hESC-derived immune suppressive dendritic cells induce immune tolerance of parental hESC-derived allografts.

Background: With their inherent capability of unlimited self-renewal and unique potential to differentiate into functional cells of the three germ layers, human embryonic stem cells (hESCs) hold great potential in regenerative medicine. A major challenge in the application of hESC-based cell therapy is the allogeneic immune rejection of hESC-derived allografts.

Methods: We derived dendritic cell-like cells (DCLs) from wild type and CTLA4-Ig/PD-L1 knock-in hESCs, denoted WT DCLs and CP DCLs.

Extracellular vesicles from T cells overexpress miR-146b-5p in HIV-1 infection and repress endothelial activation.

Human immunodeficiency virus type 1 (HIV-1) infection promotes a generalized activation of host responses that involves not only CD4 T cells, but also cells of the microenvironment, which are not directly infected, such as endothelial cells. The mechanisms triggering HIV-1-associated vascular alterations remain poorly understood. Extracellular vesicles (EVs), implicated in cell-to-cell communication, have been recently described as carriers of microRNAs (miRNAs).

Wild-Type p53 Promotes Cancer Metabolic Switch by Inducing PUMA-Dependent Suppression of Oxidative Phosphorylation.

The tumor suppressor p53 is somatically mutated in half of all human cancers. Paradoxically, the wild-type p53 (WTp53) is often retained in certain human cancers, such as hepatocarcinoma (HCC). We discovered a physiological and oncogenic role of WTp53 in suppressing pyruvate-driven oxidative phosphorylation by inducing PUMA.

Biogenesis of Pro-senescent Microparticles by Endothelial Colony Forming Cells from Premature Neonates is driven by SIRT1-Dependent Epigenetic Regulation of MKK6.

Senescent cells may exert detrimental effect on microenvironment through the secretion of soluble factors and the release of extracellular vesicles, such as microparticles, key actors in ageing and cardiovascular diseases. We previously reported that sirtuin-1 (SIRT1) deficiency drives accelerated senescence and dysfunction of endothelial colony-forming cells (ECFC) in PT neonates. Because preterm birth (PT) increases the risk for cardiovascular diseases during neonatal period as well as at adulthood, we hypothesized that SIRT1 deficiency could control the biogenesis of microparticles as part of a senescence-associated secretory phenotype (SASP) of PT-ECFC and investigated the related molecular mechanisms.

Extracellular Vesicles in Angiogenesis.

During the past decade, extracellular vesicles (EVs), which include apoptotic bodies, microvesicles, and exosomes, have emerged as important players in cell-to-cell communication in normal physiology and pathological conditions. EVs encapsulate and convey various bioactive molecules that are further transmitted to neighboring or more distant cells, where they induce various signaling cascades. The message delivered to the target cells is dependent on EV composition, which, in turn, is determined by the cell of origin and the surrounding microenvironment during EV biogenesis.

Antibody-Dependent NK Cell Activation Is Associated with Late Kidney Allograft Dysfunction and the Complement-Independent Alloreactive Potential of Donor-Specific Antibodies.

Although kidney transplantation remains the best treatment for end-stage renal failure, it is limited by chronic humoral aggression of the graft vasculature by donor-specific antibodies (DSAs). The complement-independent mechanisms that lead to the antibody-mediated rejection (ABMR) of kidney allografts remain poorly understood. Increasing lines of evidence have revealed the relevance of natural killer (NK) cells as innate immune effectors of antibody-dependent cellular cytotoxicity (ADCC), but few studies have investigated their alloreactive potential in the context of solid organ transplantation.

Brief Report: Immune Microenvironment Determines the Immunogenicity of Induced Pluripotent Stem Cell Derivatives.

The breakthrough of induced pluripotent stem cells (iPSCs) has raised the possibility that patient-specific iPSCs can provide autologous cells for cell therapy without the concern for immune rejection. However, the immunogenicity of iPSC-derived cells remains controversial. Using syngeneic C57BL/6 (B6) mouse transplantation model, several studies indicate that B6 iPSC-derived cells exhibit some levels of immunogenicity when transplanted into B6 mice subcutaneously.

Humanized Mice Reveal Differential Immunogenicity of Cells Derived from Autologous Induced Pluripotent Stem Cells.

The breakthrough of induced pluripotent stem cell (iPSC) technology has raised the possibility that patient-specific iPSCs may become a renewable source of autologous cells for cell therapy without the concern of immune rejection. However, the immunogenicity of autologous human iPSC (hiPSC)-derived cells is not well understood. Using a humanized mouse model (denoted Hu-mice) reconstituted with a functional human immune system, we demonstrate that most teratomas formed by autologous integration-free hiPSCs exhibit local infiltration of antigen-specific T cells and associated tissue necrosis, indicating immune rejection of certain hiPSC-derived cells.

Stemness factor Sall4 is required for DNA damage response in embryonic stem cells.

Mouse embryonic stem cells (ESCs) are genetically more stable than somatic cells, thereby preventing the passage of genomic abnormalities to their derivatives including germ cells. The underlying mechanisms, however, remain largely unclear. In this paper, we show that the stemness factor Sall4 is required for activating the critical Ataxia Telangiectasia Mutated (ATM)-dependent cellular responses to DNA double-stranded breaks (DSBs) in mouse ESCs and confer their resistance to DSB-induced cytotoxicity.

Fractalkine expression induces endothelial progenitor cell lysis by natural killer cells.

Background: Circulating CD34(+) cells, a population that includes endothelial progenitors, participate in the maintenance of endothelial integrity. Better understanding of the mechanisms that regulate their survival is crucial to improve their regenerative activity in cardiovascular and renal diseases. Chemokine-receptor cross talk is critical in regulating cell homeostasis.