Article

Recapitulation of the embryonic cardiovascular progenitor cell niche

Department of Cell and Tissue Engineering, Fraunhofer IGB, 70569 Stuttgart, Germany.
Biomaterials (Impact Factor: 8.31). 04/2011; 32(11):2748-56. DOI: 10.1016/j.biomaterials.2010.12.046
Source: PubMed

ABSTRACT Stem or progenitor cell populations are often established in unique niche microenvironments that regulate cell fate decisions. Although niches have been shown to be critical for the normal development of several tissues, their role in the cardiovascular system is poorly understood. In this study, we characterized the cardiovascular progenitor cell (CPC) niche in developing human and mouse hearts, identifying signaling pathways and extracellular matrix (ECM) proteins that are crucial for CPC maintenance and expansion. We demonstrate that collagen IV (ColIV) and β-catenin-dependent signaling are essential for maintaining and expanding undifferentiated CPCs. Since niches are three-dimensional (3D) structures, we investigated the impact of a 3D microenvironment that mimics the in vivo niche ECM. Employing electrospinning technologies, 3D in vitro niche substrates were bioengineered to serve as culture inserts. The three-dimensionality of these structures increased mouse embryonic stem cell differentiation into CPCs when compared to 2D control cultures, which was further enhanced by incorporation of ColIV into the substrates. Inhibiting p300-dependent β-catenin signals with the small molecule IQ1 facilitated further expansion of CPCs. Our study represents an innovative approach to bioengineer cardiac niches that can serve as unique 3D in vitro systems to facilitate CPC expansion and study CPC biology.

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Available from: Katja Schenke-Layland, Aug 30, 2015
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    • "We have previously demonstrated that ICG-001 reduces the β-catenin/CBP interaction and thereby increases the β-catenin/p300 interaction in a variety of cell types [5], [9]. In contrast, IQ1, a specific small molecule antagonist of the β-catenin/p300 interaction has demonstrated the ability to maintain potency in stem/progenitor cell populations, including cardiovascular progenitors, by increasing the β-catenin/CBP interaction at the expense of the β-catenin/p300 interaction [9], [26]. In the event, we treated rat EMCs, an epicardial mesothelial cell line derived from an adult rat heart explant [27], with either ICG-001 or IQ1 and performed co-immunoprecipitation (co-IP) assays. "
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    • "As well, Flt1+/Flt4+ CPCs consistently formed beating colonies and CMs in vitro, which appeared to be more fetal in phenotype as seen on immunofluorescence staining (Fig. 4Ad; Figure S2), once transplanted in vivo, they formed CMs with a phenotype and electrophysiological properties typical of adult CMs (Fig. 6). The reason for this discrepancy is unclear, but external cues from the local microenvironment play a critical role in determining cell fate [16] and, a priori, intramyocardial injections would be predicted to favor cardiomyocyte differentiation. The local extracellular matrix along with electromechanical stimulation in vivo may play a role in evolving CMs to a more mature phenotype. "
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