Human placenta and bone marrow derived MSC cultured in serum-free, b-FGF-containing medium express cell surface frizzled-9 and SSEA-4 and give rise to multilineage differentiation

Battula, Venkata Lokesh; Bareiss, Petra M.; Treml, Sabrina; Conrad, Sabine; Albert, Ingrid; Hojak, Sigrid; Abele, Harald; Schewe, B.; Just, Lothar; Skutella, Thomas; Bühring, Hans Jörg

doi:10.1111/j.1432-0436.2006.00139.x

Cited by 242 publications

(201 citation statements)

References 32 publications

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“…W8B2 1 CD56 1 BMSCs can undergo osteoblastic, chondrogenic, myogenic, neuronal, and pancreatic differentiation, while adipocyte differentiation potential is restricted to the W8B2 1 CD56 2 subset of BMSCs [12,13]. Here, we report a population of CRSCs isolated from human adult atrial appendages which are positive for the W8B2 antigen.…”

Section: Introductionmentioning

confidence: 84%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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Cardiac resident stem cells (CRSCs) hold much promise to treat heart disease but this remains a controversial field. Here, we describe a novel population of CRSCs, which are positive for W8B2 antigen and were obtained from adult human atrial appendages. W8B2 1 CRSCs exhibit a spindle-shaped morphology, are clonogenic and capable of self-renewal. W8B2 1 CRSCs show high expression of mesenchymal but not hematopoietic nor endothelial markers. W8B2 1 CRSCs expressed GATA4, HAND2, and TBX5, but not C-KIT, SCA-1, NKX2.5, PDGFRa, ISL1, or WT1. W8B2 1 CRSCs can differentiate into cardiovascular lineages and secrete a range of cytokines implicated in angiogenesis, chemotaxis, inflammation, extracellular matrix remodeling, cell growth, and survival. In vitro, conditioned medium collected from W8B2 1 CRSCs displayed prosurvival, proangiogenic, and promigratory effects on endothelial cells, superior to that of other adult stem cells tested, and additionally promoted survival and proliferation of neonatal rat cardiomyocytes. Intramyocardial transplantation of human W8B2 1 CRSCs into immunocompromised rats 1 week after myocardial infarction markedly improved cardiac function (~40% improvement in ejection fraction) and reduced fibrotic scar tissue 4 weeks after infarction. Hearts treated with W8B2 1 CRSCs showed less adverse remodeling of the left ventricle, a greater number of proliferating cardiomyocytes (Ki67 1 cTnT 1 cells) in the remote region, higher myocardial vascular density, and greater infiltration of CD163 1 cells (a marker for M2 macrophages) into the border zone and scar regions. In summary, W8B2 1 CRSCs are distinct from currently known CRSCs found in human hearts, and as such may be an ideal cell source to repair myocardial damage after infarction. STEM CELLS 2015;33:3100-3113 SIGNIFICANCE STATEMENTWe have isolated a new type of adult stem cell from human heart tissue, which carries markers different from known cardiac resident stem cells. These cells can be rapidly expanded and have powerful regenerative effects when injected into the hearts of rats after heart attack, such that they greatly improve cardiac performance compared with controls that have also suffered heart attack. We showed these cells protect other cells from dying and promote growth of blood vessels, actions which assist cardiac regeneration. Importantly, their protective actions in this regard are superior to those of other adult stem cells that have shown some benefit in clinical trials after heart attack. These new stem cells have great potential for repairing the heart, and could be derived from the individual patients in need, avoiding any problem of immunorejection.

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Section: Introductionmentioning

confidence: 84%

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

et al. 2015

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“…However, Gang et al reported that SSEA-4 are expressed on human BM-derived MSCs [29]. These differences might be due to differences in the derivation methodologies used by different groups; for example, Battula et al showed that culturing human placenta or BM-derived MSCs in serum-free bFGF-containing medium induces expression of SSEA-4 [30]. Shibata et al have shown that purging SSEA-4 positive cells from hematopoietic cells differentiated from cynomolgus monkey ESCs prevented teratoma formation when cells were subsequently transplanted into fetal animals, compared to transplantation of un-purged cells that resulted in teratoma formation in all animals tested [31].…”

