Abstract:
INTRODUCTION:Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore the molecular mechanism(s) of OFSCs regulating macrophage activity in a cytokine-inducible fashion. METHODS:LPS (100 ng/ml)-activated macrophages were treated by conditioned medium from OFSCs (OFSCs-CM) or non-contact cultured with OFSCs for 6 hours. The potency of OFSCs on macrophage proliferation and pro-inflammation ability were determined. Expression levels of pro-inflammatory cytokines in macrophages, inducible immuno-modulatory factors in OFSCs, were investigated. Deep sequencing analysis as well as interaction between microRNA (miRNA) and genes of immuno-modulators in OFSCs induced by activated macrophages was predicted by miRTar. Transfection of miRNA inhibitor into OFSCs was performed. Real-time RT-PCR and transplantation of OFSCs into mice with LPS-induced ALI confirmed the in vitro and in vivo mechanism. RESULTS:The paracrine effect of OFSCs on inhibition of macrophage pro-inflammatory cytokine release was more potent than induction of macrophage G0/G1 cell cycle arrest. OFSCs-CM suppressed LPS-induced inducible nitric oxide synthetase and the pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 alpha, and IL-1 beta expression in macrophages. Under non-contact culture, LPS-activated macrophages effectively triggered the expression of soluble immuno-modulating factors in OFSCs, i.e., IL-10, IL-1 receptor antagonist (IL-1 RA), indoleamine 2,3-dioxygenase, and soluble TNF receptor type II (sTNF RII). Under miRTar prediction, miR-671-5p was identified as a critical microRNA in regulation of multiple immune-modulating factors in OFSCs response to macrophages. The baseline level of miR-671-5p was high in OFSCs, and down-regulation of miR-671-5p upon co-culture with activated macrophages was observed. MiR-671-5p inhibitor transfection into OFSCs selectively enhanced the IL-1 RA and sTNF RII expressions. In addition, inhibition of miR-671-5p in OFSCs enhanced the anti-inflammatory ability against LPS-induced ALI. CONCLUSION:The paracrine effect of OFSCs inhibits the pro-inflammatory ability and proliferation of macrophages. The immune-modulation capacity of OFSCs can be triggered by activated macrophages, and down-regulation of miR-671-5p enhances OFSC immuno-modulation ability by up-regulating IL-1 RA and sTNF RII expression.
journal_name
Stem Cell Res Therjournal_title
Stem cell research & therapyauthors
Lien GS,Liu JF,Chien MH,Hsu WT,Chang TH,Ku CC,Ji AT,Tan P,Hsieh TL,Lee LM,Ho JHdoi
10.1186/scrt486subject
Has Abstractpub_date
2014-08-13 00:00:00pages
97issue
4issn
1757-6512pii
scrt486journal_volume
5pub_type
杂志文章abstract:INTRODUCTION:Osteopontin (OPN) is a phosphoglycoprotein with important roles in tissue homeostasis, wound healing, immune regulation, and stress responses. It is expressed constitutively in the brain and upregulated during neuroinflammatory responses; for example, after focal cerebral ischemia. To date, its effects on ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0098-x
更新日期:2015-05-22 00:00:00
abstract:BACKGROUND:Exosomes are nanovesicles (30-120 nm) of endosomal origin. These exosomes contain various functional proteins and RNAs that could be used for therapeutic purposes. Currently, having a standard method for exosome isolation retaining its biological properties with increased yield and purity is a major challeng...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0923-0
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abstract:BACKGROUND:Optimal cell type as cell-based therapies for heart failure (HF) remains unclear. We sought to compare the safety and efficacy of direct intramyocardial transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1183-3
更新日期:2019-03-07 00:00:00
abstract::The proteasome is a multi-enzyme complex responsible for orchestrating protein quality control by degrading misfolded, damaged, abnormal and foreign proteins. Studies related to the association of the proteasomal system in the preservation of self-renewal in both human and mouse pluripotent cells are sparse, and there...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/scrt413
更新日期:2014-02-18 00:00:00
abstract::On 23 May 2013, the Italian health minister decided to endorse a law regarding controversial stem cell-based therapies in 32 young terminally ill patients, shocking many scientists. According to the international scientific community, these therapies could be dangerous because they were not rigorously tested in humans...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/scrt333
更新日期:2013-10-11 00:00:00
abstract:BACKGROUND:Spinal metastasis is a major challenge in patients with advanced lung cancer, but the mechanisms in the organotropism of metastasis are still unclear. Adipose-derived mesenchymal stem cells (ADSCs) exhibit cancer-promoting properties that influence the tumour microenvironment; however, there is no research o...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1280-3
