VEGF is critical for spontaneous differentiation of stem cells into cardiomyocytes

Song, Yao‐Hua; Gehmert, Sebastian; Sadat, Sanga; Pinkernell, Kai; Bai, Xiaowen; Matthias, Nadine; Alt, Eckhard

doi:10.1016/j.bbrc.2007.01.095

Cited by 116 publications

(80 citation statements)

References 17 publications

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“…Although some studies have previously described the differentiation of human ASCs towards cardiomyocytes Song et al 2007), this is the first time, to the best of our knowledge, that such a large number of human ASCs has been shown to differentiate along this route. Notably, we have demonstrated this effect in cells derived from several donors.…”

Section: Discussionmentioning

confidence: 70%

“…Furthermore, in vivo animal studies, in which ASCs have been transplanted after MI, have also shown the differentiation of ASCs towards cardiomyocytes and increased cardiac function (Strem et al 2005;Zhang et al 2007). However, studies on human ASCs are limited, and only low percentages (<2%) of spontaneous differentiation have been described Song et al 2007). Only Gaustad et al (2004) have described a higher differentiation rate (25% desmin-positive cells) of human ASCs in vitro, but only in one donor and only after the cells had been permeabilized and exposed to extracts of rat cardiomyocytes.…”

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confidence: 99%

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Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin

et al. 2008

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Adipose-derived stem cells (ASCs) are promising candidates for therapy in myocardial infarction (MI). However, the frequency of human ASCs that differentiate towards cardiomyocytes is low. We hypothesized that adherence to extracellular matrix molecules that are upregulated after MI might increase human stem cell differentiation towards cardiomyocytes. We analysed putative ASC differentiation on fibronectin-coated, laminincoated and uncoated culture plates. Expression of cardiac markers in cells was analysed 1, 3 and 5 weeks after stimulation with 5-aza-2-deoxycytidine. After 1 week, mRNA expression of myosin light chain-2α (MLC-2α), an early marker in cardiomyocyte development, was increased significantly in treated cells, independent of coating. At 5 weeks, however, mRNA expression of the late cardiomyocyte development marker SERCA2α was only significantly increased in 5-aza-2-deoxycytidine-treated cells cultured on laminin. Significantly higher numbers of cells were immunopositive for MLC-2α in cultures of treated cells grown on laminin-coated wells, when compared with cultures of treated cells grown on uncoated wells, both at 1 week and at 5 weeks. Furthermore, after 3 weeks, significantly more α-actinin-and desmin-positive cells were detected after treatment with 5-aza-2-deoxycytidine, but only in uncoated wells. After 5 weeks, however, the number of desmin-positive cells was only significantly increased after treatment of cells with 5-aza-2-deoxycytidine and culture on laminin (61% positive cells). Thus, we have found that a high percentage of human ASCs can be differentiated towards cardiomyocytes; this effect can be improved by laminin, especially during late differentiation.

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Section: Discussionmentioning

confidence: 70%

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confidence: 99%

Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin

et al. 2008

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“…PI3K catalytic subunit p110a and p110 are essential for cardiovascular differentiation upon treatment of EBs with VEGF As previously described, VEGF plays a crucial role in cardiac and vascular differentiation, and acts on Flk-1 + cardiovascular progenitor cells (Chen et al, 2006;Cheung, 1997;Gerber et al, 1998;Gliki et al, 2002;Song et al, 2007;Yang et al, 2002;Zisa et al, 2009;Lange et al, 2009). To investigate whether PI3K class IA isoforms are essential for VEGF signaling pathways leading to cardiac and vascular differentiation of ES cells, p110a, p110b and p110 gene-inactivated EBs were treated from day 4 to day 10 of cell culture with VEGF (500 pM).…”

Section: Pharmacological Inhibition Of Pi3ks and Targeting Of Class Imentioning

confidence: 78%

“…Previous studies showed that VEGF is essential for cardiomyogenesis and/or vascular differentiation (Chen et al, 2006;Cheung, 1997;Gerber et al, 1998;Gliki et al, 2002;Song et al, 2007;Yang et al, 2002;Zisa et al, 2009;Lange et al, 2009;Bekhite et al, 2010) and might activate PI3K (Bos 1995;Gerber et al, 1998). Moreover, it has been suggested that Flk-1 + plays a crucial role in regulating PI3K activity in endothelial cells (Gerber et al, 1998;Ferrara, 1999;Thomas and Owen, 2008).…”

