Epigenetic Rejuvenation of Mesenchymal Stromal Cells Derived from Induced Pluripotent Stem Cells

Frobel, Joana; Hemeda, Hatim; Lenz, Michael; Abagnale, Giulio; Joussen, Sylvia; Denecke, Bernd; Šarić, Tomo; Zenke, Martin; Wagner, Wolfgang

doi:10.1016/j.stemcr.2014.07.003

Cited by 199 publications

(259 citation statements)

References 24 publications

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“…The ability to achieve close to 100% cardiogenic differentiation significantly enhances the availability of human CMs [151]. hiPSC can potentially be used to optimize a personal therapeutic plan corresponding to patient-specific responses to drugs [152, 153]. For example, hiPSCs were derived from heart failure patients, differentiated into CMs, tested for drug responses and engrafted into a rat heart [154].…”

Section: Applications Of Cardiac Tissue Engineering In Disease Modementioning

confidence: 99%

Biomaterial based cardiac tissue engineering and its applications

Huyer¹,

Montgomery²,

Zhao³

et al. 2015

Biomed. Mater.

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Cardiovascular disease is a leading cause of death worldwide, necessitating the development of effective treatment strategies. A myocardial infarction involves the blockage of a coronary artery leading to depletion of nutrient and oxygen supply to cardiomyocytes and massive cell death in a region of the myocardium. Cardiac tissue engineering is the growth of functional cardiac tissue in vitro on biomaterial scaffolds for regenerative medicine application. This strategy relies on the optimization of the complex relationship between cell networks and biomaterial properties. In this review, we discuss important biomaterial properties for cardiac tissue engineering applications, such as elasticity, degradation, and induced host response, and their relationship to engineered cardiac cell environments. With these properties in mind, we also emphasize in vitro use of cardiac tissues for high-throughput drug screening and disease modelling.

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Section: Applications Of Cardiac Tissue Engineering In Disease Modementioning

confidence: 99%

Biomaterial based cardiac tissue engineering and its applications

Huyer¹,

Montgomery²,

Zhao³

et al. 2015

Biomed. Mater.

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show abstract

“…Cell reprogramming provides a possible route to regenerate lost stem cells, and MSC function has been reported to be mostly restored after conversion to iPSCs with subsequent redifferentiation. 28 However, even partial reprogramming based anti-aging therapies is unlikely in the near future.…”

Section: Resultsmentioning

confidence: 99%

Stem Cell Depletion by Global Disorganization of the H3K9me3 Epigenetic Marker in Aging

Mendelsohn

Larrick

2015

Rejuvenation Research

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Epigenomic change and stem cell exhaustion are two of the hallmarks of aging. Accumulation of molecular damage is thought to underlie aging, but the precise molecular composition of the damage remains controversial. That some aging phenotypes, especially those that result from impaired stem cell function, are reversible suggest that such "damage" is repairable. Evidence is accumulating that dysfunction in aging stem cells results from increasing, albeit, subtle disorganization of the epigenome over time. Zhang et al. (2015) report that decreasing levels of WRN, Werner's syndrome (WS) helicase, with increasing age results in loss of heterochromatin marks in mesenchymal stem cells (MSCs) and correlates with an increased rate of cellular senescence. Although WRN plays a role in DNA repair, WRN exerted its effects on aging via maintaining heterochromatin, evidenced by reduced levels of interacting chromatin regulators heterochromatin protein 1α (HP1α), suppressor of variegation 3-9 homolog 1 (SUV39H1), and lamina-associated polypeptide 2β (LAP2β) as well as modified histone H3K9me3. Reducing expression of chromatin modeling co-factors SUV39H1 or HP1α in wild-type MSCs recapitulates the phenotype of WRN deficiency, resulting in reduced H3K9me3 levels and increased senescence without induction of markers of DNA damage, suggesting that chromatin disorganization and not DNA damage is responsible for the pathology of WS during aging in animals. Ectopic expression of HP1α restored H3K9me3 levels and repressed senescence in WRN-deficient MSCs. That HP1α can also suppress senescence in Hutchinson-Gilford progeria syndrome (HGPS) and extend life span in flies when over-expressed suggests that HP1α and H3K9me3 play conserved roles in maintenance of cell state. H3K9me3 levels are dynamic and expected to be potentially responsive to manipulation by extrinsic factors. Recent reports that migration inhibitory factor (MIF) or periodic fasting rejuvenate old MSCs provide the opportunity to link intrinsic and extrinsic mechanisms of aging in novel and potentially medically important ways and may lead to anti-aging treatments that reorganize the epigenome to rejuvenate cells and tissues.

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“…In addition there is evidence that endoglin plays an important role in the dedifferentiation mechanism (Barbara et al 1999;Frobel et al 2014). It is noteworthy that the overexpression of endoglin markedly reduces osteogenic differentiation of MSC as detected by Alizarin Red staining (private communication),B) a marked down-regulation of Vascular Endothelial Growth Factor (VEGF).…”

Section: %°O2mentioning

confidence: 99%

The SCD – Stem Cell Differentiation ESA Project: Preparatory Work for the Spaceflight Mission

Versari

Barenghi

Loon

et al. 2015

Microgravity Sci. Technol.

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Due to spaceflight, astronauts experience serious, weightlessness-induced bone loss because of an unbalanced process of bone remodeling that involves bone marrow mesenchymal stem cells (BMSCs), as well as osteoblasts, osteocytes, and osteoclasts. The effects of microgravity on osteocells have been extensively studied, but it is only recently that consideration has been given to the role of BMSCs. Previous researches indicated that human BMSCs cultured in simulated microgravity (sim-μg) alter their proliferation and differentiation. The spaceflight opportunities for biomedical experiments are rare and suffer from a number of operative constraints that could bias the validity of the experiment itself, but remain a unique opportunity to confirm and explain the effects due to microgravity, that are only partially activated/detectable in simulated conditions. For this reason, we carefully prepared the SCD -STEM CELLS DIFFERENTIATION experiment, selected by the European Space Agency (ESA) and now on the International Space Station (ISS). Here we present the preparatory studies performed on ground to adapt the project to the spaceflight Silvia Bradamante silvia.bradamante@gmail.com constraints in terms of culture conditions, fixation and storage of human BMSCs in space aiming at satisfying the biological requirements mandatory to retrieve suitable samples for post-flight analyses. We expect to understand better the molecular mechanisms governing human BMSC growth and differentiation hoping to outline new countermeasures against astronaut bone loss.

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Epigenetic Rejuvenation of Mesenchymal Stromal Cells Derived from Induced Pluripotent Stem Cells

Cited by 199 publications

References 24 publications

Biomaterial based cardiac tissue engineering and its applications

Biomaterial based cardiac tissue engineering and its applications

Stem Cell Depletion by Global Disorganization of the H3K9me3 Epigenetic Marker in Aging

The SCD – Stem Cell Differentiation ESA Project: Preparatory Work for the Spaceflight Mission

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