers that need to be conquered. In the current study, a novel nanocomposite comprising of fibronectin (denoted as FN) and a small amount of silver nanoparticles (AgNP, ~15.1, ~30.2 or ~75.5 ppm) was developed and its biological function and biocompatibility in Wharton’s jelly-derived mesenchymal stem cells (MSCs) and rat models was investigated. The surface morphology as well as chemical composition for pure FN and the FN-AgNP nanocomposites incorporating various amounts of AgNP were firstly characterized by atomic force microscopy (AFM), UV-Visible spectroscopy (UV-Vis), and Fourier-transform infrared spectroscopy (FTIR). Among the nanocomposites, FN-AgNP with 30.2 ppm silver nanoparticles demonstrated the best biocompatibility as assessed through intracellular ROS production, proliferation of MSCs, and monocytes activation. The expression levels of pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were also examined. FN-AgNP 30.2 ppm significantly inhibited pro-inflammatory cytokine expression compared to other materials, indicating superior performance of anti-immune response. Mechanistically, FN-AgNP 30.2 ppm significantly induced greater expression of vascular endothelial growth factor (VEGF) and stromal-cell derived factor-1 alpha (SDF-1α) and promoted the migration of MSCs through matrix metalloproteinase (MMP) signaling pathway. Besides, in vitro and in vivo studies indicated that FN-AgNP 30.2 ppm stimulated greater protein expressions of CD31 and von Willebrand Factor (vWF) as well as facilitated better endothelialization capacity than other materials. Furthermore, the histological tissue examination revealed the lowest capsule formation and collagen deposition in rat subcutaneous implantation of FN-AgNP 30.2 ppm. In conclusion, FN-AgNP nanocomposites may facilitate the migration and proliferation of MSCs, induce endothelial cell differentiation, and attenuate immune response. These finding also suggests that FN-AgNP may be a potential anti-inflammatory surface modification strategy for vascular biomaterials.

scholarly journals Sorbaria kirilowii Ethanol Extract Exerts Anti-Inflammatory Effects In Vitro and In Vivo by Targeting Src/Nuclear Factor (NF)-κB

Biomolecules ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 741 ◽  
Author(s):  
Jiwon Jang ◽  
Jong Sub Lee ◽  
Young-Jin Jang ◽  
Eui Su Choung ◽  
Wan Yi Li ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Ex Vivo ◽  
Ethanol Extract ◽  
Inflammatory Activity ◽  
No Production ◽  
Nuclear Factor ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Inflammation is a fundamental process for defending against foreign antigens that involves various transcriptional regulatory processes as well as molecular signaling pathways. Despite its protective roles in the human body, the activation of inflammation may also convey various diseases including autoimmune disease and cancer. Sorbaria kirilowii is a plant originating from Asia, with no anti-inflammatory activity reported. In this paper, we discovered an anti-inflammatory effect of S. kirilowii ethanol extract (Sk-EE) both in vivo and in vitro. In vitro effects of Sk-EE were determined with lipopolysaccharide (LPS)-stimulated RAW264.7 cells, while ex vivo analysis was performed using peritoneal macrophages of thioglycollate (TG)-induced mice. Sk-EE significantly reduced the nitric oxide (NO) production of induced macrophages and inhibited the expression of inflammation-related cytokines and the activation of transcription factors. Moreover, treatment with Sk-EE also decreased the activation of proteins involved in nuclear factor (NF)-κB signaling cascade; among them, Src was a prime target of Sk-EE. For in vivo assessment of the anti-inflammatory effect of Sk-EE, HCl/EtOH was given by the oral route to mice for gastritis induction. Sk-EE injection dose-dependently reduced the inflammatory lesion area of the stomach in gastritis-induced mice. Taking these results together, Sk-EE exerts its anti-inflammatory activity by regulating intracellular NF-κB signaling pathways and also shows an authentic effect on reducing gastric inflammation.

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