scholarly journals Mesenchymal stem cells induce epithelial proliferation within the inflamed stomach

2014 ◽  
Vol 306 (12) ◽  
pp. G1075-G1088 ◽  
Author(s):  
Jessica M. Donnelly ◽  
Amy Engevik ◽  
Rui Feng ◽  
Chang Xiao ◽  
Gregory P. Boivin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Hedgehog Signaling ◽  
Fluorescent Protein ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Gastric Epithelium ◽  
Wild Type

Bone marrow-derived mesenchymal stem cells (MSCs) sustain cancer cells by creating a microenvironment favorable for tumor growth. In particular, MSCs have been implicated in gastric cancer development. There is extensive evidence suggesting that Hedgehog signaling regulates tumor growth. However, very little is known regarding the precise roles of Hedgehog signaling and MSCs in tumor development within the stomach. The current study tests that hypothesis that Sonic Hedgehog (Shh), secreted from MSCs, provides a proliferative stimulus for the gastric epithelium in the presence of inflammation. Red fluorescent protein-expressing MSCs transformed in vitro (stMSCs) were transduced with lentiviral constructs containing a vector control (stMSCvect) or short hairpin RNA (shRNA) targeting the Shh gene (stMSCShhKO). Gastric submucosal transplantation of wild-type MSCs (wtMSCs), wild-type MSCs overexpressing Shh (wtMSCShh), stMSCvect, or stMSCShhKO cells in C57BL/6 control (BL/6) or gastrin-deficient (GKO) mice was performed and mice analyzed 30 and 60 days posttransplantation. Compared with BL/6 mice transplanted with wtMSCShh and stMSCvect cells, inflamed GKO mice developed aggressive gastric tumors. Tumor development was not observed in mouse stomachs transplanted with wtMSC or stMSCShhKO cells. Compared with stMSCShhKO-transplanted mice, within the inflamed GKO mouse stomach, Shh-expressing stMSCvect- and wtMSCShh-induced proliferation of CD44-positive cells. CD44-positive cells clustered in gland-like structures within the tumor stroma and were positive for Patched (Ptch) expression. We conclude that Shh, secreted from MSCs, provides a proliferative stimulus for the gastric epithelium that is associated with tumor development, a response that is sustained by chronic inflammation.

Decidua mesenchymal stem cells migrated toward mammary tumors in vitro and in vivo affecting tumor growth and tumor development

2012 ◽  
Vol 20 (1) ◽  
pp. 8-16 ◽  
Author(s):  
I Vegh ◽  
M Grau ◽  
M Gracia ◽  
J Grande ◽  
P de la Torre ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Tumor Development ◽  
Mammary Tumors

scholarly journals Mesenchymal stem cells express serine protease inhibitor to evade the host immune response

Blood ◽  
2011 ◽  
Vol 117 (4) ◽  
pp. 1176-1183 ◽  
Author(s):  
Najib El Haddad ◽  
Dean Heathcote ◽  
Robert Moore ◽  
Sunmi Yang ◽  
Jamil Azzi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Cell ◽  
Protease Inhibitor ◽  
Serine Protease ◽  
Serine Protease Inhibitor ◽  
Cytotoxic T Cell ◽  
Wild Type

Abstract Clinical trials using mesenchymal stem cells (MSCs) have been initiated worldwide. An improved understanding of the mechanisms by which allogeneic MSCs evade host immune responses is paramount to regulating their survival after administration. This study has focused on the novel role of serine protease inhibitor (SPI) in the escape of MSCs from host immunosurveillance through the inhibition of granzyme B (GrB). Our data indicate bone marrow–derived murine MSCs express SPI6 constitutively. MSCs from mice deficient for SPI6 (SPI6−/−) exhibited a 4-fold higher death rate by primed allogeneic cytotoxic T cells than did wild-type MSCs. A GrB inhibitor rescued SPI6−/− MSCs from cytotoxic T-cell killing. Transduction of wild-type MSCs with MigR1-SPI6 also protected MSCs from cytotoxic T cell–mediated death in vitro. In addition, SPI6−/− MSCs displayed a shorter lifespan than wild-type MSCs when injected into an allogeneic host. We conclude that SPI6 protects MSCs from GrB-mediated killing and plays a pivotal role in their survival in vivo. Our data could serve as a basis for future SPI-based strategies to regulate the survival and function of MSCs after administration and to enhance the efficacy of MSC-based therapy for diseases.

