The hsa-miR-5787 represses cellular growth by targeting eukaryotic translation initiation factor 5 (eIF5) in fibroblasts

MicroRNAs (miRNAs) are small non-coding RNAs that regulate diverse biological processes. We cloned novel small RNA from human mesenchymal stem cells (hMSCs) and termed microRNA-5787 (hsa-miR-5787) that met the criteria for a miRNA. The level of miR-5787 was elevated in senescent fibroblasts. Based on the target prediction algorithm and results that were obtained, we find that eukaryotic translation initiation factor 5 (eIF5) is a target of miR-5787. Similar to the over-expression of miR-5787, we showed that repression of eIF5 in fibroblasts negatively affected cell growth. Therefore, we propose that the miR-5787 represses cell growth, in part, by targeting eIF5.     

人嗅觉黏膜间充质干细胞来源的外泌体促进内皮细胞的血管生成

外泌体作为是细胞旁分泌的重要介质,在促血管形成方面有重要作用。在我们前期研究中,已经成功从嗅黏膜间充质干细胞（olfactory mucosa mesenchymal stem cells,OM-MSCs）分离、鉴定了其外泌体,然而,OM-MSCs源外泌体对血管生成的影响尚不清楚。本研究旨在探讨OM-MSCs来源外泌体对内皮细胞血管生成能力的影响。采用PKH67 荧光标记OM-MSCs源外泌体,与人脑微血管内皮细胞（human brain microvessel endothelial cells, HBMECs) 共培养,观察 OM-MSCs外泌体能否进入 HBMECs。采用CCK-8法、Transwell 迁移实验和小管实验,观察 OM-MSCs外泌体对 HBMECs增殖、迁移及管状结构形成的影响。采用基质胶塞实验及CD31免疫荧光,观察OM-MSCs外泌体在体内对血管生成的影响。上述研究均以等量 PBS 作为对照。结果提示,OM-MSCs外泌体可被HBMECs 摄取。CCK-8 法检测显示,在处理1、2、3、4、5 d各时间点,实验组细胞增殖均优于对照组（1.32±0.14 vs. 0.98±0.04, 1.36±0.14 vs.1.04±0.06, 1.75±0.18 vs.1.33±0.11, 2.16±0.11 vs.1.50±0.19, 2.71±0.11 vs. 1.81±0.20, P<0.01）。Transwell 实验结果显示,实验组跨膜迁移细胞吸光度值较对照组显著增多（1.12±0.05 vs.0.02±0.02, P<0.05）。在体外小管实验中,从节点、交叉点、网眼数、血管分支数和总长度5个方面,实验组均高于空白对照组（374.33±127.74 vs. 193.33±44.79, 104.56±33.07 vs. 54.33±11.65, 20.11±11.20 vs. 7.56±3.64, 81.67±19.07 vs. 57.00±13.02, 11466.22±2781.03 vs. 8544.00±1848.61, P<0.05）;在体内实验中,实验组成血管及CD31阳性率（%）亦显著高于对照组（85.00±5.57 vs.8.00±2.08, P<0.05）。本研究表明：OM-MSCs外泌体可促进 HBMECs 增殖、迁移及管样结构形成,提示OM-MSCs外泌体可促进血管新生。     

Mesenchymal stromal cells (MSCs) for neurodegenerative disease: A promising frontier

Neurodegenerative disorders are a variety of diseases including Alzheimer's (AD), Parkinson's (PD), and Huntington's diseases (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS) along with some other less common diseases generally described by the advanced deterioration of central or peripheral nervous system, structurally or functionally. In the last two decades, mesenchymal stromal cells (MSCs) due to their unique assets encompassing self-renewal, multipotency and accessibility in association with low ethical concern open new frontiers in the context of neurodegenerative diseases therapy. Interestingly, MSCs can be differentiated into endodermal and ectodermal lineages (e.g., neurons, oligodendrocyte, and astrocyte), and thus could be employed to advance cell-based therapeutic strategy. Additionally, as inflammation ordinarily ensues as a local response provoked by microglia in the neurodegenerative diseases, MSCs therapy because of their pronounced immunomodulatory properties is noticed as a rational approach for their treatment. Recently, varied types of studies have been mostly carried out in vitro and rodent models using MSCs upon their procurement from various sources and expansion. The promising results of the studies in rodent models have motivated researchers to design and perform several clinical trials, with a speedily rising number. In the current review, we aim to deliver a brief overview of MSCs sources, expansion strategies, and their immunosuppressive characteristics and discuss credible functional mechanisms exerted by MSCs to treat neurodegenerative disorders, covering AD, PD, ALS, MS, and HD.     

