Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi, Alessandro; Giuliani, Massimo

doi:10.3390/vaccines4040041

Cited by 47 publications

(65 citation statements)

References 180 publications

(349 reference statements)

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“…Bone marrow MSCs (BMMSC) can be mobilized from bone marrow to the site of damage under injury and inflammation conditions, responding to the local microenvironment and exerting immunosuppressive and anti‐inflammatory functions . Moreover, MSCs can participate in the formation of tumor microenvironment and interact with cancer cells . The roles of MSCs in cancer have gained extensive attention in recent years.…”

Section: Introductionmentioning

confidence: 99%

UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell-Exosome Promoted Gastric Cancer Progression via Wnt/β-Catenin Pathway

et al. 2017

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The deficiency or mutation of p53 has been linked to several types of cancers. The mesenchymal stem cell (MSC) is an important component in the tumor microenvironment, and exosomes secreted by MSCs can transfer bioactive molecules, including proteins and nucleic acid, to other cells in the tumor microenvironment to influence the progress of a tumor. However, whether the state of p53 in MSCs can impact the bioactive molecule secretion of exosomes to promote cancer progression and the regulatory mechanism remains elusive. Our study aimed to investigate the regulation of ubiquitin protein ligase E3 component n-recognin 2 (UBR2) enriched in exosomes secreted by p53 deficient mouse bone marrow MSC (p53 mBMMSC) in gastric cancer progression in vivo and in vitro. We found that the concentration of exosome was significantly higher in p53 mBMMSC than that in p53 wild-type mBMMSC (p53 mBMMSC). In particular, UBR2 was highly expressed in p53 mBMMSC cells and exosomes. P53 mBMMSC exosomes enriched UBR2 could be internalized into p53 mBMMSC and murine foregastric carcinoma (MFC) cells and induce the overexpression of UBR2 in these cells which elevated cell proliferation, migration, and the expression of stemness-related genes. Mechanistically, the downregulation of UBR2 in p53 mBMMSC exosomes could reverse these actions. Moreover, a majority of Wnt family members, β-catenin, and its downstream genes (CD44, CyclinD1, CyclinD3, and C-myc) were significantly decreased in MFC knockdown UBR2 and β-catenin depletion, an additional depletion of UBR2 had no significant difference in the expression of Nanog, OCT4, Vimentin, and E-cadherin. Taken together, our findings indicated that p53 mBMMSC exosomes could deliver UBR2 to target cells and promote gastric cancer growth and metastasis by regulating Wnt/β-catenin pathway. Stem Cells 2017;35:2267-2279.

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Section: Introductionmentioning

confidence: 99%

UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell-Exosome Promoted Gastric Cancer Progression via Wnt/β-Catenin Pathway

et al. 2017

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“…MSCs potentially support tumor development through immune suppression, epithelial mesenchymal transition, angiogenesis, and serve as cancer stromal cells [1][2][3]. It is verified that bone marrow MSCs is the main source of carcinoma associated fibroblasts in breast cancer microenvironment [3].…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

Xia¹,

Yu²,

Mao³

et al. 2018

Oncotarget

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Exosomes contain many important components including miRNAs for cancerstromal communication. Mesenchymal stromal cells support tumor development, however, the low expression of miRNAs in exosomes and their regulation roles from mesenchymal stromal cells are still unclear. In this study, we hypothesized that mesenchymal stromal cells-derived exosomes promote breast cancer cell glycolysis. Our results showed that mesenchymal stromal cells-derived exosomes promoted cell proliferation and glycolysis of breast cancer cells. Furthermore, sequencing of exosomal RNAs revealed miR-216b-5p, miR-33a-5p and miR-122-5p were lack of expression in exosomes from mesenchymal stromal cells. MiR-216b-5p, miR-33a-5p and miR-122-5p overexpression in breast cancer cells suppressed glycolysis by targeting HK2, LDHA and PKM2 respectively. These results provided valuable insights and mechanism of mesenchymal stromal cells-secreted exosomes on the glycolysis of breast cancer.

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“…Under basal culture conditions, MSCs are known to express myogenic, osteogenic, adipogenic, and immunogenic markers without stimulation or exposure to differentiation media (Drost et al, ; Gunetti et al, ; Karaoz et al, ; Poggi & Giuliani, ). However, because the D‐ECM incorporated into our gelloids is skeletal muscle‐specific, we hypothesized that MSCs would likely favor a myogenic lineage.…”

Section: Discussionmentioning

confidence: 99%

Decellularized extracellular matrix gelloids support mesenchymal stem cell growth and function in vitro

Talovic

Patel

Schwartz

et al. 2019

J Tissue Eng Regen Med

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Volumetric muscle loss (VML) injuries are irrecoverable due to a significant loss of regenerative elements, persistent inflammation, extensive fibrosis, and functional impairment. When used in isolation, previous stem cell and biomaterial‐based therapies have failed to regenerate skeletal muscle at clinically relevant levels. The extracellular matrix (ECM) microenvironment is crucial for the viability, stemness, and differentiation of stem cells. Decellularized‐ECM (D‐ECM) scaffolds are at the forefront of ongoing research to develop a viable therapy for VML. Due to the retention of key ECM components, D‐ECM scaffolds provide an excellent substrate for the adhesion and migration of several cell types. Mesenchymal stem cells (MSCs) possess regenerative and immunomodulatory properties and are currently under investigation in clinical trials for a wide range of medical conditions. However, a major limitation to the use of MSCs in clinical applications is their poor viability at the site of transplantation. In this study, we have fabricated spherical scaffolds composed of gelatin and skeletal muscle D‐ECM for the adhesion and delivery of MSCs to the site of VML injury. These spherical scaffolds termed “gelloids” supported MSC survival, expansion, trophic factor secretion, immunomodulation, and myogenic protein expression in vitro. Future studies would determine the therapeutic efficacy of this approach in a murine model of VML injury.

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Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Cited by 47 publications

References 180 publications

UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell-Exosome Promoted Gastric Cancer Progression via Wnt/β-Catenin Pathway

UBR2 Enriched in p53 Deficient Mouse Bone Marrow Mesenchymal Stem Cell-Exosome Promoted Gastric Cancer Progression via Wnt/β-Catenin Pathway

WITHDRAWN: Lack of miR-216b-5p, miR-33a-5p or miR-122-5p in MSCs exosomes promotes breast cancer glycolysis by targeting HK2, LDHA and PKM2

Decellularized extracellular matrix gelloids support mesenchymal stem cell growth and function in vitro

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