更新日期:2019-06-13 00:00:00
abstract:BACKGROUND:Bone marrow-derived cell therapy has been used to treat acute myocardial infarction. However, the therapeutic efficacy of this approach remains controversial. Here, we performed a systematic review and meta-analysis to evaluate short-term and long-term effectiveness of bone marrow-derived therapy. METHODS:W...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,meta分析
doi:10.1186/s13287-016-0415-z
更新日期:2016-10-20 00:00:00
abstract:BACKGROUND:The therapeutic effect of mesenchymal stem cells (MSCs) from human adipose tissue on renal interstitial fibrosis has been demonstrated by several groups. However, the way to enhance the renoprotective effect of adipose-derived mesenchymal stem cells (AMSCs) and the possible mechanisms are still unclear. The ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-02049-z
更新日期:2021-01-07 00:00:00
abstract:BACKGROUND:Mesenchymal stromal cells (MSCs) have been largely investigated, in the past decade, as potential therapeutic strategies for various acute and chronic pathological conditions. MSCs isolated from different sources, such as bone marrow (BM), umbilical cord tissue (UCT) and adipose tissue (AT), share many biolo...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0383-3
更新日期:2016-08-25 00:00:00
abstract:INTRODUCTION:Fetal bovine serum (FBS) is an animal product used as a medium supplement. The animal origin of FBS is a concern if cultured stem cells are to be utilized for human cell therapy. Therefore, a substitute for FBS is desirable. In this study, an industrial, xeno-free, pharmaceutical-grade supplement for cell ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0016-2
更新日期:2015-03-13 00:00:00
abstract:BACKGROUND:Adult full-thickness cutaneous wound repair suffers from an imbalanced immune response, leading to nonfunctional reconstructed tissue and fibrosis. Although various treatments have been reported, the immune-mediated tissue regeneration driven by biomaterial offers an attractive regenerative strategy for dama...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0768-6
更新日期:2018-01-31 00:00:00
abstract:BACKGROUND:Vocal fold (VF) scarring, caused by surgery or inflammation, often results in severe voice problems or aphonia. Effective lasting treatment is lacking. Previous in vitro and in vivo animal studies reported positive effects on VF scar resolution with mesenchymal stromal cell (MSC) implantation. The principal ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01632-8
更新日期:2020-03-20 00:00:00
abstract:BACKGROUND:Bone marrow mesenchymal stem cells (BMSCs) exhibit the capacity to self-renew and differentiate into multi-lineage cell types, including osteoblasts, which are crucial regulators of fracture healing. Thus, this study aims to investigate the effect of microRNA (miR)-22-3p from BMSC-derived EVs on osteogenic d...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01707-6
更新日期:2020-06-10 00:00:00
abstract:INTRODUCTION:Studies have demonstrated that mesenchymal stromal cells (MSCs) could reverse acute and chronic kidney injury by a paracrine or endocrine mechanism, and microvesicles (MVs) have been regarded as a crucial means of intercellular communication. In the current study, we focused on the therapeutic effects of h...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt428
更新日期:2014-03-19 00:00:00
abstract:INTRODUCTION:The therapeutic potential of acyclic retinoid (ACR), a synthetic retinoid, has been confirmed in experimental and clinical studies. Therapeutic targets include precancerous and cancer stem cells. As ACR is also involved in developmental processes, its effect on normal hepatic stem cells (HpSCs) should be i...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0046-9
更新日期:2015-03-26 00:00:00
abstract:INTRODUCTION:Stem cell therapy has emerged as potential therapeutic strategy for damaged heart muscles. Umbilical cord blood (UCB) cells are the most prevalent stem cell source available, yet have not been fully tested in cardiac regeneration. Herein, studies were performed to evaluate the cardiovascular safety and ben...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0044-y
更新日期:2015-03-26 00:00:00
abstract:BACKGROUND:miRNA expression profiles in ectopic endometrium (EC) serving as pathophysiologic genetic fingerprints contribute to determining endometriosis progression; however, the underlying molecular mechanisms remain unknown. METHODS:miRNA microarray analysis was used to determine the expression profiling of EC fres...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1388-5
更新日期:2019-09-23 00:00:00
abstract:BACKGROUND:Mesenchymal stromal cells (MSCs) are considered potential candidates that hold great promise in the treatment of immune-related diseases. For therapeutic applications, it is necessary to isolate and expand MSCs with procedures complying with good manufacturing practice (GMP). Recent studies reported the use ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1175-3