scholarly journals Mesenchymal stem cells promote glioma neovascularization in vivo by fusing with cancer stem cells

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Chao Sun ◽  
Xingliang Dai ◽  
Dongliang Zhao ◽  
Haiyang Wang ◽  
Xiaoci Rong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Tumor Growth ◽  
Glioma Cells ◽  
Stem Cell Markers ◽  
Xenograft Tumor ◽  
Angiogenic Effect

Abstract Background and objective Tumor angiogenesis is vital for tumor growth. Recent evidence indicated that bone marrow-derived mesenchymal stem cells (BMSCs) can migrate to tumor sites and exert critical effects on tumor growth through direct and/or indirect interactions with tumor cells. However, the effect of BMSCs on tumor neovascularization has not been fully elucidated. This study aimed to investigate whether fusion cells from glioma stem cells and BMSCs participated in angiogenesis. Methods SU3-RFP cells were injected into the right caudate nucleus of NC-C57Bl/6 J-GFP nude mice, and the RFP+/GFP+ cells were isolated and named fusion cells. The angiogenic effects of SU3-RFP, BMSCs and fusion cells were compared in vivo and in vitro. Results Fusion cells showed elevated levels of CD31, CD34 and VE-Cadherin (markers of VEC) as compared to SU3-RFP and BMSCs. The MVD-CD31 in RFP+/GFP+ cell xenograft tumor was significantly greater as compared to that in SU3-RFP xenograft tumor. In addition, the expression of CD133 and stem cell markers Nanog, Oct4 and Sox2 were increased in fusion cells as compared to the parental cells. Fusion cells exhibited enhanced angiogenic effect as compared to parental glioma cells in vivo and in vitro, which may be related to their stem cell properties. Conclusion Fusion cells exhibited enhanced angiogenic effect as compared to parental glioma cells in vivo and in vitro, which may be related to their stem cell properties. Hence, cell fusion may contribute to glioma angiogenesis.

scholarly journals Targeted knock-in mice expressing the oxidase-fixed form of xanthine oxidoreductase favor tumor growth

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Teruo Kusano ◽  
Driss Ehirchiou ◽  
Tomohiro Matsumura ◽  
Veronique Chobaz ◽  
Sonia Nasi ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Immune Surveillance ◽  
Tumor Development ◽  
Cancer Growth ◽  
Xanthine Oxidoreductase ◽  
Oxygen Species ◽  
Wild Type ◽  
Macrophage Depletion

Abstract Xanthine oxidoreductase has been implicated in cancer. Nonetheless, the role played by its two convertible forms, xanthine dehydrogenase (XDH) and oxidase (XO) during tumorigenesis is not understood. Here we produce XDH-stable and XO-locked knock-in (ki) mice to address this question. After tumor transfer, XO ki mice show strongly increased tumor growth compared to wild type (WT) and XDH ki mice. Hematopoietic XO expression is responsible for this effect. After macrophage depletion, tumor growth is reduced. Adoptive transfer of XO-ki macrophages in WT mice increases tumor growth. In vitro, XO ki macrophages produce higher levels of reactive oxygen species (ROS) responsible for the increased Tregs observed in the tumors. Blocking ROS in vivo slows down tumor growth. Collectively, these results indicate that the balance of XO/XDH plays an important role in immune surveillance of tumor development. Strategies that inhibit the XO form specifically may be valuable in controlling cancer growth.

scholarly journals Stem cell antigen/Ly6a protects against bladder fibrosis in mice

2019 ◽  
Vol 317 (6) ◽  
pp. F1503-F1512 ◽  
Author(s):  
Nicholas M. Tassone ◽  
Belinda Li ◽  
Mehul S. Patel ◽  
Megan Y. Devine ◽  
Paula R. Firmiss ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Outlet Obstruction ◽  
Specific Protein ◽  
Male Mice ◽  
Wild Type ◽  
Cell Antigen ◽  
Steady State Levels

