Can Electrical Stimulation Prevent Recurrence of Keloid Scars? A Scoping Review.

Keloids represent a symptomatic, aberrant healing process that is difficult to treat with high recurrence rates spanning from 55% to 100% if treated excision without adjuvant therapy. Electrical stimulation (ES) has demonstrated findings that suggest it could reduce the recurrence rate of keloids after resection. Therefore, the aim of this study is to conduct a scoping review to investigate ES as an adjuvant therapy for decreasing keloid recurrence after excision.

Concise review: MicroRNAs as modulators of stem cells and angiogenesis.

MicroRNAs (miRs) are highly conserved, short noncoding RNA molecules that negatively regulate messenger RNA (mRNA) stability and/or translational efficiency. Since a given miR can control the expression of many mRNAs, their importance in governing gene expression in specific cell types including vascular cells and their progenitor cells has become increasingly clear. Understanding how the expression of miRs themselves is regulated and how miRs exert their influence on post-transcriptional gene control provides novel opportunities to dissect gene regulatory networks in clinically relevant cell types.

Profiling of transcriptional and epigenetic changes during directed endothelial differentiation of human embryonic stem cells identifies FOXA2 as a marker of early mesoderm commitment.

Introduction: Differentiation of vascular endothelial cells (ECs) in clinically relevant numbers for injection into ischaemic areas could offer therapeutic potential in the treatment of cardiovascular conditions, including myocardial infarction, peripheral vascular disease and stroke. While we and others have demonstrated successful generation of functional endothelial-like cells from human embryonic stem cells (hESCs), little is understood regarding the complex transcriptional and epigenetic changes that occur during differentiation, in particular during early commitment to a mesodermal lineage.

Methods: We performed the first gene expression microarray study of hESCs undergoing directed differentiation to ECs using a monolayer-based, feeder-free and serum-free protocol.

Integrase-deficient lentiviral vectors mediate efficient gene transfer to human vascular smooth muscle cells with minimal genotoxic risk.

We have previously shown that injury-induced neointima formation was rescued by adenoviral-Nogo-B gene delivery. Integrase-competent lentiviral vectors (ICLV) are efficient at gene delivery to vascular cells but present a risk of insertional mutagenesis. Conversely, integrase-deficient lentiviral vectors (IDLV) offer additional benefits through reduced mutagenesis risk, but this has not been evaluated in the context of vascular gene transfer.

The role of miRNA in stem cell pluripotency and commitment to the vascular endothelial lineage.

Vascular endothelial cells derived from human pluripotent stem cells have substantial potential for the development of novel vascular therapeutics and cell-based therapies for the repair of ischemic damage. To gain maximum benefit from this source of cells, a complete understanding of the changes in gene expression and how they are regulated is required. miRNAs have been demonstrated to play a critical role in controlling stem cell pluripotency and differentiation and are important for mature endothelial cell function.

Role of microRNAs 99b, 181a, and 181b in the differentiation of human embryonic stem cells to vascular endothelial cells.

MicroRNAs (miRNAs) are short noncoding RNAs, which post-transcriptionally regulate gene expression. miRNAs are transcribed as precursors and matured to active forms by a series of enzymes, including Dicer. miRNAs are important in governing cell differentiation, development, and disease.

MicroRNAs regulating cell pluripotency and vascular differentiation.

Human embryonic stem cells (hESC) offer broad potential for regenerative medicine owing to their capacity for self renewal, exponential scale up and differentiation into any cell type in the adult body. hESC have been proposed as a potentially unlimited source for the generation of transplantable, healthy, functional vascular cells for repair of ischemic tissues. To optimally harness this potential necessitates precise control over biological processes that govern maintenance, pluripotency and cell differentiation including signalling cascades, gene expression profiles and epigenetic modification.

Lentivirus-mediated reprogramming of somatic cells in the absence of transgenic transcription factors.

Retroviral vectors remain the most efficient and widely applied system for induction of pluripotency. However, mutagenic effects have been documented in both laboratory and clinical gene therapy studies, principally as a result of dysregulated host gene expression in the proximity of defined integration sites. Here, we report that cells with characteristics of pluripotent stem cells can be produced from normal human fibroblasts in the absence of reprogramming transcription factors (TFs) during lentiviral (LV) vector-mediated gene transfer.

