Origins and Fates of Cardiovascular Progenitor Cells
ABSTRACT Multipotent cardiac progenitor cells are found in the fetal and adult heart of many mammalian species including humans and form as intermediates during the differentiation of embryonic stem cells. Despite similar biological properties, the molecular identities of these different cardiac progenitor cell populations appear to be distinct. Elucidating the origins and lineage relationships of these cell populations will accelerate clinical applications such as drug screening and cell therapy as well as shedding light on the pathogenic mechanisms underlying cardiac diseases.
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Article: Origins and Fates of Cardiovascular Progenitor Cells
- SourceAvailable from: Yacine Kharraz
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- "Unlike organs such as kidney or heart, where distinct cell types have been shown to contribute to fibrosis [73, 74], in skeletal muscle very little is known about the role of other cell lineages in fibrosis development and their potential contribution to the pool of fibroblasts. However, although MSCs are probably the main source of fibroblasts within the dystrophic muscle, additional studies suggest that other cells might also contribute to fibrosis in pathological contexts. "
ABSTRACT: Fibrosis is the aberrant deposition of extracellular matrix (ECM) components during tissue healing leading to loss of its architecture and function. Fibrotic diseases are often associated with chronic pathologies and occur in a large variety of vital organs and tissues, including skeletal muscle. In human muscle, fibrosis is most readily associated with the severe muscle wasting disorder Duchenne muscular dystrophy (DMD), caused by loss of dystrophin gene function. In DMD, skeletal muscle degenerates and is infiltrated by inflammatory cells and the functions of the muscle stem cells (satellite cells) become impeded and fibrogenic cells hyperproliferate and are overactivated, leading to the substitution of skeletal muscle with nonfunctional fibrotic tissue. Here, we review new developments in our understanding of the mechanisms leading to fibrosis in DMD and several recent advances towards reverting it, as potential treatments to attenuate disease progression.BioMed Research International 05/2014; 2014(3):965631. DOI:10.1155/2014/965631 · 2.71 Impact Factor
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- "Cardiovascular progenitor cells (CPCs) are the building blocks of the heart, and have the potential to form cardiomyocytes, endocardium and smooth muscle cells (Kattman et al., 2006; Moretti et al., 2006). CPCs are among the first to migrate during gastrulation, ultimately reaching bilateral regions of the anterior lateral plate mesoderm (ALPM) (Wu et al., 2008). Fate mapping studies in multiple vertebrate models have shown that CPCs arise from a fixed location in the pregastrulation embryo (reviewed in (Evans et al., 2010)). "
ABSTRACT: Myocardial progenitor development involves the migration of cells to the anterior lateral plate mesoderm (ALPM) where they are exposed to the necessary signals for heart development to proceed. Whether the arrival of cells to this location is sufficient, or whether earlier signaling events are required, for progenitor development is poorly understood. Here we demonstrate that in the absence of Aplnr signaling, cells fail to migrate to the heart-forming region of the ALPM. Our work uncovers a previously uncharacterized cell-non-autonomous function for Aplnr signaling in cardiac development. Furthermore, we show that both the single known Aplnr ligand, Apelin, and the canonical Gα(i/o) proteins that signal downstream of Aplnr are dispensable for Aplnr function in the context of myocardial progenitor development. This novel Aplnr signal can be substituted for by activation of Gata5/Smarcd3 in myocardial progenitors, suggesting a novel mechanism for Aplnr signaling in the establishment of a niche required for the proper migration/development of myocardial progenitor cells.Biology Open 03/2012; 1(3):275-85. DOI:10.1242/bio.2012380 · 2.42 Impact Factor
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- "Both these cells types have recently been targeted for delivery of pluripotent transgenes for the generation of induced pluripotent stem cells  . Cardiac progenitor cells, on the other hand, comprise of an adult stem cell population that can give rise to all the cell types that recapitulate the heart  and therefore have a strong potential to be used for cardiac repair and regeneration following myocardial infarction. In the present study, we have tested our hypothesis that PEI-based polymer hybrids can transfect primary cells at higher efficiencies than other existing non-viral methods. "
ABSTRACT: Polyethylenimine (PEI) based polymers are efficient agents for cell transfection. However, their use has been hampered due to high cell death associated with transfection thereby resulting in low efficiency of gene delivery within the cells. To circumvent the problem of cellular toxicity, metal binding peptides were linked to PEI. Eight peptide-PEI derivatives were synthesized to improve cell survival and transfection efficiency. TAT linked PEI was used as a control polymer. Peptides linked with PEI amines formed nanogels as shown by electron microscopy and atomic force microscopic measurements. Polymers were characterized by spectroscopic methods and their ability to form complexes with plasmids was tested using electrophoretic studies. These modifications improved polymer biocompatibility as well as cell survival markedly, when compared to PEI alone. A subset of the modified peptide-polymers also showed significantly higher transfection efficiency in primary human cells with respect to the widely used transfection agent, lipofectamine. Study of the underlying mechanism of the observed phenomena revealed lower levels of 'reactive oxygen species' (ROS) in the presence of the peptide-polymers when compared to PEI alone. This was further corroborated with global gene expression analysis which showed upregulation of multiple genes and pathways involved in regulating intracellular oxidative stress.Biomaterials 07/2011; 32(20):4647-58. DOI:10.1016/j.biomaterials.2011.03.016 · 8.31 Impact Factor