We have defined a population of stem cell antigen (Sca)-1+/CD34+/lin− mesenchymal stem cells in the mouse urinary bladder. These cells are reduced after partial bladder outlet obstruction (PO). To test the role of Sca-1 expressed by these cells, we analyzed bladders from Sca-1 knockout (KO) mice in both uninjured male mice and male mice subjected to PO. We found that loss of Sca-1 alone had little effect on bladder development or function but reduced the total number of mesenchymal stem cells by 30%. After PO, bladders from Sca-1-null KO male mice were larger, with more collagen and less muscle, than obstructed wild-type mice. Steady-state levels of caldesmon were significantly reduced and levels of fibroblast-specific protein 1 were significantly increased in Sca-1 KO mice compared with wild-type mice after PO. In investigating the effects of PO on cell proliferation, we found that loss of Sca-1 changed the timing of cell division in CD34+/lin−, collagen-producing, and smooth muscle cells. PO in combination with loss of Sca-1 drastically reduced the ability of CD34+/lin− cells to form colonies in vitro. Our findings therefore support the hypothesis that Sca-1 protects the bladder from fibrotic remodeling after obstruction, in part by influencing the proliferation of cells responding to the injury.

Exosomes derived from miR-34a-overexpressing mesenchymal stem cells inhibit in vitro tumor growth: A new approach for drug delivery

Life Sciences ◽  
2021 ◽  
Vol 266 ◽  
pp. 118871
Author(s):  
Faezeh Vakhshiteh ◽  
Soheila Rahmani ◽  
Seyed Nasser Ostad ◽  
Zahra Madjd ◽  
Rassoul Dinarvand ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
New Approach

Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals

Blood ◽  
2003 ◽  
Vol 102 (10) ◽  
pp. 3837-3844 ◽  
Author(s):  
Farida Djouad ◽  
Pascale Plence ◽  
Claire Bony ◽  
Philippe Tropel ◽  
Florence Apparailly ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Side Effects ◽  
Tumor Growth ◽  
Tumor Model ◽  
Bone Morphogenetic Protein 2 ◽  
Melanoma Tumor ◽  
Immunocompetent Mice

Abstract Mesenchymal stem cells (MSCs) are largely studied for their potential clinical use. Recently, they have gained further interest after demonstration of an immunosuppressive role. In this study, we investigated whether in vivo injection of MSCs could display side effects related to systemic immunosuppression favoring tumor growth. We first showed in vitro that the murine C3H10T1/2 (C3) MSC line and primary MSCs exhibit immunosuppressive properties in mixed lymphocyte reaction. We demonstrated that this effect is mediated by soluble factors, secreted only on “activation” of MSCs in the presence of splenocytes. Moreover, the immunosuppression is mediated by CD8+ regulatory cells responsible for the inhibition of allogeneic lymphocyte proliferation. We then demonstrated that the C3 MSCs expressing the human bone morphogenetic protein 2 (hBMP-2) differentiation factor were not rejected when implanted in various allogeneic immunocompetent mice and were still able to differentiate into bone. Importantly, using a murine melanoma tumor model, we showed that the subcutaneous injection of B16 melanoma cells led to tumor growth in allogeneic recipients only when MSCs were coinjected. Although the potential side effects of immunosuppression induced by MSCs have to be considered in further clinical studies, the usefulness of MSCs for various therapeutic applications still remains of great interest. (Blood. 2003;102:3837-3844)

scholarly journals Edition of Prostaglandin E2 Receptors EP2 and EP4 by CRISPR/Cas9 Technology in Equine Adipose Mesenchymal Stem Cells

Animals ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 1078
Author(s):  
Ana Carolina Furlanetto Mançanares ◽  
Joel Cabezas ◽  
José Manríquez ◽  
Vanessa Cristina de Oliveira ◽  
Yat Sen Wong Alvaro ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Prostaglandin E2 ◽  
Sanger Sequencing ◽  
Surface Markers ◽  
Wild Type ◽  
Migration Ability ◽  
Knock Out ◽  
Directed Mutation

