Abstract:
BACKGROUND:Liver organoid technology holds great promises to be used in large-scale population-based drug screening and in future regenerative medicine strategies. Recently, some studies reported robust protocols for generating isogenic liver organoids using liver parenchymal and non-parenchymal cells derived from induced pluripotent stem cells (iPS) or using isogenic adult primary non-parenchymal cells. However, the use of whole iPS-derived cells could represent great challenges for a translational perspective. METHODS:Here, we evaluated the influence of isogenic versus heterogenic non-parenchymal cells, using iPS-derived or adult primary cell lines, in the liver organoid development. We tested four groups comprised of all different combinations of non-parenchymal cells for the liver functionality in vitro. Gene expression and protein secretion of important hepatic function markers were evaluated. Additionally, liver development-associated signaling pathways were tested. Finally, organoid label-free proteomic analysis and non-parenchymal cell secretome were performed in all groups at day 12. RESULTS:We show that liver organoids generated using primary mesenchymal stromal cells and iPS-derived endothelial cells expressed and produced significantly more albumin and showed increased expression of CYP1A1, CYP1A2, and TDO2 while presented reduced TGF-β and Wnt signaling activity. Proteomics analysis revealed that major shifts in protein expression induced by this specific combination of non-parenchymal cells are related to integrin profile and TGF-β/Wnt signaling activity. CONCLUSION:Aiming the translation of this technology bench-to-bedside, this work highlights the role of important developmental pathways that are modulated by non-parenchymal cells enhancing the liver organoid maturation.
journal_name
Stem Cell Res Therjournal_title
Stem cell research & therapyauthors
Goulart E,de Caires-Junior LC,Telles-Silva KA,Araujo BHS,Kobayashi GS,Musso CM,Assoni AF,Oliveira D,Caldini E,Gerstenhaber JA,Raia S,Lelkes PI,Zatz Mdoi
10.1186/s13287-019-1367-xsubject
Has Abstractpub_date
2019-08-15 00:00:00pages
258issue
1issn
1757-6512pii
10.1186/s13287-019-1367-xjournal_volume
10pub_type
杂志文章abstract::Cognitive deficit has been identified in one third of patients affected by Duchenne Muscular Dystrophy, primarily attributed to loss of the short Dp71 dystrophin, the major brain dystrophin isoform. In this study, we investigated for the first time the Dp71 and Dp71-associated proteins cellular localization and expres...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-1125-5
更新日期:2019-01-15 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:BACKGROUND:The Activin A and bone morphogenetic protein (BMP) pathways are critical regulators of the immune system and of bone formation. Inappropriate activation of these pathways, as in conditions of congenital heterotopic ossification, are thought to activate an osteogenic program in endothelial cells. However, if ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0372-6
更新日期:2016-08-17 00:00:00
abstract:BACKGROUND:One of the most severe complications of the current COVID-19 pandemic is acute respiratory distress syndrome (ARDS). ARDS is caused by increased amounts of pro-inflammatory cytokines, leading to lung damage and loss of lung function. There are currently no effective therapies for combatting ARDS. Mesenchymal...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-021-02143-w
更新日期:2021-01-19 00:00:00
abstract:BACKGROUND:Bone marrow mesenchymal stem cells (BMMSCs) are suitable cell sources for dental pulp regeneration, but the mechanism of BMMSCs differentiation into odontogenic lineage remains unknown. The aim of the present study was to reveal the role of magnesium transporter protein 1 (MagT1) and MAPK pathways in the odo...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1148-6
更新日期:2019-01-31 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:BACKGROUND:We aimed to generate a bioengineered multi-lamellar human corneal stroma tissue in vitro by differentiating periodontal ligament stem cells (PDLSCs) towards keratocytes on an aligned silk membrane. METHODS:Human PDLSCs were isolated and identified. The neuropeptide substance P (SP) was added in keratocyte d...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0715-y
更新日期:2017-11-13 00:00:00
abstract::Damage of mitochondria in the initial period of tissue injury aggravates the severity of injury. Restoration of mitochondria dysfunction and mitochondrial-based therapeutics represent a potentially effective therapeutic strategy. Recently, mitochondrial transfer from stem cells has been demonstrated to play a signific...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13287-018-0832-2
更新日期:2018-04-13 00:00:00
abstract:INTRODUCTION:Despite attempts to prevent brain injury during the hyperacute phase of stroke, most sufferers end up with significant neuronal loss and functional deficits. The use of cell-based therapies to recover the injured brain offers new hope. In the current study, we employed human neural stem cells (hNSCs) isola...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0175-1
更新日期:2015-09-29 00:00:00
abstract:INTRODUCTION:Fallopian tube, which is normally discarded in surgical procedures, has proven to be a source of mesenchymal stem cells (MSCs) with increasing evidence. However, fallopian tube mucosa, which can be acquired via non-invasive procedures, is a previously unknown source of MSCs. In the present study, we explor...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0094-1
更新日期:2015-05-21 00:00:00
abstract:BACKGROUND:Senescent cells are undesirable in cell therapy products due to reduced therapeutic activity and risk of aberrant cellular effects, and methods for assessing senescence are needed. Early-passage mesenchymal stromal cells (MSCs) are known to be small and spindle-shaped but become enlarged upon cell aging. Ind...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0740-x
更新日期:2018-01-10 00:00:00
abstract:INTRODUCTION:Stem cells have been evaluated as a potential therapeutic approach for several neurological disorders of the central and peripheral nervous system as well as for traumatic brain and spinal cord injury. Currently, the lack of a reliable and safe method to accurately and non-invasively locate the site of imp...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0129-7
