The Globoseries Glycosphingolipid SSEA-4 Is a Marker of Bone Marrow-Derived Clonal Multipotent Stromal Cells In Vitro and In Vivo

Rosu‐Myles, Michael; McCully, Jennifer; Fair, Joel; Mehic, Jelica; Menéndez, Pablo; Westwood, Carole

doi:10.1089/scd.2012.0547

Cited by 22 publications

(28 citation statements)

References 29 publications

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“…These results support previous studies demonstrating germ cell colonization in mouse xenograft model following transplantation of primary SSEA-4+ sorted cells [35]. Interestingly, recent studies demonstrate that human bone marrow-derived mesenchymal stem cells (BmMSCs) also express SSEA-4 but lack CD45 expression [50]. Although CD45+ cells were excluded from any FACS analyses, we cannot eliminate the possibility of BmMSC contamination.…”

Section: Discussionsupporting

confidence: 87%

Testicular Niche Required for Human Spermatogonial Stem Cell Expansion

Smith

Yango

Altman

et al. 2014

Stem Cells Translational Medicine

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Prepubertal boys treated with high-dose chemotherapy do not have an established means of fertility preservation because no established in vitro technique exists to expand and mature purified spermatogonial stem cells (SSCs) to functional sperm in humans. In this study, we define and characterize the unique testicular cellular niche required for SSC expansion using testicular tissues from men with normal spermatogenesis. Highly purified SSCs and testicular somatic cells were isolated by fluorescence-activated cell sorting using SSEA-4 and THY1 as markers of SSCs and somatic cells. Cells were cultured on various established niches to assess their role in SSC expansion in a defined somatic cellular niche. Of all the niches examined, cells in the SSEA-4 population exclusively bound to adult testicular stromal cells, established colonies, and expanded. Further characterization of these testicular stromal cells revealed distinct mesenchymal markers and the ability to undergo differentiation along the mesenchymal lineage, supporting a testicular multipotent stromal cell origin. In vitro human SSC expansion requires a unique niche provided exclusively by testicular multipotent stromal cells with mesenchymal properties. These findings provide an important foundation for developing methods of inducing SSC growth and maturation in prepubertal testicular tissue, essential to enabling fertility preservation for these boys.

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Section: Discussionsupporting

confidence: 87%

Testicular Niche Required for Human Spermatogonial Stem Cell Expansion

Smith

Yango

Altman

et al. 2014

Stem Cells Translational Medicine

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“…The determination of cell surface markers is essential for basic studies and clinical applications. For the effective use of stem cells in cell therapy, it is necessary to know the pluripotency and multipotency associated glycans, for discrimination from other differentiated cells (145)(146)(147)). …”

Section: Resultsmentioning

confidence: 99%

Cell Surface Sialylated N-Glycan Alterations during Development

Karaçalı¹

2017

Eur J Biol

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This brief survey focuses on the comparison of sialylated N-glycans of embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), mesenchymal stem cells (MSCs) and of differentiated cells. In addition, the impact of sialic acid (Sia) deficiency on cell surfaces during development is summarized. The most common Sia is N-acetylneuraminic acid (Neu5Ac). The branched structures of complex-and hybrid-type N-glycans are the carrier for Sia. Transmembrane adhesive proteins, voltage-gated ion channels and many ligand-activated receptors are some examples of heavily sialylated N-glycan bearing membrane proteins. Their oligosaccharide extensions provide an important contribution to glycocalyx glycans. ESCs and iPSCs are characterized with high mannose-type and biantennary complex-type core structures. Two branches terminate with α2,6-linked Sia. MSCs contain high mannose, hybrid-and complex-type N-glycans. Linear poly-N-acetyllactosamine (poly-Galβ1-4GlcNAc, poly-LacNAc) chains are the characteristic structures. Both α2,3-and α2,6-linked Sias are seen in a species-specific manner in MSCs. α2,6-linked Sia is probably a marker associated with the multipotency of human MSCs. Differentiated healthy cells contain the most abundant 2-branched complex structures. The bisecting branch on the core structure appears as a differentiation marker. poly-LacNAc chains are terminated with α2,3-and α2,6-linked Sia, with the former being higher. poly-LacNAc sequences have a high affinity for β-galactoside recognizing lectin and galectin. Galectin forms a lattice structure with the N-glycans of glycoproteins anchored to the plasma membrane. The impact of N-glycangalectin complexes in cell biology is summarized. Finally, the effect of reduced Sia on clearance of aged cells is explained. Experimental evidence for the masking role of Sia in the regulation of histolysis in aged cells is revealed.

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“…We analysed TRA-1-85 high cells for the expression of multipotent stromal cell marker SSEA4 [ 55 ], pericyte, and adult stem cell marker CD146 [ 56 ], as well as cardiomyocyte markers SIRPA and CX43 using FC. The majority of TRA-1-85 high MSCs (FTM, term, and BMSC) significantly downregulated SSEA4 expression in both direct coculture and aggregate coculture when compared to undifferentiated cells ( Figure 2(a) , p < 0.01).…”

Section: Resultsmentioning

confidence: 99%

In Vitro Differentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte‐Like Cells

Száraz

Librach

Maghen

et al. 2016

Stem Cells International

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Myocardial infarction (MI) causes an extensive loss of heart muscle cells and leads to congestive heart disease (CAD), the leading cause of mortality and morbidity worldwide. Mesenchymal stromal cell- (MSC-) based cell therapy is a promising option to replace invasive interventions. However the optimal cell type providing significant cardiac regeneration after MI is yet to be found. The aim of our study was to investigate the cardiomyogenic differentiation potential of first trimester human umbilical cord perivascular cells (FTM HUCPVCs), a novel, young source of immunoprivileged mesenchymal stromal cells. Based on the expression of cardiomyocyte markers (cTnT, MYH6, SIRPA, and CX43) FTM and term HUCPVCs achieved significantly increased cardiomyogenic differentiation compared to bone marrow MSCs, while their immunogenicity remained significantly lower as indicated by HLA-A and HLA-G expression and susceptibility to T cell mediated cytotoxicity. When applying aggregate-based differentiation, FTM HUCPVCs showed increased aggregate formation potential and generated contracting cells within 1 week of coculture, making them the first MSC type with this ability. Our results indicate that young FTM HUCPVCs have superior cardiomyogenic potential coupled with beneficial immunogenic properties when compared to MSCs of older tissue sources, suggesting that in vitro predifferentiation could be a potential strategy to increase their effectiveness in vivo.

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The Globoseries Glycosphingolipid SSEA-4 Is a Marker of Bone Marrow-Derived Clonal Multipotent Stromal Cells In Vitro and In Vivo

Cited by 22 publications

References 29 publications

Testicular Niche Required for Human Spermatogonial Stem Cell Expansion

Testicular Niche Required for Human Spermatogonial Stem Cell Expansion

Cell Surface Sialylated N-Glycan Alterations during Development

In Vitro Differentiation of First Trimester Human Umbilical Cord Perivascular Cells into Contracting Cardiomyocyte‐Like Cells

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