scholarly journals Bidirectional and Opposite Effects of Naïve Mesenchymal Stem Cells Ontumor Growth and Progression

2019 ◽  
Vol 9 (4) ◽  
pp. 539-558 ◽  
Author(s):  
Faramarz Rahmatizadeh ◽  
Shiva Gholizadeh-Ghaleh Aziz ◽  
Khodadad Khodadadi ◽  
Maryam Lale Ataei ◽  
Esmaeil Ebrahimie ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Cells ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Tumor Stroma ◽  
Cell Types ◽  
Great Promise ◽  
Tumor Tissues ◽  
Essential Components

Cancer has long been considered as a heterogeneous population of uncontrolled proliferation ofdifferent transformed cell types. The recent findings concerning tumorigeneses have highlightedthe fact that tumors can progress through tight relationships among tumor cells, cellular, andnon-cellular components which are present within tumor tissues. In recent years, studies haveshown that mesenchymal stem cells (MSCs) are essential components of non-tumor cells withinthe tumor tissues that can strongly affect tumor development. Several forms of MSCs have beenidentified within tumor stroma. Naïve (innate) mesenchymal stem cells (N-MSCs) derived fromdifferent sources are mostly recruited into the tumor stroma. N-MSCs exert dual and divergenteffects on tumor growth through different conditions and factors such as toll-like receptorpriming (TLR-priming), which is the primary underlying causes of opposite effects. Moreover,MSCs also have the contrary effects by various molecular mechanisms relying on direct cellto-cell connections and indirect communications through the autocrine, paracrine routes, andtumor microenvironment (TME).Overall, cell-based therapies will hold great promise to provide novel anticancer treatments.However, the application of intact MSCs in cancer treatment can theoretically cause adverseclinical outcomes. It is essential that to extensively analysis the effective factors and conditionsin which underlying mechanisms are adopted by MSCs when encounter with cancer.The aim is to review the cellular and molecular mechanisms underlying the dual effects ofMSCs followed by the importance of polarization of MSCs through priming of TLRs.<br />

Mesenchymal Stem Cells and Cancer Stem Cells: An Overview of Tumor-Mesenchymal Stem Cell Interaction for therapeutic interventions

2021 ◽  
Vol 22 ◽  
Author(s):  
Soheila Montazersaheb ◽  
Ezzatollah Fathi ◽  
Ayoub Mamandi ◽  
Raheleh Farahzadi ◽  
Hamid Reza Heidari
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Stem Cells ◽  
Tumor Cells ◽  
Cell Types ◽  
Cell Interaction ◽  
Therapeutic Interventions ◽  
Tumorigenic Potential ◽  
Different Types

: Tumors are made up of different types of cancer cells that contribute to tumor heterogeneity. Among these cells, cancer stem cells (CSCs) have a significant role in the onset of cancer and development. Like other stem cells, CSCs are characterized by the capacity for differentiation and self-renewal. A specific population of CSCs is constituted by mesenchymal stem cells (MSCs) that differentiate into mesoderm-specific cells. The pro-or anti-tumorigenic potential of MSCs on the proliferation and development of tumor cells has been reported as contradictory results. Also, tumor progression is specified by the corresponding tumor cells like the tumor microenvironment. The tumor microenvironment consists of a network of reciprocal cell types such as endothelial cells, immune cells, MSCs, and fibroblasts as well as growth factors, chemokines, and cytokines. In this review, recent findings related to the tumor microenvironment and associated cell populations, homing of MSCs to tumor sites, and interaction of MSCs with tumor cells will be discussed.

scholarly journals The Winding Road of Cardiac Regeneration—Stem Cell Omics in the Spotlight

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 255 ◽  
Author(s):  
Miruna Mihaela Micheu ◽  
Alina Ioana Scarlatescu ◽  
Alexandru Scafa-Udriste ◽  
Maria Dorobantu
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Cell Fate ◽  
Cell Biology ◽  
Molecular Mechanisms ◽  
Unmet Need ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Great Promise ◽  
Omics Data

