Regulation of stemness and stem cell niche of mesenchymal stem cells: Implications in tumorigenesis and metastasis

Kuhn, Nastaran Z.; Tuan, Rocky S.

doi:10.1002/jcp.21940

Cited by 240 publications

(196 citation statements)

References 175 publications

(167 reference statements)

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“…As biochemical and mechanical factors infl uencing MSC fate within their native environment are different from those used in tissue regeneration strategies and cell culture studies in vitro, it is likely that approaches for bone tissue regeneration would be enhanced if the in vivo environment was better understood. In vivo, MSCs are found within a unique environment known as the stem cell niche (Li and Xie, 2005). The stem cell niche in bone consists of a host of different support cells including haematopoietic progenitors and their progeny -such as blood cells, immune cells, and osteoclasts -and MSCs and their progeny, including fibroblasts, endothelial cells, adipocytes, osteoblasts, as well as osteocytes found embedded in bone (Kuhn and Tuan, 2010).…”

Section: Of Mscs In a Simplifi Ed Bone Nichementioning

confidence: 99%

Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche

Birmingham

Niebur²,

McHugh³

et al. 2012

eCM

434

340

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Mesenchymal stem cells (MSCs) within their native environment of the stem cell niche in bone receive biochemical stimuli from surrounding cells. These stimuli likely infl uence how MSCs differentiate to become bone precursors. The ability of MSCs to undergo osteogenic differentiation is well established in vitro; however, the role of the natural cues from bone's regulatory cells, osteocytes and osteoblasts in regulating the osteogenic differentiation of MSCs in vivo are unclear. In this study we delineate the role of biochemical signalling from osteocytes and osteoblasts, using conditioned media and co-culture experiments, to understand how they direct osteogenic differentiation of MSCs. Furthermore, the synergistic relationship between osteocytes and osteoblasts is examined by transwell co-culturing of MSCs with both simultaneously. Osteogenic differentiation of MSCs was quantified by monitoring alkaline phosphatase (ALP) activity, calcium deposition and cell number. Intracellular ALP was found to peak earlier and there was greater calcium deposition when MSCs were co-cultured with osteocytes rather than osteoblasts, suggesting that osteocytes are more infl uential than osteoblasts in stimulating osteogenesis in MSCs. Osteoblasts initially stimulated an increase in the number of MSCs, but ultimately regulated MSC differentiation down the same pathway. Our novel coculture system confi rmed a synergistic relationship between osteocytes and osteoblasts in producing biochemical signals to stimulate the osteogenic differentiation of MSCs. This study provides important insights into the mechanisms at work within the native stem cell niche to stimulate osteogenic differentiation and outlines a possible role for the use of co-culture or conditioned media methodologies for tissue engineering applications.

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Section: Of Mscs In a Simplifi Ed Bone Nichementioning

confidence: 99%

Osteogenic differentiation of mesenchymal stem cells is regulated by osteocyte and osteoblast cells in a simplified bone niche

Birmingham

Niebur²,

McHugh³

et al. 2012

eCM

434

340

View full text Add to dashboard Cite

show abstract

“…The cellular and non-cellular components of the niche provide cues that regulate proliferative and self renewal signals, thereby helping cencer stem cells maintain their undifferentiated state (Kuhn et al, 2010). Non-epithelial stromal cells, inflammatory cells and the vasculature have been proposed as key components of the niche that support and sustain cancer stem cells (Fuchs et al, 2004).…”

Section: Stem Cell Nichementioning

confidence: 99%

Cancer Stem Cells in Head and Neck Squamous Cell Carcinoma: A Review

Satpute

Hazarey²,

Ahmed³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Research indicates that a small population of cancer cells is highly tumorigenic, endowed with the capacity for self-renewal, and has the ability to differentiate into cells that constitute the bulk of tumors. These cells are considered the ''drivers'' of the tumorigenic process in some tumor types, and have been named cancer stem cells (CSC). Epithelial-mesenchymal transition (EMT) appears to be involved in the process leading to the acquisition of stemness by epithelial tumor cells. Through this process, cells acquire an invasive phenotype that may contribute to tumor recurrence and metastasis. CSC have been identified in human head and neck squamous cell carcinomas (HNSCC) using markers such as CD133 and CD44 expression, and aldehyde dehydrogenase (ALDH) activity. Head and neck cancer stem cells reside primarily in perivascular niches in the invasive fronts where endothelial-cell initiated events contribute to their survival and function. Clinically, CSC enrichment has been shown to be enhanced in recurrent disease, treatment failure and metastasis. CSC represent a novel target of study given their slow growth and innate mechanisms conferring treatment resistance. Further understanding of their unique phenotype may reveal potential molecular targets to improve therapeutic and survival outcomes in patients with HNSCC. Here, we discuss the state-of-the-knowledge on the pathobiology of cancer stem cells, with a focus on the impact of these cells on head and neck tumor progression, metastasis and recurrence due to treatment failure.

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“…We cannot predict the extent of the paracrine effect, immunomodulatory, or if the effective replenishment of differentiated cells can be assigned, in each case, to the MSCs, or whether these effects have some degree of integration between them. We cannot even know if all those effects can influence the surrounding tissue positively during regeneration, but perhaps negatively towards the pathogenesis of cancer and metastasis (Kuhn & Tuan, 2010). For now, we can only say that in many cases, these actions have a certain synergy to the purpose they claim.…”

Section: Resultsmentioning

confidence: 97%