Abstract:
:Liver transplantation is the only radical treatment for decompensated cirrhosis, but its use is limited owing to a shortage of donors; hence, there is an urgent need for new treatments. Previously, we developed a liver-regeneration therapy using autologous bone marrow-derived mesenchymal stem cells (BMSCs), which is under clinical investigation. Cell-cell interactions between BMSCs and macrophages (Mφs) participate in the improvement of liver function and alleviation of liver fibrosis, although the associated mechanisms have not been elucidated. Therefore, in this study, we investigated phenotypic changes in Mφs caused by interactions with BMSCs, as well as the underlying mechanisms. Co-culturing lipopolysaccharide (LPS)-stimulated murine bone marrow-derived Mφs (BMDMs) with BMSCs substantially upregulated matrix metalloproteinase 9 (Mmp9), Mmp12, and Mmp13 expression, and downregulated tumor necrosis factor alpha (Tnfα) expression. To identify humoral factors involved in phenotypic changes occurring in Mφs, microarray analysis was performed with microRNAs (miRNAs) derived from extracellular vesicles in the supernatant of co-cultured BMSCs and LPS-stimulated BMDMs. We found that miR-6769b-5p was highly expressed and that transfecting miR-6769b-5p mimic upregulated MMP9 in LPS-stimulated BMDMs and downregulated Tnfα and interleukin-1 beta (Il-1β). MiR-6769b-5p expression in BMDMs was decreased by LPS stimulation but was increased by co-culture with BMSCs. Microarray and pathway analyses of gene expression in LPS-stimulated, miR-6769b-5p-transfected BMDMs revealed changes in the eukaryotic initiation factor 2-signaling pathway and decreased the expression of activating transcription factor 4 (Atf4). LPS-stimulated BMDMs exhibited increased MMP9 expression and decreased the expression of Tnfα and Il-1β by ATF4 knockdown. These findings indicate that upregulating miR-6769b-5p in BMDMs induced a fibrolytic phenotype, where MMP9 was highly expressed and inflammatory cytokine expression was decreased by the suppression of ATF4 expression. These findings imply that regulating miR-6769b-5p or ATF4 expression in BMDMs may be helpful for treating chronic liver disease.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Nishi M,Matsumoto T,Fujisawa K,Suehiro Y,Takami T,Yamamoto N,Yamasaki T,Sakaida Idoi
10.1089/scd.2020.0123subject
Has Abstractpub_date
2020-11-15 00:00:00pages
1457-1466issue
22eissn
1547-3287issn
1557-8534journal_volume
29pub_type
杂志文章abstract::Accumulating evidence suggests that the delivery of human adipose tissue-derived stromal cells (hASCs) has great potential as regenerative therapy. This was performed to develop a method for expanding hASCs by reducing the amount of serum required. We demonstrate that hASCs were able to expand efficiently in media con...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0358
更新日期:2009-05-01 00:00:00
abstract::We compared the immunohistochemical distribution of (1) the novel chondroitin sulfate (CS) sulfation motifs 7D4, 4C3, and 3B3[-], (2) native heparan sulfate (HS) and Δ-HS "stubs" generated by heparitinase III digestion and (3) the HS-proteoglycan (PG), perlecan, in the fetal human elbow joint. Putative stem cell popul...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0054
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abstract::Cardiac stem/progenitors are being used in the clinic to treat patients with a range of cardiac pathologies. However, improvements in heart function following treatment have been reported to be variable, with some showing no response. This discrepancy in response remains unresolved. Mesenchymal stem cells (MSCs) have ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2018.0170
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abstract::On May 6th 2014, the European Court of Human Rights added yet a new element to the judicial history of stem cells as it ruled in Durisotto v. Italy [appeal n. 62804/13]. The ruling rejected a patient claim to access an unproven cell therapy-an outcome that is certainly to be welcomed. However, this ruling is a missed ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0361
更新日期:2014-12-01 00:00:00
abstract::With an incidence of ∼1:3,500 to 5,000 in male children, Duchenne muscular dystrophy (DMD) is an X-linked disorder in which progressive muscle degeneration occurs and affected boys usually die in their twenties or thirties. Cardiac involvement occurs in 90% of patients and heart failure accounts for up to 40% of death...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0135
更新日期:2013-10-15 00:00:00
abstract::Multipotent mesenchymal stromal cells (MSCs) are more and more frequently used to treat orthopedic injuries in horses. However, these cells are limited in their expandability and differentiation capacity. Recently, the first equine-induced pluripotent stem cell (iPSC) lines were reported by us [ 1 ]. In vitro differen...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0409