更新日期:2015-07-21 00:00:00
abstract:BACKGROUND:Adipose tissue-derived stem cells are considered to be a promising source in the field of cell therapy and regenerative medicine. In addition to direct cell replacement using adipose tissue or purified stem cells, intercellular molecule exchange by the adipose tissue complex, a vast array of bioactive secret...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0956-4
更新日期:2018-08-09 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:Hertwig's epithelial root sheath (HERS) is important in guiding tooth root formation by differentiating into cementoblasts through epithelial-mesenchymal transition (EMT) and inducing odontoblastic differentiation of dental papilla through epithelial-mesenchymal interaction (EMI) during the tooth root develo...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-1106-8
更新日期:2019-01-03 00:00:00
abstract:BACKGROUND:Apelin plays a key beneficial role in energy metabolism by increasing glucose uptake and insulin sensitivity; however, apelin has a short half-life because it is rapidly cleared from the circulation limiting its therapeutic benefit. The aim of this study is to create a new approach to treat type 2 diabetes b...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-1084-x
更新日期:2018-12-07 00:00:00
abstract:BACKGROUND:Silicon-modified biomaterials have been extensively studied in bone tissue engineering. In recent years, the toxicity of silicon-doped biomaterials has gradually attracted attention but requires further elucidation. This study was designed to explore whether high-dose silicate can induce a cytotoxicity effec...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1441-4
更新日期:2019-11-27 00:00:00
abstract:BACKGROUND:Induced pluripotent stem cells (iPSCs) exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine. Thus, inducing iPSCs toward a specific differentiation direction is an important scientific question. Traditionally, iPSCs have bee...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01606-w
更新日期:2020-02-21 00:00:00
abstract:BACKGROUND:Periodontal ligament stromal cells (PDLSCs) are ideal cell sources for periodontal tissue repair and regeneration, but little is known about what determines their osteogenic capacity. Long non-coding RNAs (lncRNAs) are important regulatory molecules at both transcriptional and post-transcriptional levels. Ho...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1519-z
更新日期:2020-01-03 00:00:00
abstract:BACKGROUND:Treatment-induced cardiotoxicity is a leading noncancer-related cause of acute and late onset morbidity and mortality in cancer patients on antineoplastic drugs such as melphalan-increasing clinical case reports have documented that it could induce cardiotoxicity including severe arrhythmias and heart failur...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01984-1
更新日期:2020-11-05 00:00:00
abstract:BACKGROUND:Multiple sclerosis is a demyelinating disease mostly of autoimmune origin that affects and damages the central nervous system, leading to a disabling condition. The aim of the present study was to investigate whether administration of mesenchymal stem cells from human periodontal ligament (hPDLSCs) could ame...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0253-4
更新日期:2016-01-04 00:00:00
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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:BACKGROUND:Bone defects are a common clinical condition that has gained an increasing amount of attention in recent years. Causes of bone defect include tumors, inflammation, and fractures. Bone tissue engineering is a novel treatment of bone defect, and human mesenchymal stem cells (hMSCs) are the ideal seed cells for...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01631-9
更新日期:2020-03-25 00:00:00
abstract::Because of their multi/pluripotency and immunosuppressive properties, mesenchymal stem/stromal cells (MSCs) are important tools for treating immune disorders and for tissue repair. The increasing use of MSCs, their definition as advanced-therapy medicinal products in European regulations, and the US Food and Drug Admi...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/scrt217
更新日期:2013-06-07 00:00:00
abstract::The use of secretome may be a new strand of cell therapy, which is equal to or even superior to the injection of live cells, called cell-free therapy. In ovarian transplantation, this approach may be a therapeutic possibility for the ovarian graft in hypoxia. We designed the present study to evaluate whether the cell-...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-1054-3
更新日期:2018-11-21 00:00:00
abstract:INTRODUCTION:Short-term neural stem cell (NSC) transplantation improves cognition in Alzheimer's disease (AD) transgenic mice by enhancing endogenous synaptic connectivity. However, this approach has no effect on the underlying beta-amyloid (Aβ) and neurofibrillary tangle pathology. Long term efficacy of cell based app...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt440
更新日期:2014-04-16 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:Human adipose-derived stem cells (hASCs) are a subset of mesenchymal stem cells (MSCs); it has been regarded as one of the most promising stem cells. We previously found that fibroblast growth factor-2 (FGF-2) enhanced the proliferation and differentiation of hASC. However, the mechanisms involved in the gro...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1462-z
更新日期:2019-11-27 00:00:00
abstract:BACKGROUND:Efficient and sustained hematopoietic recovery after hematopoietic stem cell or bone marrow transplantation is supported by paracrine signaling from specific subpopulations of mesenchymal stromal cells (MSCs). Here, we considered whether in vitro mechanopriming of human MSCs could be administered to predicti...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-018-0982-2
更新日期:2018-10-24 00:00:00
abstract:BACKGROUND:Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) from the human umbilical cord have been studied extensively due to their immunomodulatory functions. Large-conductance Ca2+-activated K+ (BKCa channels) channels are involved in many inflammatory responses, but their involvement in the anti-inflammator...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01952-9
更新日期:2020-10-15 00:00:00