Section: Discussionmentioning

confidence: 99%

“…We used the WiCell human ESC cell lines H1 (WA01), H7 (WA07) and H9 (WA09), passages [25][26][27][28][29][30][31][32][33][34][35], that were originally maintained on murine embryonic fibroblast (MEF) cells. Prior to the differentiation experiments, we passaged these cells weekly for several times on matrigelcoated plates with daily change of media consisting of MEF conditioned media (CM) + basic fibroblast growth factor (bFGF, R&D Systems) to ensure the absence of MEF cells in the culture plates.…”

Section: Materials and Methods Hesc Culturesmentioning

confidence: 99%

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

Trivedi

Hematti

2008

Experimental Hematology

176

159

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Objective-We have previously shown the simultaneous generation of CD73+ mesenchymal stromal cells (MSCs) along with CD34+ hematopoietic cells from human embryonic stem cells (ESCs) when they are co-cultured with OP9 murine stromal cells. We investigated whether MSCs can be derived from human ESCs without co-culturing with OP9 cells, and if such cells exhibit immunological properties similar to MSCs derived from adult human bone marrow (BM).Materials and Methods-Our starting populations were undifferentiated ESCs cultured on matrigel-coated plates without feeder cells. The differentiated fibroblast-looking cells were tested for expression of MSC markers and their potential for multi-lineage differentiation. We investigated surface expression of HLA molecules on these MSCs before and after treatment with interferon gamma (IFN-γ). We also tested the proliferative response of T-lymphocytes towards MSCs and the effects of MSCs in mixed lymphocyte reaction (MLR) assays. Conclusions-MSCs can be derived from human ESCs without feeder cells. These human ESCderived MSCs have cell surface markers, differentiation potentials, and immunological properties in vitro that are similar to adult BM-derived MSCs. Results-We

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“…Nevertheless, alternative sources of growth supplements are being investigated. Replacement of FBS with pooled allogeneic AB serum (Kocaoemer et al, 2007;Kunisaki et al, 2007), thrombin-activated platelet-rich plasma (KocaoemerÄet al, 2007), human platelet lysate (Lange et al, 2007;Schallmoser et al, 2007), or bovine fibroblast growth factor (Battula et al, 2007) supports equal or greater proliferation and/or multilineage differentiation of human BM-, adipose-or amniotic fluid-derived MSCs (Mannello and Tonti, 2007). BMMSCs expanded in medium containing autologous serum (AS) proliferate faster and differentiate less rapidly than cells cultured with FBS .…”

Section: Introductionmentioning

confidence: 99%

Genetic and epigenetic instability of human bone marrow mesenchymal stem cells expanded in autologous serum or fetal bovine serum

Dahl

Duggal²,

Coulston³

et al. 2008

Int. J. Dev. Biol.

163

119

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Culture of mesenchymal stem cells (MSCs) under conditions promoting proliferation and differentiation, while supporting genomic and epigenetic stability, is essential for therapeutic use. We report here the extent of genome-wide DNA gains and losses and of DNA methylation instability on 170 cancer-related promoters in bone marrow (BM) MSCs during culture to late passage in medium containing fetal bovine serum (FBS) or autologous serum (AS). Comparative genomic hybridization indicates that expansion of BMMSCs elicits primarily telomeric deletions in a subpopulation of cells, the extent of which varies between donors. However, late passage cultures in AS consistently display normal DNA copy numbers. Combined bisulfite restriction analysis and bisulfite sequencing show that although DNA methylation states are overall stable in culture, AS exhibits stronger propensity than FBS to maintain unmethylated states. Comparison of DNA methylation in BMMSCs with freshly isolated and cultured adipose stem cells (ASCs) also reveals that most genes unmethylated in both BMMSCs and ASCs in early passage are also unmethylated in uncultured ASCs. We conclude that (i) BMMSCs expanded in AS or FBS may display localized genetic alterations, (ii) AS tends to generate more consistent genomic backgrounds and DNA methylation patterns, and (iii) the unmethylated state of uncultured MSCs is more likely to be maintained in culture than the methylated state.

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Human placenta and bone marrow derived MSC cultured in serum-free, b-FGF-containing medium express cell surface frizzled-9 and SSEA-4 and give rise to multilineage differentiation

Cited by 242 publications

References 32 publications

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Cardiac Repair With a Novel Population of Mesenchymal Stem Cells Resident in the Human Heart

Derivation and immunological characterization of mesenchymal stromal cells from human embryonic stem cells

Genetic and epigenetic instability of human bone marrow mesenchymal stem cells expanded in autologous serum or fetal bovine serum

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