Despite significant progress in treating ischemic cardiac disease and succeeding heart failure, there is still an unmet need to develop effective therapeutic strategies given the persistent high-mortality rate. Advances in stem cell biology hold great promise for regenerative medicine, particularly for cardiac regeneration. Various cell types have been used both in preclinical and clinical studies to repair the injured heart, either directly or indirectly. Transplanted cells may act in an autocrine and/or paracrine manner to improve the myocyte survival and migration of remote and/or resident stem cells to the site of injury. Still, the molecular mechanisms regulating cardiac protection and repair are poorly understood. Stem cell fate is directed by multifaceted interactions between genetic, epigenetic, transcriptional, and post-transcriptional mechanisms. Decoding stem cells’ “panomic” data would provide a comprehensive picture of the underlying mechanisms, resulting in patient-tailored therapy. This review offers a critical analysis of omics data in relation to stem cell survival and differentiation. Additionally, the emerging role of stem cell-derived exosomes as “cell-free” therapy is debated. Last but not least, we discuss the challenges to retrieve and analyze the huge amount of publicly available omics data.

scholarly journals More to Explore; The Mesenchymal Stem Cells (MSCs) Major Tissue Sources, Known Surface Markers, and Its Immunomodulation properties

2021 ◽  
pp. 85-97
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Immune Modulation ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Surface Markers ◽  
Differentiation Potential ◽  
Disease Therapy ◽  
Multipotent Progenitor Cells ◽  
Mesodermal Origin

Mesenchymal stem cells (MSCs) are currently available for a range of applications and have become a good material for regenerative medicine, tissue engineering, and disease therapy. MSCs are self-renewing, multipotent progenitor cells with multilineage potential to differentiate into cell types of mesodermal origin, such as adipocytes, osteocytes, and chondrocytes, and exert potent immunosuppressive potentials. In the present review, we highlight the currently reported variations in the differentiation potential of MSCs from different tissue sources, the minimal criteria to define MSCs from various tissue environments, and provide a detailed description of MSCs surface markers. Furthermore, MSC's immunomodulatory features secrete cytokines and immune receptors which regulate the microenvironment in the host tissue also revisits in detail. We propose that there are likely more sources of MSCs waiting to be discovered. We need to Standardize MSCs characterization by selecting markers for isolation, cellular and molecular mechanisms involved in MSC-mediated immune modulation, and other functionalities of MSCs should be characterized prior to use in clinical applications.

scholarly journals SIRT1 Inhibition Affects Angiogenic Properties of Human MSCs

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Botti Chiara ◽  
Caiafa Ilaria ◽  
Coppola Antonietta ◽  
Cuomo Francesca ◽  
Miceli Marco ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Therapeutic Angiogenesis ◽  
Induced Response ◽  
Human Mscs ◽  
Hypoxic Conditions ◽  
And Migration

Human mesenchymal stem cells (hMSCs) are attractive for clinical and experimental purposes due to their capability of self-renewal and of differentiating into several cell types. Autologous hMSCs transplantation has been proven to induce therapeutic angiogenesis in ischemic disorders. However, the molecular mechanisms underlying these effects remain unclear. A recent report has connected MSCs multipotency to sirtuin families, showing that SIRT1 can regulate MSCs function. Furthermore, SIRT1 is a critical modulator of endothelial angiogenic functions. Here, we described the generation of an immortalized human mesenchymal bone marrow-derived cell line and we investigated the angiogenic phenotype of our cellular model by inhibiting SIRT1 by both the genetic and pharmacological level. We first assessed the expression of SIRT1 in hMSCs under basal and hypoxic conditions at both RNA and protein level. Inhibition of SIRT1 by sirtinol, a cell-permeable inhibitor, or by specific sh-RNA resulted in an increase of premature-senescence phenotype, a reduction of proliferation rate with increased apoptosis. Furthermore, we observed a consistent reduction of tubule-like formation and migration and we found that SIRT1 inhibition reduced the hypoxia induced accumulation of HIF-1α protein and its transcriptional activity in hMSCs. Our findings identify SIRT1 as regulator of hypoxia-induced response in hMSCs and may contribute to the development of new therapeutic strategies to improve regenerative properties of mesenchymal stem cells in ischemic disorders through SIRT1 modulation.