Expression and functional role of formyl peptide receptor in human bone marrow-derived mesenchymal stem cells

We investigated the expression of formyl peptide receptor (FPR) and its functional role in human bone marrow-derived mesenchymal stem cells (MSCs). We analyzed the expression of FPR by using ligand-binding assay with radio-labeled N-formyl-met-leu-phe (fMLF), and found that MSCs express FPR. FMLF stimulated intracellular calcium increase, mitogen-activated protein kinases activation, and Akt activation, which were mediated by G(i) proteins. MSCs were chemotactically migrated to fMLF. FMLF-induced MSC chemotaxis was also completely inhibited by pertussis toxin, LY294002, and PD98059, indicating the role of G(i) proteins, phosphoinositide 3-kinase, and extracellular signal regulated protein kinase. N-terminal fragment of annexin-1, Anx-1(2-26), an endogenous agonist for FPR, also induced chemotactic migration of MSCs. Thus MSCs express functional FPR, suggesting a new (patho)physiological role of FPR and its ligands in regulating MSC trafficking during induction of injured tissue repair.     

Mechanosensitive channels and their functions in stem cell differentiation

Stem cells continuously perceive and respond to various environmental signals during development, tissue homeostasis, and pathological conditions. Mechanical force, one of the fundamental signals in the physical world, plays a vital role in the regulation of multiple functions of stem cells. The importance of cell adhesion to the extracellular matrix (ECM), cell-cell junctions, and a mechanoresponsive cell cytoskeleton has been under intensive study in the fields of stem cell biology and mechanobiology. However, the involvement of mechanosensitive (MS) ion channels in the mechanical regulation of stem cell activity has just begun to be realized. Here, we review the diversity and importance of mechanosensitive channels (MSCs), and discuss recently discovered functions of MSCs in stem cell regulation, especially in the determination of cell fate.     

How to influence the mesenchymal stem cells fate? Emerging role of ectoenzymes metabolizing nucleotides

Extracellular purines, principally adenosine triphosphate and adenosine, are among the oldest evolutionary and widespread chemical messengers. The integrative view of purinergic signaling as a multistage coordinated cascade involves the participation of nucleotides/nucleosides, their receptors, enzymes metabolizing extracellular nucleosides and nucleotides as well as several membrane transporters taking part in the release and/or uptake of these molecules. In view of the emerging data, it is evident and widely accepted that an extensive network of diverse enzymatic activities exists in the extracellular space. The enzymes regulate the availability of nucleotide and adenosine receptor agonists, and consequently, the course of signaling events. The current data indicate that mesenchymal stem cells (MSCs) and cells induced to differentiate exhibit different sensitivity to purinergic ligands as well as a distinct activity and expression profiles of ectonucleotidases than mature cells. In the proposed review, we postulate for a critical role of these enzymatic players which, by orchestrating a fine-tune regulation of nucleotides concentrations, are integrally involved in modulation and diversification of purinergic signals. This specific hallmark of the MSC purinome should be linked with cell-specific biological potential and capacity for tissue regeneration. We anticipate this publication to be a starting point for scientific discussion and novel approach to the in vitro and in vivo regulation of the MSC properties.     

Direct contacts with colon cancer cells regulate the differentiation of bone marrow mesenchymal stem cells into tumor associated fibroblasts

Tumor–stroma interactions are referred to as essential events in tumor progression. There has been growing attention that bone marrow-derived mesenchymal stem cells (BMSCs) can travel to tumor stroma, where they differentiate into tumor-associated fibroblast (TAF)-like cells, a predominant tumor-promoting stromal cell. However, little is definitively known about the contributors for this transition. Here, using an in vitro direct co-culture model of colon cancer cells and BMSCs, we identify that colon cancer cells can induce adjoining BMSCs to exhibit the typical characteristic of TAFs, with increased expression of α-smooth muscle actin (α-SMA). Importantly, the present data also reveals that activated Notch signaling mediates transformation of BMSCs to TAFs through the downstream TGF-β/Smad signaling pathway.