Resident and bone marrow-derived mesenchymal stem cells in head and neck squamous cell carcinoma

Boeck, Astrid De; Narine, Kishan; Neve, Wilfried De; Mareel, Marcus; Bracke, Marc; Wever, Olivier De

doi:10.1016/j.oraloncology.2010.01.016

Cited by 49 publications

(36 citation statements)

References 103 publications

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“…The literature on tumor tropism, pro-, and antitumorigenicity of MSCs [46,47] is highly controversial. In some studies, MSCs have been reported to promote tumor proliferation, angiogenesis, epithelial-mesenchymal transition, as well as metastasis [46,47], whereas other studies have shown the tumor suppressive effect of MSCs in different tumor models [46]. The unique tumor tropism of MSCs renders them a unique delivery vehicle for antitumor agents [48].…”

Section: Discussionmentioning

confidence: 99%

Three-Dimensional Spheroid Culture of Human Gingiva-Derived Mesenchymal Stem Cells Enhances Mitigation of Chemotherapy-Induced Oral Mucositis

Zhang

Nguyen

Shi

et al. 2012

Stem Cells and Development

157

150

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Mesenchymal stem cells (MSCs) are capable of regenerative and immunomodulatory functions in cell-based therapies in a variety of human diseases and injuries; however, their therapeutic efficacy and potential side effects remain major obstacles in clinical applications. We report here a 3D spheroid culture approach to optimize stem cell properties and therapeutic effects of human gingiva-derived mesenchymal stem cells (GMSCs) in mitigation of experimental oral mucositis. Under growth condition of ultra-low attachment, GMSCs spontaneously aggregated into 3D spheroids and exhibited distinct early stem cell phenotype characterized by elevated expression Stro-1 and CXC chemokine receptor 4 (CXCR-4) as well as OCT-4 and Nanog, 2 important transcriptional factors relevant to stem cell properties, and decreased expression of MSC-associated markers, including CD29, CD90, and CD105. Functionally, spheroid GMSCs are capable of enhanced multipotency and augmented secretion of several chemokines and cytokines relevant to cell migration, survival, and angiogenesis. More importantly, spheroid GMSCs expressed increased levels of reactive oxygen species, hypoxia-inducible factor (HIF)-1 and -2a, and manganese superoxide dismutase, which correlated with improved resistance to oxidative stress-induced apoptosis. Using an in vivo murine model of chemotherapy-induced oral mucositis, we demonstrated that spheroid-derived GMSCs possessed better therapeutic efficacy than their adherent cells in reversing body weight loss and promoting the regeneration of disrupted epithelial lining of the mucositic tongues. These findings suggest that 3D spheroid culture allows early stemness preservation and potentially precondition GMSCs for enhanced mitigation of oral mucositis.

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Section: Discussionmentioning

confidence: 99%

Three-Dimensional Spheroid Culture of Human Gingiva-Derived Mesenchymal Stem Cells Enhances Mitigation of Chemotherapy-Induced Oral Mucositis

Zhang

Nguyen

Shi

et al. 2012

Stem Cells and Development

157

150

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“…Arguably the most abundant cell type in the TME, CAFs can be distinguished from other, normal fibroblasts thru their increased rate of proliferation and differential expression of extracellular matrix (ECM) components (Bhowmick, Neilson et al 2004;Kalluri and Zeisberg 2006;. It has been suggested at least in HNSCC, that resident and bone marrow (BM)-derived mesenchymal stem cells (MSCs) are actually precursors of the stroma and contribute to blood-and lymph angiogenesis, as well as produce tumor-associated (Hu, Castillo et al 2012) myofibroblasts (De Boeck, Narine et al 2010). Markers traditionally used to identify CAFs have been smooth muscle actin, vimentin and PDGFR but significant heterogeneity can be observed even in murine models of cancer suggesting that one marker alone will not identify all CAF in the TME (Sugimoto, Mundel et al 2006).…”

Section: The Tumor Microenvironmentmentioning

confidence: 99%

Tumour–stroma crosstalk in the development of squamous cell carcinoma

Lim

South

2014

The International Journal of Biochemistry & Cell Biology

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“…They are important modulators of tumor growth, invasion and metastasis producing extracellular matrix and angiogenic factors [10][11][12]. TAFs may be derived not only from the fibroblasts in the locoregional vicinity of the tumor but also from circulating mesenchymal stem cells [13,14]. TAFs are detected in both primary and metastatic HNSCC [15].…”

Section: Tumor Associated Fibroblastsmentioning

confidence: 99%