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.

scholarly journals Mesenchymal stem cells carry and transport clusters of cancer cells

2021 ◽  
Author(s):  
Jana Zarubova ◽  
Mohammad Mahdi Hasani-Sadrabadi ◽  
Sam CP Norris ◽  
Andrea M Kasko ◽  
Song Li
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Migration ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cancer Cell ◽  
Cell Types ◽  
Cell Clusters ◽  
Different Cell Types

AbstractCell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of collective cell migration phenomenon and the involvement of different cell types during this process is needed. Here, we utilize a micropatterned surface composed of a thousand of low-adhesive microwells to screen motility of spheroids containing different cell types by analyzing their ability to move from the bottom to the top of the microwells. Mesenchymal stem cells (MSCs) spheroid migration was efficient in contrast to cancer cell only spheroids. In spheroids with both cell types mixed together, MSCs were able to carry the low-motile cancer cells during migration. As the percentage of MSCs increased in the spheroids, more migrating spheroids were detected. Extracellular vesicles secreted by MSCs also contributed to the pro-migratory effect exerted by MSCs. However, the transport of cancer cells was more efficient when MSCs were physically present in the cluster. Similar results were obtained when cell clusters were encapsulated within a micropatterned hydrogel, where collective migration was guided by micropatterned matrix stiffness. These results suggest that stromal cells facilitate the migration of cancer cell clusters, which is contrary to the general belief that malignant cells metastasize independently.SignificanceDuring metastasis, tumor cells may migrate as a cluster, which exhibit higher metastatic capacity compared to single cells. However, whether and how non-cancer cells contained in tumor cluster regulate it’s migration is not clear. Here, we utilize two unique approaches to study collective tumor cell migration in vitro: first, in low-adhesive microwells and second, in micropatterned hydrogels to analyze migration in 3D microenvironment. Our results indicate that MSCs in tumor cell clusters could play an important role in the dissemination of cancer cells by actively transporting low-motile cancer cells. In addition, MSC-released paracrine factors also increase the motility of tumor cells. These findings reveal a new mechanism of cancer cell migration and may lead to new approaches to suppress metastases.

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.

scholarly journals Extracellular Microvesicles (MV’s) Isolated from 5-Azacytidine-and-Resveratrol-Treated Cells Improve Viability and Ameliorate Endoplasmic Reticulum Stress in Metabolic Syndrome Derived Mesenchymal Stem Cells

2020 ◽  
Vol 16 (6) ◽  
pp. 1343-1355
Author(s):  
C Weiss ◽  
K Kornicka-Grabowska ◽  
M Mularczyk ◽  
N Siwinska ◽  
K Marycz
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cells ◽  
Endoplasmic Reticulum ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Biological Effects ◽  
Cell Types ◽  
Wide Range ◽  
Proper Functions

AbstractExtracellular vesicles (EVs), a spherical membrane fragments including exosomes, are released from several cell types, including mesenchymal stromal cells (MSCs), constitutively or under stimulation. As MVs cargo include DNA, RNA, miRNA, lipids and proteins their have gain special attention in the field of regenerative medicine. Depending on the type of transferred molecules, MVs may exert wide range of biological effects in recipient cells including pro-inflammatory and anti-apoptotic action. In presented paper, we isolated MVs form adipose derived mesenchymal stem cells (ASC) which underwent stimulation with 5-azacytydine and resveratrol (AZA/RES) in order to improve their therapeutic potential. Then, isolated MVs were applied to ASC with impaired cytophysiological properties, isolated from equine metabolic syndrome diagnosed animals. Using RT-PCR, immunofluorescence, ELISA, confocal microscopy and western blot, we have evaluated the effects of MVs on recipient cells. We have found, that MVs derived from AZA/RES treated ASC ameliorates apoptosis, senescence and endoplasmic reticulum (ER) stress in deteriorated cells, restoring their proper functions. The work indicates, that cells treated with AZA/RES through their paracrine action can rejuvenate recipient cells. However, further research needs to be performed in order to fully understand the molecular mechanisms of these bioactive factors action.