Section: Discussionmentioning

confidence: 99%

VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells

Bekhite

Finkensieper

Binas

et al. 2011

Journal of Cell Science

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SummaryVEGF-, phosphoinositide 3-kinase (PI3K)-and protein kinase C (PKC)-regulated signaling in cardiac and vascular differentiation was investigated in mouse ES cells and in ES cell-derived Flk-1 + cardiovascular progenitor cells. Inhibition of PI3K by wortmannin and LY294002, disruption of PI3K catalytic subunits p110a and p110 using short hairpin RNA (shRNA), or inhibition of p110a with compound 15e and of p110 with IC-87114 impaired cardiac and vascular differentiation. By contrast, TGX-221, an inhibitor of p110b, and shRNA knockdown of p110b were without significant effects. Antagonists of the PKC family, i.e. bisindolylmaleimide-1 (BIM-1), GÖ 6976 (targeting PKCa/bII) and rottlerin (targeting PKC) abolished vasculogenesis, but not cardiomyogenesis. Inhibition of Akt blunted cardiac as well as vascular differentiation. VEGF induced phosphorylation of PKCa/bII and PKC but not PKCz. This was abolished by PI3K inhibitors and the VEGFR-2 antagonist SU5614. Furthermore, phosphorylation of Akt and phosphoinositidedependent kinase-1 (PDK1) was blunted upon inhibition of PI3K, but not upon inhibition of PKC by BIM-1, suggesting that activation of Akt and PDK1 by VEGF required PI3K but not PKC. In summary, we demonstrate that PI3K catalytic subunits p110a and p110 are central to cardiovasculogenesis of ES cells. Akt downstream of PI3K is involved in both cardiomyogenesis and vasculogenesis, whereas PKC is involved only in vasculogenesis.

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“…Vascular endothelial growth factor (VEGF) functions in the angiogenesis in the early embryo. In vitro, VEGF stimulates the proliferation and migration of endothelial cells and plays an important role for spontaneous and damage-induced differentiation of adult cardiomyocyte progenitors into cardiomyocytes [94,107,108]. VEGF is typically not included in nutrient mediums and must be added manually.…”

Section: Cardiomyocytes Derived By Reprogramming Of Somatic Cellsmentioning

confidence: 99%

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

Arabadjiev¹,

Petkova²,

Chakarov³

et al. 2014

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Citation: Arabadjiev A, Petkova R, Chakarov S, Pankov R, Zhelev N. We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells. AbstractHuman cell lines, including disease cell lines are often superior to routine animal models for the purposes of rapid and safe assessment of the effects of different agents that may modulate myocardial functioning under physiological and pathological conditions. There are several currently existing methodologies for derivation of cardiomyocyte-like cells by targeted differentiation from pluripotent cells and by reprogramming/ transdifferentiation from other types of cells (multipotent progenitors, somatic cells, etc). The present paper reviews the potential sources of cells capable of differentiation along the cardiomyocyte lineage; the existing methodologies for targeted differentiation, outlining the specificities of each method; and the markers for differentiation along the mesodermal and the cardiogenic lineage. The yield of robustly beating cells expressing cardio-specific proteins derived by any of the existing methods, however, still rarely exceeds 70-90 %, even with the newly developed approaches for increasing the differentiation capacity. There still is significant variance in the results obtained by different research groups and even between different experiments carried out in the same laboratory, with the same type of cells and same general type of protocol. Derivation of new lines of human pluripotent and multipotent stem cells according to standardised protocols and in completely defined; xeno-free conditions may increase the reliability and reproducibility of research and speed up the development of potential clinical applications.

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VEGF is critical for spontaneous differentiation of stem cells into cardiomyocytes

Cited by 116 publications

References 17 publications

Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin

Differentiation of human adipose-derived stem cells towards cardiomyocytes is facilitated by laminin

VEGF-mediated PI3K class IA and PKC signaling in cardiomyogenesis and vasculogenesis of mouse embryonic stem cells

We heart cultured hearts. A comparative review of methodologies for targeted differentiation and maintenance of cardiomyocytes derived from pluripotent and multipotent stem cells

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