更新日期:2019-03-07 00:00:00
abstract:INTRODUCTION:Increased levels of angiotensin II (Ang II) and activity of Ang II receptor type 1 (AT1R) elicit detrimental effects in cardiovascular disease. However, the role of Ang II receptor type 2 (AT2R) remains poorly defined. Mesenchymal stem cells (MSCs) replenish and repair endothelial cells in the cardiovascul...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt538
更新日期:2015-01-06 00:00:00
abstract:BACKGROUND:Graft-versus-host disease (GvHD) is the main life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT). Thirty to 80% of GvHD patients do not respond to first-line treatment and a second-line treatment is not universally established. Based on their immunomodulatory properties...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01592-z
更新日期:2020-02-18 00:00:00
abstract:BACKGROUND:Mesenchymal stromal/stem cells derived from human umbilical cord (UC-MSCs) uniquely combine properties of embryonic and postnatal MSCs and may be the most acceptable, safe, and effective source for allogeneic cell therapy e.g. for therapeutic angiogenesis. In this report we describe pro-angiogenic properties...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0305-4
更新日期:2016-03-22 00:00:00
abstract:BACKGROUND:Transplantation of endothelial progenitor cells (EPCs)/endothelial cells (ECs) has been used for the treatment of ischemic diseases and hemophilia A, due to their great capacity for producing factor VIII and for repairing vascular damage. We established an effective approach to stimulate the expansion and di...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0482-9
更新日期:2017-02-07 00:00:00
abstract:INTRODUCTION:Octamer-binding transcription factor 4 (Oct4) is a master regulator of early mammalian development. Its expression begins from the oocyte stage, becomes restricted to the inner cell mass of the blastocyst and eventually remains only in primordial germ cells. Unearthing the interactions of Oct4 would provid...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt67
更新日期:2011-05-13 00:00:00
abstract:BACKGROUND:To investigate the therapeutic effect of intercellular adhesion molecule (ICAM)-1-modified mesenchymal stem cells (MSCs) in a mouse model of inflammatory bowel disease (IBD) induced by dextran sulfate sodium. METHODS:Primary MSCs and ICAM-1-overexpressing MSCs (C3 cells) were generated in vitro. The IBD mou...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1384-9
更新日期:2019-08-23 00:00:00
abstract:BACKGROUND:Neonatal hypoxia-ischemia induces massive brain damage during the perinatal period, resulting in long-term consequences to central nervous system structural and functional maturation. Although neural progenitor cells (NPCs) migrate through the parenchyma and home in to injury sites in the rodent brain, the m...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0474-9
更新日期:2017-02-07 00:00:00
abstract:BACKGROUND:Degeneration of smooth muscles in sphincters can cause debilitating diseases such as fecal incontinence. Skeletal muscle-derived cells have been effectively used in clinics for the regeneration of the skeletal muscle sphincters, such as the external anal or urinary sphincter. However, little is known about t...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01749-w
更新日期:2020-06-12 00:00:00
abstract:BACKGROUND:Stem cells from human exfoliated deciduous teeth (SHED) have recently attracted attention as novel multipotential stem cell sources. However, their application is limited due to in vitro replicative senescence. Ectopic expression of telomerase reverse transcriptase (TERT) is a promising strategy for overcomi...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0309-0
更新日期:2016-04-04 00:00:00
abstract:BACKGROUND:Clinical use of mesenchymal stem cells (MSCs) requires a uniform cell population, and their harvesting is invasive and produces a limited number of cells. Human embryonic stem cell-derived MSCs (hESC-MSCs) can differentiate into three germ layers and possess immunosuppressive effects in vitro. Anticancer tre...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01769-6
更新日期:2020-06-26 00:00:00
abstract::Extracellular vesicles (EVs) contain proteins, microRNAs, mRNAs, long non-coding RNAs, and phospholipids, and are a novel mechanism of intercellular communication. It has been proposed that the immunomodulatory and regenerative effects of mesenchymal stem/stromal cells (MSCs) are mainly mediated by soluble paracrine f...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13287-019-1484-6
更新日期:2019-11-28 00:00:00
abstract:INTRODUCTION:Mesenchymal stem cells (MSCs) are multipotent and have been derived from various tissues. Although MSCs share many basic features, they often display subtle tissue specific differences. We previously demonstrated that bone marrow (BM) MSCs frequently become polyploid in culture. This tendency was mediated ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt529
更新日期:2014-12-17 00:00:00