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abstract::White matter damage persists in hypoxic-ischemic newborns even when treated with hypothermia. We have previously shown that intraventricular delivery of human glial progenitors (GPs) at the neonatal stage is capable of replacing abnormal host glia and rescuing the lifespan of dysmyelinated mice. However, such transpla...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2018.0172
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abstract::CD41 (αIIb integrin), a specific marker for megakaryocytes and platelets, was recently shown to mark the initiation of definitive hematopoiesis in mouse embryos. However, whether embryonic CD41(+) populations have a nonhematopoietic potential remains elusive. Here, we report that the CD41(+) cells from the mouse E11.0...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0572
更新日期:2012-09-20 00:00:00
abstract::Members of the homeobox (Hox) gene family are known to mediate expansion of hematopoietic stem cells (HSCs) and progenitors. The absence of oncogenic properties promoted HOXB4 as prime candidate in the quest to expand HSCs for clinical purposes. Despite its potential to expand HSCs, studies with mutant mice showed tha...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0259
更新日期:2012-01-01 00:00:00
abstract::The development of methods to induce differentiation of human mesenchymal stem cells (hMSCs) has opened the possibility of using these cells in regenerative or reparative therapies. However, the low frequency of hMSCs in tissue means it is often necessary to expand these cells extensively in vitro. In this study, we e...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0185
更新日期:2008-10-01 00:00:00
abstract::Expression of the transcription factor Snail is required for normal vasculogenesis in the developing mouse embryo. In addition, tumors expressing Snail have been associated with a more malignant phenotype, with both increased invasive properties and angiogenesis. Although the relationship between Snail and vasculogene...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0194
更新日期:2012-01-20 00:00:00
abstract::Tumor necrosis factor-α (TNF-α) has multiple effects on proliferation and differentiation of human mesenchymal stem cells. Transforming growth factor-activated kinase-1 (TAK1) mediates the activation of nuclear factor-kappa B (NF-κB), c-Jun N-terminal kinase (JNK), and p38 pathways in response to TNF-α. However, the r...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0272
更新日期:2015-04-01 00:00:00
abstract::Reduction of estradiol production and high serum concentrations of follicular stimulating hormone (FSH) are endocrine disorders associated with premature ovarian failure. Here, we report that transplantation of ovarian-like cells differentiated from stem cells restored endogenous serum estradiol levels. Stem cells wer...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0029
更新日期:2014-07-15 00:00:00
abstract::In the seminiferous epithelium of the testis, Sertoli cells are key niche cells directing proliferation and differentiation of spermatogonial stem cells (SSCs) into spermatozoa. Sertoli cells produce glial cell line-derived neurotrophic factor (GDNF), which is essential for SSC self-renewal and progenitor expansion. W...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2016.0318
更新日期:2017-04-15 00:00:00
abstract::Phenotypic guidance of embryonic stem (ES) cell fate is paramount if these cells are to be used for tissue repair and regeneration. Our objective was to compare two different cell culture feeders and their effect on proliferation, apoptosis, and differentiation of human (h) ES cells. HSF-6 hES cells were grown in Knoc...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.0109
更新日期:2007-06-01 00:00:00
abstract::Here, we describe a focused microarray for screening rat embryonic stem cells (ESCs) and provide validation data that this array can distinguish undifferentiated rat ESCs from rat trophoblast stem (TS) cells, rat extraembryonic endoderm cells, mouse embryonic fibroblast feeder cells, and differentiated rat ESCs. Using...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0279
更新日期:2013-02-01 00:00:00
abstract::Lifelong neurogenesis in the mouse olfactory epithelium (OE) is regulated by the response of stem/progenitor cells to local signals, but embryonic and adult OE progenitors appear to be quite different--with potentially different mechanisms of regulation. A recently identified progenitor unique to embryonic OE--the nes...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0406
更新日期:2013-02-15 00:00:00
abstract::Improvement in angiogenesis using mesenchymal stem cells (MSCs) is evolving as an option in patients with vascular insufficiencies. The paracrine factors secreted by MSCs have been attributed to the angiogenic response. This study was conducted to identify the factors secreted by umbilical cord-derived MSCs (UCMSCs) t...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0184
