Abstract:
:We recently reported the isolation and characterization of a population of pancreatic progenitor cells (PPCs) from early trimester human fetal pancreata. The PPCs, being the forerunners of adult pancreatic cell lineages, were amenable to growth and differentiation into insulin-secreting islet-like cell clusters (ICCs) upon stimulation by adequate morphogens. Of note, a novel morphogenic factor, PDZ-domain containing-2 (PDZD2) and its secreted form (sPDZD2) were ubiquitously expressed in the PPCs. Our goals for this study were to evaluate the potential role of sPDZD2 in stimulating PPC differentiation and to establish the optimal concentration for such stimulation. We found that 10(-9)M sPDZD2 promoted PPC differentiation, as evidenced by the upregulation of the pancreatic endocrine markers (PDX-1, NGN3, NEURO-D, ISL-1, NKX 2.2, NKX 6.1) and INSULIN mRNA. Inhibited endogenous production of sPDZD2 suppressed expression of these factors. Secreted PDZD2 treatment significantly elevated the C-peptide content of the ICCs and increased the basal rate of insulin secretion. However, they remained unresponsive to glucose stimulation, reflected by a minimal increase in GLUT-2 and GLUCOKINASE mRNA expression. Interestingly, sPDZD2 treatment induced increased expression of the L-type voltage-gated calcium channel (Ca(v)1.2) in the ICCs, triggering calcium ion influx under KCl stimulation and conferring an ability to secrete insulin in response to KCl. Pancreatic progenitor cells from 10- and 13-week fetal pancreata showed peak expression of endogenous sPDZD2, implying that sPDZD2 has a specific role in islet development during the first trimester. In conclusion, our data suggest that sPDZD2 promotes functional maturation of human fetal PPC-derived ICCs, thus enhancing its transplanting potentials.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Leung KK,Suen PM,Lau TK,Ko WH,Yao KM,Leung PSdoi
10.1089/scd.2008.0325subject
Has Abstractpub_date
2009-09-01 00:00:00pages
979-90issue
7eissn
1547-3287issn
1557-8534journal_volume
18pub_type
杂志文章abstract::The difficulty in long-term expansion of mesenchymal stem cells (MSCs) using standard culture systems without the loss of their stem cell properties suggests that a critical feature of their microenvironment necessary for retention of stem cell properties is absent in these culture systems. We report here the reconsti...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0217
更新日期:2010-07-01 00:00:00
abstract::Amniotic fluid stem cells (AFSs) are interesting mesenchymal stem cells (MSCs) that are characterized by their great potential for cell proliferation and differentiation compared with other types of MSCs identified to date. However, MSCs in prolonged culture have been found to exhibit defects in genetic stability and ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0371
更新日期:2013-05-01 00:00:00
abstract::Body axes and germ layers evolve at gastrulation, and in mammals are driven by many genes; however, what orchestrates the genetic pathways during gastrulation remains elusive. Previously, we presented evidence that microRNA-17 (miRNA-17) family members, miR-17-5p, miR-20a, miR-93, and miR-106a were differentially expr...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0051
更新日期:2015-02-01 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::Gap junctions within extracellular matrix (ECM)-defined boundaries ensure synchronous activity between cells destined to become functional mediators that regulate cell behavior. However, the role of ECM in connexin (Cx) function in mouse embryonic stem cells (mESCs) has not been elucidated. Therefore, we examined the ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0505
更新日期:2012-07-20 00:00:00
abstract::The chemokine stromal cell-derived factor (SDF)-1α/CXCL12 and its receptor CXC chemokine receptor 4 (CXCR4) play a crucial role in the homing/engraftment and retention of hematopoietic stem/progenitor cells (HSPCs) in the bone marrow. It has been shown using the viral gene transfer technique that CXCR4 overexpression ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0297
更新日期:2012-07-01 00:00:00
abstract::Spinal cord injury (SCI) is a devastating medical condition with profound social and economic impacts. Although research is ongoing, current treatment options are limited and do little to restore functionality. However, recent studies suggest that mesenchymal stem cell-derived exosomes (MSC-exosomes) may hold the key ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2020.0133
更新日期:2020-12-01 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::Most disease-modifying therapeutic approaches in Alzheimer's disease (AD) aim to reduce the accumulation of neurotoxic amyloid-beta (Abeta) peptides as a hallmark of AD pathogenesis. Here we report the in vitro basis for a potential autologous stem cell-based strategy for widespread delivery of enzymatic activities ag...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0045
更新日期:2010-05-01 00:00:00
abstract::The capability to form all cell types of the body is a unique feature of stem cells. However, many questions remain concerning the mechanisms regulating differentiation potential. The derivation of spermatogonial cell lines (SGs) from mouse and human, which can differentiate across germ-layer borders, suggested male g...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0290
更新日期:2011-08-01 00:00:00
