The Effect of Autophagy Induction in Oncolytic Reovirus Replication in Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Shiva Maleki ◽  
Hoorieh Soleimanjahi ◽  
Asghar Abdoli ◽  
Hesam Karimi ◽  
Razieh Sadat Banijamali ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
L929 Cell ◽  
Expression Level ◽  
L929 Cells ◽  
Host Interactions ◽  
Relative Expression Level ◽  
Autophagy Induction ◽  
Reovirus Type ◽  
Reovirus Replication

Background and Aims: Oncolytic reoviruses can infect and kill malignant cells while sparing their normal counterparts. Reoviral infection can induce or activate autophagy, even though metformin can induce autophagy. Identifying and regulating the cellular pathways important for reovirus replication and oncolysis can improve targeted-biological therapies for cancer. Here, the autophagic process was triggered via metformin, and we investigated the effect of autophagy activation on oncolytic reovirus replication in mesenchymal stem cells as primary cells and L929 cell lines. Materials and Methods: Adipose derived mesenchymal stem cells (AD-MSCs) and L929 cells were treated with metformin and reovirus type-3 strain Dearing (T3D). Twenty-four hours after infection, the viability of AD-MSCs and L929 cells were examined by MTT assay. Also, the effect of metformin-induced autophagy in the reovirus replication in these cells was determined by real-time polymerase-chain-reaction. Results: Our results show that treatment with metformin and reovirus reduced the viability of the cells compared to treatment with metformin or reovirus alone in both cells. Also, coadministration of metformin and reovirus significantly decreased the relative expression level of the Beclin-1 gene compared to treatment with metformin in both cells. However, the expression level of the reovirus L3 gene after treatment with metformin and reovirus in L929 cells increased significantly compared to AD-MSCs. Conclusion: Our data suggest that metformin-induced autophagy enhances reoviral replication in AD-MSCs and L929 cells. These findings represent the role of autophagy induction in facilitating reovirus replication and contribute to a better understanding of reovirus-host interactions.

Correlation between cell morphology and aggrecan gene expression level during differentiation from mesenchymal stem cells to chondrocytes

2008 ◽  
Vol 30 (7) ◽  
pp. 1189-1195 ◽  
Author(s):  
Mutsumi Takagi ◽  
Takayuki Kitabayashi ◽  
Satoru Koizumi ◽  
Haruka Hirose ◽  
Shin-ichi Kondo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Morphology ◽  
Gene Expression Level ◽  
Expression Level

scholarly journals Resveratrol Induces the Osteogenic Differentiation via MiR-320c by Targeting Runx2 and Is Involved in the Adipogenic differentiation of BMSCs

2020 ◽  
Author(s):  
Jilong Zou ◽  
Jianyang Du ◽  
Hualei Tu ◽  
Hongjun Chen ◽  
Kai Cong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Target Gene ◽  
Target Genes ◽  
Adipogenic Differentiation ◽  
Expression Level ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Matrix Mineralization

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) are multipotent progenitor cells and have been widely used in clinical therapies due to their multiple pluripotency. Recent publications have found that resveratrol (RSVL) could promote the proliferation and differentiation of mesenchymal stem cells; however, the underlying molecular mechanism of RSVL-induced BMSCs osteogenic differentiation needs to be fully elucidated. The aim of this study was to investigate the function of miRNAs in RSVL-treated BMSCs and its effects on the osteogenic differentiation of BMSCs. Methods BMSCs were cultured and treated with different concentrations of RSVL. After osteogenic differentiation for 20 days, ALP staining was performed to evaluate the ALP activity of BMSCs. And ARS staining was used to detect the matrix mineralization deposition of BMSCs. After adipogenic differentiation for 20 days, adipogenic differentiation was determined by ORO staining for lipid droplets. Quantitative real-time polymerase chain reaction analysis was performed to assess the expression level of target genes. Bioinformatics analysis and luciferase reporter assay was ultilized to examine the relationship between miR-320c and its target gene. Western blot assay was used to analyze the protein expression level of target gene. Results Our results demonstrated that RSVL could promote the osteogenic differentiation and suppressed the adipogenic differentiation of BMSCs in a dose-dependent manner. Besides, a novel regulatory axis containing miR-320c and its target Runx2 was found during the differentiation process of BMSCs under RSVL treatment. Overexpression of miR-320c inhibited the osteogenic differentiation, while knockdown of miR-320c promoted the osteogenic differentiation of BMSCs. In contrast, overexpression of miR-320c accelerated the adipogenic differentiation, while knockdown of miR-320c restrained the adipogenic differentiation of BMSCs. Our results confirm that Runx2 was the directly target of miR-320c in RSVL-promoted osteogenic differentiation of BMSCs. Conclusions The present study revealed that miR-320c might possess the potentials as a novel clinical target for medical intervention to regulate the biological functions of RSVL in BMSCs.

scholarly journals Autophagy induction in the skeletal myogenic differentiation of human tonsil-derived mesenchymal stem cells

2017 ◽  
Vol 39 (4) ◽  
pp. 831-840 ◽  
Author(s):  
Saeyoung Park ◽  
Yoonyoung Choi ◽  
Namhee Jung ◽  
Jieun Kim ◽  
Seiyoon Oh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Myogenic Differentiation ◽  
Human Tonsil ◽  
Autophagy Induction

scholarly journals The Role of CDR1as in Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Lunyu Yang ◽  
Zhang Bin ◽  
Shi Hui ◽  
Li Rong ◽  
Benshuai You ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Expression Level ◽  
Human Umbilical Cord ◽  
Biological Processes ◽  
Promising Tool ◽  
Proliferation And Differentiation ◽  
Cell Induction

