Neural Ganglioside GD2⁺Cells Define a Subpopulation of Mesenchymal Stem Cells in Adult Murine Bone Marrow

Abstract

Background/Aims: Due to the lack of specific markers, the isolation of pure mesenchymal stem cells (MSCs) from murine bone marrow remains an unsolved problem. The present study explored whether the neural ganglioside GD2 could serve as a single surface marker to uniquely distinguish murine bone marrow MSCs (mBM-MSCs) from other marrow elements. Methods: Immunocytochemistry and flow cytometry, in combination with quantitative RT-PCR, were used to identify the expression of GD2 on culture-expanded mBM-MSCs. GD2⁺ and GD2^- fractions from mBM-MSCs cultures were sorted by immunosorting. Flow cytometry was performed to further analyze the biomarkers of GD2-sorted and unsorted cells. Employing CFU-F assay and CCK-8 assay, we examined the clonogenic and proliferative capabilities of GD2-sorted and unsorted cells. Using oil red O and von Kossa staining assay, we also assessed the multi-lineage potential of GD2-sortedand unsorted cells. Results: We found that mBM-MSCs expressed a novel surface marker the neural ganglioside GD2. Importantly, mBM-MSCs were the only cells within bone marrow that expressed this marker. Further studies demonstrated that a homogenous population of MSCs could be obtained from bone marrow cultures in early passages by GD2 immunosorting. Compared to parental cells, GD2⁺-sorted cells not only possessed much higher clonogenic and proliferative capabilities but also had significantly stronger differentiation potential to adipocytes and osteoblasts. Furthermore, GD2⁺-sorted cells displayed enhanced expression of ES markers SSEA-1 and Nanog. Conclusion: Our observations provide the first demonstration that GD2 may serve as a maker for identification and purification of mBM-MSCs. Meanwhile, our study indicates that the cells selected by GD2 are a subpopulation of MSCs with features of primitive precursor cells.

Identification and Characterization of Cancer Stem Cells from Head and Neck Squamous Cell Carcinoma Cell Lines

“…Both SCs [41] and CSCs were identified since they were found to express specific cell-surface markers. A lot of studies have identified CSC markers across a variety of solid cancers, but relatively few of these markers have been studied in HNSCC, and the putative CSCs from HNSCC have not been well characterized [42][43][44].…”

Fat for fuel: lipid metabolism in haematopoiesis

“…The importance of these stromal‐derived lipids has been demonstrated in both myelopoiesis and lymphopoiesis in vitro and in vivo . BM stromal cells express gangliosides in both humans and mice . Xu et al .…”

“…Xu et al . have shown that ganglioside‐expressing murine stromal cells exhibit a stronger proliferative phenotype . These cells differentiate more readily into adipocytes and osteoblasts, cellular components of the BM niche that support haematopoiesis and are likely leptin receptor + mesenchymal stromal cells or a subset thereof (Figure aii).…”

“…[33][34][35] Xu et al have shown that ganglioside-expressing murine stromal cells exhibit a stronger proliferative phenotype. 34 These cells differentiate more readily into adipocytes and osteoblasts, cellular components of the BM niche that support haematopoiesis and are likely leptin receptor + mesenchymal stromal cells or a subset thereof ( Figure 3aii). Further, the transport of GM3 into myeloid progenitors has been suggested to sustain lipid raft formation, allowing for enhanced granulocyte-macrophage (GM)-CSF signalling, thus enhancing myeloid proliferation.…”

Ginsenoside Rh2 Inhibits Cancer Stem-Like Cells in Skin Squamous Cell Carcinoma

“…Skin SCC causes a lot of mortality yearly, which requires a better understanding of the molecular carcinogesis of skin SCC for developing efficient therapy [1,2]. Ginsenoside Rh2 (GRh2) is a characterized component in red ginseng, and has proven therapeutic effects on inflammation [3] and a number of cancers [4][5][6][7][8][9][10][11][12][13][14], whereas its effects on the skin SCC have not been examined.…”