scholarly journals A Bifunctional Molecule with Lectin and Protease Inhibitor Activities Isolated from Crataeva tapia Bark Significantly Affects Cocultures of Mesenchymal Stem Cells and Glioblastoma Cells

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2109 ◽  
Author(s):  
Camila Ramalho Bonturi ◽  
Mariana Cristina Cabral Silva ◽  
Helena Motaln ◽  
Bruno Ramos Salu ◽  
Rodrigo da Silva Ferreira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Cells ◽  
Tumor Stroma ◽  
Tree Bark ◽  
Cell Contact ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Stromal Microenvironment

Currently available drugs for treatment of glioblastoma, the most aggressive brain tumor, remain inefficient, thus a plethora of natural compounds have already been shown to have antimalignant effects. However, these have not been tested for their impact on tumor cells in their microenvironment-simulated cell models, e.g., mesenchymal stem cells in coculture with glioblastoma cell U87 (GB). Mesenchymal stem cells (MSC) chemotactically infiltrate the glioblastoma microenvironment. Our previous studies have shown that bone-marrow derived MSCs impair U87 growth and invasion via paracrine and cell–cell contact-mediated cross-talk. Here, we report on a plant-derived protein, obtained from Crataeva tapia tree Bark Lectin (CrataBL), having protease inhibitory/lectin activities, and demonstrate its effects on glioblastoma cells U87 alone and their cocultures with MSCs. CrataBL inhibited U87 cell invasion and adhesion. Using a simplified model of the stromal microenvironment, i.e., GB/MSC direct cocultures, we demonstrated that CrataBL, when added in increased concentrations, caused cell cycle arrest and decreased cocultured cells’ viability and proliferation, but not invasion. The cocultured cells’ phenotypes were affected by CrataBL via a variety of secreted immunomodulatory cytokines, i.e., G-CSF, GM-CSF, IL-6, IL-8, and VEGF. We hypothesize that CrataBL plays a role by boosting the modulatory effects of MSCs on these glioblastoma cell lines and thus the effects of this and other natural lectins and/or inhibitors would certainly be different in the tumor microenvironment compared to tumor cells alone. We have provided clear evidence that it makes much more sense testing these potential therapeutic adjuvants in cocultures, mimicking heterogeneous tumor–stroma interactions with cancer cells in vivo. As such, CrataBL is suggested as a new candidate to approach adjuvant treatment of this deadly tumor.

scholarly journals Concentration-dependent inhibition of angiogenesis by mesenchymal stem cells

Blood ◽  
2009 ◽  
Vol 113 (18) ◽  
pp. 4197-4205 ◽  
Author(s):  
Keishi Otsu ◽  
Shonit Das ◽  
Sandra D. Houser ◽  
Sadiqa K. Quadri ◽  
Sunita Bhattacharya ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Tumor Model ◽  
Cell Types ◽  
Host Cells ◽  
Angiogenesis Assay ◽  
Junctional Communication ◽  
Induced Apoptosis

Abstract Mesenchymal stem cells (MSCs), which potentially transdifferentiate into multiple cell types, are increasingly reported to be beneficial in models of organ system injury. However, the molecular mechanisms underlying interactions between MSCs and host cells, in particular endothelial cells (ECs), remain unclear. We show here in a matrigel angiogenesis assay that MSCs are capable of inhibiting capillary growth. After addition of MSCs to EC-derived capillaries in matrigel at EC:MSC ratio of 1:1, MSCs migrated toward the capillaries, intercalated between ECs, established Cx43-based intercellular gap junctional communication (GJC) with ECs, and increased production of reactive oxygen species (ROS). These events led to EC apoptosis and capillary degeneration. In an in vivo tumor model, direct MSC inoculation into subcutaneous melanomas induced apoptosis and abrogated tumor growth. Thus, our findings show for the first time that at high numbers, MSCs are potentially cytotoxic and that when injected locally in tumor tissue they might be effective antiangiogenesis agents suitable for cancer therapy.

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