Mesenchymal stem cells derived from human umbilical cord (hucMSCs) are considered a promising tool for regenerative medicine. circRNAs as newly discovered noncoding RNAs are involved in multiple biological processes. However, little has been known about the function of circRNAs in the proliferation and differentiation of hucMSCs. In this study, we selected several circRNAs expressed in MSCs from circBase and found that CDR1as expression level was markedly significant. We observed that, compared with that of uninduced hucMSCs, the CDR1as expression level of induced hucMSCs decreased with cell induction differentiation. By using siRNA to knock down CDR1as of hucMSCs, we discovered that proliferation was inhibited but the apoptosis increased. In addition, we found that the expression of stemness transcription factors (STFs) was downregulated after CDR1as knockdown and the adipogenesis and osteogenesis potential of hucMSCs was impaired. Our findings suggest that CDR1as takes a part in maintaining proliferation and differentiation of hucMSCs, providing clues for MSC modification and further for stem cell therapy and tissue regeneration.

scholarly journals Human amnion-derived mesenchymal stem cells improved the reproductive function of age-related diminished ovarian reserve in mice through Ampk/FoxO3a signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Hanwen Liu ◽  
Chunyan Jiang ◽  
Boya La ◽  
Meng Cao ◽  
Song Ning ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Ovarian Reserve ◽  
Stromal Cells ◽  
Ovarian Function ◽  
Expression Level ◽  
Human Amnion ◽  
Age Related ◽  
Old Mice

Abstract Background Age-related diminished ovarian reserve (AR-DOR) reduced the quality of oocytes, resulting in decreased female fertility. Aging is tightly related to abnormal distribution and function of mitochondria, while mitophagy is a major process to maintain normal quality and quantity of mitochondria in cells, especially in oocytes which containing a large number of mitochondria to meet the demand of energy production during oocyte maturation and subsequent embryonic development. Ampk/FoxO3a signaling is crucial in the regulation of mitophagy. It is reported mesenchymal stem cells (MSCs) can improve ovarian function. Here we aim to explore if human amnion-derived mesenchymal stem cells (hAMSCs) are effective in improving ovarian function in AR-DOR mice and whether Ampk/FoxO3a signaling is involved. Methods The AR-DOR model mice were established by 32-week-old mice with 3–8 litters, significantly low serum sex hormone levels and follicle counts. The old mice were divided into 5 treatment groups: normal saline (NS, control), 1% human serum albumin (HSA, resolver), low dose (LD, 5.0 × 106cells/kg), middle dose (MD, 7.5 × 106cells/kg), and high dose (HD, 10.0 × 106cells/kg). The prepared hAMSCs were injected through tail vein. Serum sex hormone level, follicle counts, fertilization rate, gestation rate, little size, apoptosis of granulosa and stromal cells, expression level of Sod2, Ampk, and ratio of phosphorylated FoxO3a to total FoxO3a in ovaries were examined. Results Our results show that after hAMSC transplantation, the ovarian function in AR-DOR mice was significantly improved, meanwhile the apoptosis of granulosa and stromal cells in the ovaries was significantly repressed, the expression level of Ampk and the ratio of phosphorylated FoxO3a to total FoxO3a both were significantly increased, meanwhile increased Sod2 expression was also observed. Conclusion Our results demonstrate hAMSC transplantation via tail-injection can improve ovarian function of AR-DOR mice through Ampk/FoxO3a signaling pathway.

scholarly journals From the Cover: Autophagy Induction Contributes to Cadmium Toxicity in Mesenchymal Stem Cells via AMPK/FOXO3a/BECN1 Signaling

2016 ◽  
Vol 154 (1) ◽  
pp. 101-114 ◽  
Author(s):  
Min Yang ◽  
Huifeng Pi ◽  
Min Li ◽  
Shangcheng Xu ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cadmium Toxicity ◽  
Autophagy Induction

scholarly journals The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1

2020 ◽  
Vol 18 ◽  
pp. 205873922093456
Author(s):  
Hyun Seop Cho ◽  
Ha Nee Jang ◽  
Myeong Hee Jung ◽  
Si Jung Jang ◽  
Sang-Ho Jeong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Expression Level ◽  
Heme Oxygenase 1 ◽  
Sprague Dawley ◽  
Migration Ability ◽  
Induced Apoptosis

The therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic efficacy of Ad-MSCs is dependent on their expression level of HO-1. The viability and migration ability of cisplatin-treated human renal proximal tubular epithelial cells were assessed. Sprague–Dawley rats were divided into control, cisplatin (10 mg/kg), and cisplatin plus Ad MSCs (with high and low HO-1 expression) groups. The HO-1 expression level in hAd-MSCs increased with increasing passage number, peaking at passage 4 and decreasing thereafter. The viability and migratory ability of hAd-MSCs with high HO-1 expression were greater than those of hAd-MSCs with low HO-1 expression. Renal tubular toxicity in cisplatin-treated rats was ameliorated by administration of hAd-MSCs with high HO-1 expression, although the levels of blood urea nitrogen and serum creatinine did not differ according to the level of HO-1 expression. The magnitude of reactive oxygen species induced DNA damage was lower in hAd-MSCs with high HO-1 expression than in those with low HO-1 expression. Administration of hAd-MSCs significantly suppressed cisplatin induced apoptosis. Also, hAd-MSCs with high HO-1 expression were more resistant to cisplatin-induced apoptosis than were those with low HO-1 expression. hAd MSCs with high HO-1 expression have therapeutic potential for cisplatin induced nephrotoxicity, based on our in vitro and in vivo results. These findings will facilitate the development of novel therapeutic strategies for cisplatin-induced AKI.

Sign in / Sign up

Export Citation Format

Share Document