Loss of miR-132/212 Has No Long-Term Beneficial Effect on Cardiac Function After Permanent Coronary Occlusion in Mice.

Myocardial infarction (MI) is caused by occlusion of the coronary artery and induces ischemia in the myocardium and eventually a massive loss in cardiomyocytes. Studies have shown many factors or treatments that can affect the healing and remodeling of the heart upon infarction, leading to better cardiac performance and clinical outcome. Previously, miR-132/212 has been shown to play an important role in arteriogenesis in a mouse model of hindlimb ischemia and in the regulation of cardiac contractility in hypertrophic cardiomyopathy in mice.

MMISH: Multicolor microRNA hybridization for paraffin embedded samples.

To understand and assess the roles of miRNAs, visualization of the expression patterns of specific miRNAs is needed at the cellular level in a wide variety of different tissue types. Although miRNA hybridization techniques have been greatly improved in recent years, they remain difficult to routinely perform due to the complexity of the procedure. In addition, as it is crucial to define which tissues or cells are expressing a particular miRNA in order to elucidate the biological function of the miRNA, incorporation of additional stainings for different cellular markers is necessary.

Exosomes from Cardiomyocyte Progenitor Cells and Mesenchymal Stem Cells Stimulate Angiogenesis Via EMMPRIN.

To date, cellular transplantation therapy has not yet fulfilled its high expectations for cardiac repair. A major limiting factor is lack of long-term engraftment of the transplanted cells. Interestingly, transplanted cells can positively affect their environment via secreted paracrine factors, among which are extracellular vesicles, including exosomes: small bi-lipid-layered vesicles containing proteins, mRNAs, and miRNAs.

Circulating Extracellular Vesicles Contain miRNAs and are Released as Early Biomarkers for Cardiac Injury.

Plasma-circulating microRNAs have been implicated as novel early biomarkers for myocardial infarction (MI) due to their high specificity for cardiac injury. For swift clinical translation of this potential biomarker, it is important to understand their temporal and spatial characteristics upon MI. Therefore, we studied the temporal release, potential source, and transportation of circulating miRNAs in different models of ischemia reperfusion (I/R) injury.

Increased local delivery of antagomir therapeutics to the rodent myocardium using ultrasound and microbubbles.

Recent developments in microRNA (miRNA) research have identified these as important mediators in the pathophysiological response upon myocardial infarction (MI). Specific miRNAs can inhibit the translation of entire groups of mRNAs, which are involved in specific processes in the pathophysiology after MI, e.g.

MicroRNA-1 enhances the angiogenic differentiation of human cardiomyocyte progenitor cells.

Instigated by the discovery of adult cardiac progenitor cells, cell replacement therapy has become a promising option for myocardial repair in the past decade. We have previously shown that human-derived cardiomyocyte progenitor cells (hCMPCs) can differentiate into cardiomyocyte-, endothelial-, and smooth muscle-like cells in vitro, and in vivo after transplantation in a mouse model of myocardial infarction, resulting in preservation of cardiac function. However, to allow successful repopulation of the injured myocardium, it is of key importance to restore myocardial perfusion by the formation of new vasculature.

MiR-155 inhibits cell migration of human cardiomyocyte progenitor cells (hCMPCs) via targeting of MMP-16.

Undesired cell migration after targeted cell transplantation potentially limits beneficial effects for cardiac regeneration. MicroRNAs are known to be involved in several cellular processes, including cell migration. Here, we attempt to reduce human cardiomyocyte progenitor cell (hCMPC) migration via increasing microRNA-155 (miR-155) levels, and investigate the underlying mechanism.

Cardiac tissue engineering using tissue printing technology and human cardiac progenitor cells.

Tissue engineering is emerging as a potential therapeutic approach to overcome limitations of cell therapy, like cell retention and survival, as well as to mechanically support the ventricular wall and thereby prevent dilation. Tissue printing technology (TP) offers the possibility to deliver, in a defined and organized manner, scaffolding materials and living cells. The aim of our study was to evaluate the combination of TP, human cardiac-derived cardiomyocyte progenitor cells (hCMPCs) and biomaterials to obtain a construct with cardiogenic potential for in vitro use or in vivo application.