In mesenchymal stem cells (MSCs), it has been reported that prostaglandin E2 (PGE2) stimulation of EP2 and EP4 receptors triggers processes such as migration, self-renewal, survival, and proliferation, and their activation is involved in homing. The aim of this work was to establish a genetically modified adipose (aMSC) model in which receptor genes EP2 and EP4 were edited separately using the CRISPR/Cas9 system. After edition, the genes were evaluated as to if the expression of MSC surface markers was affected, as well as the migration capacity in vitro of the generated cells. Adipose MSCs were obtained from Chilean breed horses and cultured in DMEM High Glucose with 10% fetal bovine serum (FBS). sgRNA were cloned into a linearized LentiCRISPRv2GFP vector and transfected into HEK293FT cells for producing viral particles that were used to transduce aMSCs. GFP-expressing cells were separated by sorting to obtain individual clones. Genomic DNA was amplified, and the site-directed mutation frequency was assessed by T7E1, followed by Sanger sequencing. We selected 11 clones of EP2 and 10 clones of EP4, and by Sanger sequencing we confirmed 1 clone knock-out to aMSC/EP2 and one heterozygous mutant clone of aMSC/EP4. Both edited cells had decreased expression of EP2 and EP4 receptors when compared to the wild type, and the edition of EP2 and EP4 did not affect the expression of MSC surface markers, showing the same pattern in filling the scratch. We can conclude that the edition of these receptors in aMSCs does not affect their surface marker phenotype and migration ability when compared to wild-type cells.

scholarly journals Primary Cilia as a Biomarker in Mesenchymal Stem Cells Senescence: Influencing Osteoblastic Differentiation Potency Associated with Hedgehog Signaling Regulation

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Su Fu ◽  
Chunlin Zhang ◽  
Xu Yan ◽  
Dongzhe Li ◽  
Yongkui Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hedgehog Signaling ◽  
Primary Cilia ◽  
Osteoblastic Differentiation ◽  
Bone Lesions ◽  
Mediating Role ◽  
Cell Doubling Time ◽  
Autologous Mesenchymal Stem Cells

Bone tissue engineering-based therapy for bone lesions requires the expansion of seeding cells, such as autologous mesenchymal stem cells (MSCs). A major obstacle to this process is the loss of the phenotype and differentiation capacity of MSCs subjected to passage. Recent studies have suggested that primary cilia, primordial organelles that transduce multiple signals, particularly hedgehog signals, play a role in senescence. Therefore, we explored the relationships among senescence, primary cilia, and hedgehog signaling in MSCs. Ageing of MSCs by expansion in vitro was accompanied by increased cell doubling time. The osteogenic capacity of aged MSCs at passage 4 was compromised compared to that of primary cells. P4 MSCs exhibited reductions in the frequency and length of primary cilia associated with decreased intensity of Arl13b staining on cilia. Senescence also resulted in downregulation of the expression of hedgehog components and CDKN2A. Suppression of ciliogenesis reduced the gene expression of both Gli1, a key molecule in the hedgehog signaling pathway and ALP, a marker of osteoblastic differentiation. This study demonstrated that the senescence of MSCs induced the loss of osteoblastic differentiation potency and inactivated hedgehog signaling associated with attenuated ciliogenesis, indicating that primary cilia play a mediating role in and are biomarkers of MSC senescence; thus, future antisenescence strategies involving manipulation of primary cilia could be developed.

scholarly journals Mesenchymal stem cells in cancer progression and anticancer therapeutic resistance

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Xiuyun Xuan ◽  
Chunxia Tian ◽  
Mengjie Zhao ◽  
Yanhong Sun ◽  
Changzheng Huang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cancer Cell ◽  
Cancer Progression ◽  
Tumor Development ◽  
Distinct Type ◽  
Tumor Stroma ◽  
Therapeutic Resistance ◽  
Cancer Cell Proliferation ◽  
Cancer Cell Growth

AbstractIncreasing evidence indicates that the tumor microenvironment appears to play an increasingly important role in cancer progression and therapeutic resistance. Several types of cells within the tumor stroma had distinct impacts on cancer progression, either promoting or inhibiting cancer cell growth. Mesenchymal stem cells (MSCs) are a distinct type of cells that is linked to tumor development. MSCs are recognized for homing to tumor locations and promoting or inhibiting cancer cell proliferation, angiogenesis and metastasis. Moreover, emerging studies suggests that MSCs are also involved in therapeutic resistance. In this review, we analyzed the existing researches and elaborate on the functions of MSCs in cancer progression and anticancer therapeutic resistance, demonstrating that MSCs may be a viable cancer therapeutic target.

Sign in / Sign up

Export Citation Format

Share Document