Pluripotent stem cell differentiation into vascular cells: a novel technology with promises for vascular re(generation).

Several types of stem and progenitor cells are currently under investigation for their potential to accomplish vascular regeneration. This review focuses on embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We will discuss the technologies allowing for their derivation, culture expansion and maintenance in a pluripotent status.

Erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) blocks differentiation and maintains the expression of pluripotency markers in human embryonic stem cells.

hESCs (human embryonic stem cells) have enormous potential for use in pharmaceutical development and therapeutics; however, to realize this potential, there is a requirement for simple and reproducible cell culture methods that provide adequate numbers of cells of suitable quality. We have discovered a novel way of blocking the spontaneous differentiation of hESCs in the absence of exogenous cytokines by supplementing feeder-free conditions with EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine], an established inhibitor of ADA (adenosine deaminase) and cyclic nucleotide PDE2 (phosphodiesterase 2). hESCs maintained in feeder-free conditions with EHNA for more than ten passages showed no reduction in hESC-associated markers including NANOG, POU5F1 (POU domain class 5 transcription factor 1, also known as Oct-4) and SSEA4 (stage-specific embryonic antigen 4) compared with cells maintained in feeder-free conditions containing bFGF (basic fibroblast growth factor).

TGFβ1 attenuates expression of prolactin and IGFBP-1 in decidualized endometrial stromal cells by both SMAD-dependent and SMAD-independent pathways.

Background: Decidualization (differentiation) of the endometrial stromal cells during the secretory phase of the menstrual cycle is essential for successful implantation. Transforming Growth Factor β1 (TGFβ1) canonically propagates its actions via SMAD signalling. A role for TGFβ1 in decidualization remains to be established and published data concerning effects of TGFβ1 on markers of endometrial decidualization are inconsistent.

Identification and characterization of small-molecule ligands that maintain pluripotency of human embryonic stem cells.

hESCs (human embryonic stem cells) offer great potential for pharmaceutical research and development and, potentially, for therapeutic use. However, improvements in cell culture are urgently required to allow the scalable production of large numbers of cells that maintain pluripotency. Supplementing feeder-free conditions with either EHNA [erythro-9-(2-hydroxy-3-nonyl)adenine] or readily synthesized analogues of this compound maintains hESC pluripotency in the absence of exogenous cytokines.

Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo.

Objective: To develop an embryoid body-free directed differentiation protocol for the rapid generation of functional vascular endothelial cells derived from human embryonic stem cells (hESCs) and to assess the system for microRNA regulation and angiogenesis.

Methods And Results: The production of defined cell lineages from hESCs is a critical requirement for evaluating their potential in regenerative medicine. We developed a feeder- and serum-free protocol.

Proliferation of uterine natural killer cells is induced by human chorionic gonadotropin and mediated via the mannose receptor.

The endometrial lining of the human uterus contains a population of phenotypically distinct (CD56(bright), CD16(dim)), tissue-specific, natural killer [uterine natural killer (uNK)] cells that play a key role in the establishment of a successful pregnancy. An increase in the number of endometrial uNK cells occurs when the conceptus implants, and there is a further increase during the early stages of placentation. Here, we describe studies that have identified human chorionic gonadotrophin (hCG), a glycoprotein synthesized by the preimplantation conceptus, as a novel regulator of uNK cell proliferation.

CB1 expression is attenuated in Fallopian tube and decidua of women with ectopic pregnancy.

Background: Embryo retention in the Fallopian tube (FT) is thought to lead to ectopic pregnancy (EP), a considerable cause of morbidity. In mice, genetic/pharmacological silencing of cannabinoid receptor Cnr1, encoding CB1, causes retention of embryos in the oviduct. The role of the endocannabinoids in tubal implantation in humans is not known.

Transforming growth factor-beta1 attenuates expression of both the progesterone receptor and Dickkopf in differentiated human endometrial stromal cells.

TGFbeta1 is thought to be intimately involved in cyclic tissue remodeling and inflammatory events associated with menstruation. Menstruation is initiated by progesterone withdrawal; however, the underlying mechanisms are not well understood. In the present study, we have tested the hypothesis that locally produced TGFbeta1 may influence expression of progesterone receptor (PR) or the Wnt antagonist Dickkopf-1 (DKK) with consequential impact on regulation of menstruation.