更新日期:2015-02-15 00:00:00
abstract::Administration of human bone marrow-derived mesenchymal stem cells (BM-MSCs) significantly alleviates allergic airway inflammation. There are no studies that refer to the role of microRNAs (miRNAs) after the BM-MSCs treatment in airway allergic inflammation. We induced a mouse model of asthma and performed the transpl...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0339
更新日期:2016-06-15 00:00:00
abstract::Human embryonic stem cells (hESCs) have the potential to differentiate into many adult cell types, and they are being explored as a resource for cell replacement therapies for multiple diseases. In order to optimize in vitro differentiation protocols, it will be necessary to elucidate regulatory mechanisms that contri...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0224
更新日期:2010-06-01 00:00:00
abstract::The aim of stem cell therapy after cardiac injury is to replace damaged cardiac tissue. Human cardiac progenitor cells (CPCs) represent an interesting cell population for clinical strategies to treat cardiac disease and human CPC-specific antibodies would aid in the clinical implementation of cardiac progenitor-based ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2017.0048
更新日期:2017-11-01 00:00:00
abstract::Embryonic stem-like (ES-like) cells have now been derived from the inner cell mass (ICM) of horse embryos at the blastocyst stage. Because they have been shown to express cell-surface antigens found in both human and mouse ES cells, the present study investigated gene expression patterns in day-7 horse blastocysts fro...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0032
更新日期:2007-10-01 00:00:00
abstract::Recent studies have revealed that mesenchymal stem cells (MSCs) have a great potential in therapeutic applications. The low efficiency of MSC recruitment and homing to sites of diseased organ tissue, however, remains a major hurdle in their application for treatment of diseases. Stress is commonly associated with vari...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0243
更新日期:2015-03-01 00:00:00
abstract::In this work, we evaluated the expansion of human hematopoietic stem cells from umbilical cord blood in roller bottles. The Iscove's modified Dulbecco's medium, the Stem Pro 34-SFM medium, and the L-15 Leibovitz's medium for cultures in CO(2)-free atmosphere were assessed. At day 5 of culture, total colony forming uni...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0236
更新日期:2011-04-01 00:00:00
abstract::The placenta is a transient organ that develops upon the initiation of pregnancy and is essential for embryonic development and fetal survival. The rodent placenta consists of distinct lineages and includes cell types that are analogous to those that make up the human placenta. Trophoblast cells within the labyrinth l...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0092
更新日期:2014-12-01 00:00:00
abstract::Embryonic stem cells (ESCs) have the capacity to form all the tissues in the body and hence, directed differentiation of ESCs along specific lineages represents a means to generate therapeutically useful cell types. It has been postulated that, during in vitro differentiation, ES cells sequentially pass through simila...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2005.14.656
更新日期:2005-12-01 00:00:00
abstract::In this study, we isolated and characterized spontaneously differentiated human embryonic stem cells (SD-hESCs) found in hESC colonies in comparison to the morphologically premature ESCs in the colonies to investigate the potential role of SD-hESCs in embryogenesis. SD-hESCs were distinguished from undifferentiated hE...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0083
更新日期:2013-10-15 00:00:00
abstract::In this study we examine whether a somatic cell, once returned to a pluripotent state, gains the ability to reprogram other somatic cells. We reprogrammed mouse embryonic fibroblasts by viral induction of oct4, sox2, c-myc, and klf-4 genes. Upon fusion of the resulting iPS cells with somatic cells harboring an Oct4-GF...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0142
更新日期:2010-02-01 00:00:00
abstract::To develop biological approaches to restore vision, we developed a method of transplanting stem cell-derived retinal tissue into the subretinal space of a large-eye animal model (cat). Human embryonic stem cells (hESC) were differentiated to retinal organoids in a dish. hESC-derived retinal tissue was introduced into ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2019.0090
更新日期:2019-09-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) have received great attention due to their remarkable regenerative, angiogenic, antiapoptotic, and immunosuppressive properties. Although conventionally isolated from the bone marrow, they are known to exist in all tissues and organs, raising the question on whether they are identical cel...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0030
更新日期:2012-07-01 00:00:00