Novel 3D Culture System with Similarities to the Human Heart for Studies of the Cardiac Stem Cell Niche

Jönsson, Mikael; Henriksson, Helena Barreto; Hagman, Marianne; Kajic, Kristina; Lindahl, Anders; Jeppsson, Anders; Berggren, Håkan; Asp, Julia

doi:10.2217/rme.10.63

Cited by 7 publications

(14 citation statements)

References 35 publications

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“…Although differences in expression patterns between RA and LV were observed for specific genes related to development, cardiac stem or progenitor cell markers such as C-KIT or OCT4, previously reported to be expressed in cardiac biopsies from the same group of patients (12,23), were, in this study, not identified as differentially expressed between the studied locations. This suggests that these cells are present in both locations.…”

Section: Discussioncontrasting

confidence: 80%

“…The following TaqMan Gene Expression Assays were used: ALOX15 Hs00609608_m1, C3 Hs01100879_m1, FOS Hs00170630_m1, HLA-DRA Hs00219575_m1, PLA2G2A Hs00179898_m1, PLA2G4A Hs00233352_m1, PTGS1 Hs00377726_m1, PTGS2 Hs00153133_m1, STAT6 Hs00598625_m1, TPM2 Hs00268540_m1. CREBBP Hs00231733_m1 was used as a reference gene (12). Samples were analyzed in duplicates using the instrument 7900HT.…”

Section: Validation By Quantitative Real-time Pcrmentioning

confidence: 99%

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Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo

Asp

Synnergren

Jönsson

et al. 2012

Physiological Genomics

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Section: Discussioncontrasting

confidence: 80%

Section: Validation By Quantitative Real-time Pcrmentioning

confidence: 99%

Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo

Asp

Synnergren

Jönsson

et al. 2012

Physiological Genomics

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“…In cardiac progenitor populations, the data on the expression of OCT-4 are more inconsistent. We and others have previously reported expression of OCT-4 in these populations [2,21], while others have failed to detect this expression [37,41]. It could be hypothesized that OCT-4 expression may be of importance to keep certain cardiac progenitor populations, including SP cells, in an undifferentiated state.…”

Section: Discussionmentioning

confidence: 81%

“…The following human TaqMan Gene Expression Assays were used: ABCG2 Hs01053796_m1, MDR1 Hs00184500_m1, C-KIT Hs00174029_m1, OCT-4 Hs01895061_u1, CD31 Hs0016 9777_m1, FLK1 Hs00176676_m1, VWF Hs00169795_m1, NKX2.5 Hs00231763_m1, and TNNT2 Hs00165960_m1. CREBBP Hs00231733_m1 was used as a reference gene [21]. The samples were analyzed in duplicates using the 7900HT instrument.…”

Section: Quantitative Real-time Pcr Analysismentioning

confidence: 99%

Left atrium of the human adult heart contains a population of side population cells

et al. 2012

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Cardiac "side population" (SP) cells have previously been found to differentiate into both endothelial cells and cardiomyocytes in mice and rats, but there are no data on SP cells in the human adult heart. Therefore, human cardiac atrial biopsies were dissociated, stained for SP cells and analyzed with FACS. Identified cell populations were analyzed for gene expression by quantitative real-time PCR and subjected to in vitro differentiation. Only biopsies from the left atrium contained a clearly distinguishable population of SP cells (0.22 ± 0.08%). The SP population was reduced by co-incubation with MDR1 inhibitor Verapamil, while the ABCG2 inhibitor FTC failed to decrease the number of SP cells. When the gene expression was analyzed, SP cells were found to express significantly more MDR1 than non-SP cells. For ABCG2, there was no detectable difference. SP cells also expressed more of the stem cell-associated markers C-KIT and OCT-4 than non-SP cells. On the other hand, no significant difference in the expression of endothelial and cardiac genes could be detected. SP cells were further subdivided based on CD45 expression. The CD45-SP population showed evidence of endothelial commitment at gene expression level. In conclusion, the results show that a SP population of cells is present also in the human adult heart.

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“…Cultures of cardiospheres where cells have migrated and self-organized into spheres [14–16] have shown an increase in the expression of progenitor markers such as C-KIT , but the cardiomyogenic potential of cells from these kind of cultures has been questioned [17]. In our previous study [18], we described a novel 3D model of high density spheres (HDS) cultured with or without cardiomyocytes. Results from that study suggested that this 3D model could harbor and nourish CPC, in which marker expression increased with culture time.…”

Section: Introductionmentioning

confidence: 99%

High Density Sphere Culture of Adult Cardiac Cells Increases the Levels of Cardiac and Progenitor Markers and Shows Signs of Vasculogenesis

Vukusic

Jönsson

Brantsing

et al. 2013

BioMed Research International

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3D environment and high cell density play an important role in restoring and supporting the phenotypes of cells represented in cardiac tissues. The aim of this study was therefore to investigate the suitability of high density sphere (HDS) cultures for studies of cardiomyocyte-, endothelial-, and stem-cell biology. Primary adult cardiac cells from nine human biopsies were cultured using different media for up to 9 weeks. The possibilities to favor a certain cell phenotype and induce production of extra cellular matrix (ECM) were studied by histology, immunohistochemistry, and quantitative real-time PCR. Defined media gave significant increase in both cardiac- and progenitor-specific markers and also an intraluminal position of endothelial cells over time. Cardiac media showed indication of differentiation and maturity of HDS considering the ECM production and activities within NOTCH regulation but no additional cardiac differentiation. Endothelial media gave no positive effects on endothelial phenotype but increased proliferation without fibroblast overgrowth. In addition, indications for early vasculogenesis were found. It was also possible to affect the Wnt signaling in HDS by addition of a glycogen synthase kinase 3 (GSK3) inhibitor. In conclusion, these findings show the suitability of HDS as in vitro model for studies of cardiomyocyte-, endothelial-, and stem-cell biology.

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Novel 3D Culture System with Similarities to the Human Heart for Studies of the Cardiac Stem Cell Niche

Abstract: The described 3D culture model could be a valuable tool when studying the influence of different compounds on proliferation and differentiation processes in cardiac stem or progenitor cells in cardiac regenerative research.

Cited by 7 publications

References 35 publications

Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo

Comparison of human cardiac gene expression profiles in paired samples of right atrium and left ventricle collected in vivo

Left atrium of the human adult heart contains a population of side population cells

High Density Sphere Culture of Adult Cardiac Cells Increases the Levels of Cardiac and Progenitor Markers and Shows Signs of Vasculogenesis

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