MicroRNA-155 prevents necrotic cell death in human cardiomyocyte progenitor cells via targeting RIP1.

To improve regeneration of the injured myocardium, cardiomyocyte progenitor cells (CMPCs) have been put forward as a potential cell source for transplantation therapy. Although cell transplantation therapy displayed promising results, many issues need to be addressed before fully appreciating their impact. One of the hurdles is poor graft-cell survival upon injection, thereby limiting potential beneficial effects.

Foetal and adult cardiomyocyte progenitor cells have different developmental potential.

In the past years, cardiovascular progenitor cells have been isolated from the human heart and characterized. Up to date, no studies have been reported in which the developmental potential of foetal and adult cardiovascular progenitors was tested simultaneously. However, intrinsic differences will likely affect interpretations regarding progenitor cell potential and application for regenerative medicine.

MicroRNA-1 and -499 regulate differentiation and proliferation in human-derived cardiomyocyte progenitor cells.

Objective: To improve regeneration of the injured myocardium, it is necessary to enhance the intrinsic capacity of the heart to regenerate itself and/or replace the damaged tissue by cell transplantation. Cardiomyocyte progenitor cells (CMPCs) are a promising cell population, easily expanded and efficiently differentiated into beating cardiomyocytes. Recently, several studies have demonstrated that microRNAs (miRNAs) are important for stem cell maintenance and differentiation via translational repression.

Human cardiomyocyte progenitor cell-derived cardiomyocytes display a maturated electrical phenotype.

Cardiomyocyte progenitor cells (CMPCs) can be isolated from the human heart and differentiated into cardiomyocytes in vitro. A comprehensive assessment of their electrical phenotype upon differentiation is essential to predict potential future applications of this cell source. CMPCs isolated from human fetal heart were differentiated in vitro and examined using immunohistochemistry, Western blotting, RT-PCR, voltage clamp and current clamp techniques.

A new in vitro model for stem cell differentiation and interaction.

Development involves an interplay between various cell types from their birth to their disappearance by differentiation, migration, or death. Analyzing these interactions provides insights into their roles during the formation of a new organism. As a study tool for these interactions, we have created a model based on embryoid bodies (EBs) generated from mouse embryonic stem (mES) cells, which can be used to visualize the differentiation of mES cells into specific cell types while at the same time allowing controlled removal of this same cell population using an enzyme-prodrug approach.

Human cardiomyocyte progenitor cells differentiate into functional mature cardiomyocytes: an in vitro model for studying human cardiac physiology and pathophysiology.

To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is very low. Other methods to differentiate progenitor cells into beating cardiomyocytes rely on coculturing with rat neonatal cardiomyocytes, making it difficult to study human cardiomyocyte differentiation and (patho)physiology.

Juglone inactivates cysteine-rich proteins required for progression through mitosis.

The parvulin peptidyl-prolyl isomerase Pin1 catalyzes cis-trans isomerization of p(S/T)-P bonds and might alter conformation and function of client proteins. Since the trans conformation of p(S/T)-P bonds is preferred by protein phosphatase 2A (PP2A), Pin1 may facilitate PP2A-mediated dephosphorylation. Juglone irreversibly inhibits parvulins and is often used to study the function of Pin1 in vivo.

TGF-beta1 induces efficient differentiation of human cardiomyocyte progenitor cells into functional cardiomyocytes in vitro.

The adult mammalian heart has limited regenerative capacity and was generally considered to contain no dividing cells. Recently, however, a resident population of progenitor cells has been identified, which could represent a new source of cardiomyocytes. Here, we describe the efficient isolation and propagation of human cardiomyocyte progenitor cells (hCMPCs) from fetal heart and patient biopsies.

Munc13-4 is an effector of rab27a and controls secretion of lysosomes in hematopoietic cells.

Griscelli syndrome type 2 (GS2) is a genetic disorder in which patients exhibit life-threatening defects of cytotoxic T lymphocytes (CTLs) whose lytic granules fail to dock on the plasma membrane and therefore do not release their contents. The disease is caused by the absence of functional rab27a, but how rab27a controls secretion of lytic granule contents remains elusive. Mutations in Munc13-4 cause familial hemophagocytic lymphohistiocytosis subtype 3 (FHL3), a disease phenotypically related to GS2.