abstract::Umbilical cord blood (CB) CD34(+) cells, on the basis of flow cytometry analysis, are comprised of multiple populations. In in vitro assays, only CD34(regular) FSC(high) cells are functional and low percentages of nonfunctional CD34(regular) FSC(low) cells were determined to be present in liquid-stored CB. Liquid-stor...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.15.124
更新日期:2006-02-01 00:00:00
abstract::N-methyl-d-aspartate receptors (NMDARs) are expressed abundantly in the brain and play an important role in the regulation of neuronal development, learning, memory, neurodegenerative diseases, and neurogenesis, all of which are extensively discussed in reviews published elsewhere. While the number of research article...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2016.0325
更新日期:2017-06-01 00:00:00
abstract::The paired type homeobox 6 (Pax6) transcription factor (TF) regulates multiple aspects of neural stem cell (NSC) and neuron development in the embryonic central nervous system. However, less is known about the role of Pax6 in the maintenance and differentiation of adult NSCs and in adult neurogenesis. Using the +/Sey(...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0058
更新日期:2014-12-01 00:00:00
abstract::In the past few years research on stem cells has exploded as a tool to develop potential therapies to treat incurable neurodegenerative diseases. Stem cell transplantation has been effective in several animal models, but the underlying restorative mechanisms are still unknown. Several events such as cell fusion, neuro...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/154732804773099326
更新日期:2004-02-01 00:00:00
abstract::Traditionally, undifferentiated pluripotent human embryonic and induced pluripotent stem cells (hESCs and hiPSCs) have been expanded as monolayer colonies in adhesion culture, both in the presence or absence of feeder cells. However, the use of pluripotent stem cells poses the need to scale-up current culture methods....
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0517
更新日期:2011-11-01 00:00:00
abstract::Ex vivo cultures of human bone marrow-derived mesenchymal stem cells (MSCs) contain subsets of progenitors exhibiting dissimilar properties. One of these subsets comprises uncommitted progenitors displaying distinctive features, such as morphology, a quiescent condition, growth factor production, and restricted tissue...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2005.14.408
更新日期:2005-08-01 00:00:00
abstract::The projected annual demand for stem cell-based dental treatments in the United States can range from over 290 million tooth restorative treatments to 30,000 patients requiring tissue regeneration following craniofacial cancer surgery. Professional dental treatments cost Americans over $60 billion per year. Scientific...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2006.15.881
更新日期:2006-12-01 00:00:00
abstract::A long-term goal of mesenchymal progenitor cell (MPC) research is to identify cell-surface markers to facilitate MPC isolation. One reported MPC feature in humans and other species is lack of CD14 (lipopolysaccharide receptor) expression. The aim of this study was to evaluate CD14 as an MPC sorting marker. Our hypothe...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2010.0175
更新日期:2011-04-01 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::There are a limited number of therapies available to prevent heart failure following myocardial infarction. One novel therapy that is currently being pursued is the implantation of cardiac progenitor cells (CPCs); however, their responses to oxidative stress during differentiation have yet to be elucidated. The object...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0673
更新日期:2013-09-01 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::Central nervous system (CNS) inflammation is primarily driven by microglial cells which secrete proinflammatory cytokines and undergo proliferation upon activation, as it occurs in neurodegenerative diseases. Uncontrolled or prolonged CNS inflammation is potentially harmful and can result in cellular damage. Recently,...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0268
更新日期:2016-07-15 00:00:00
abstract::Mesenchymal stem cells (MSCs) have attracted much attention as potential platforms for transgene delivery and cell-based therapy for human disease. MSCs have the capability to self-renew and retain multipotency after extensive expansion in vitro, making them attractive targets for ex vivo modification and autologous t...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2007.0194
更新日期:2008-06-01 00:00:00
abstract::Neuroblastoma (NB) is the second most common solid cancer in childhood, accounting for 15% of cancer-related deaths in children. In high-risk NB patients, the majority suffers from metastasis. Despite intensive multimodal treatment, long-term survival remains <40%. The bone marrow (BM) is among the most common sites o...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2020.0142
更新日期:2021-01-15 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::Although amniotic fluid cells can differentiate into several mesenchymal lineages and have been proposed as a valuable therapeutic cell source, their ability to undergo terminal neuronal differentiation remains a cause of controversy. The aim of this study was to investigate the neuronal differentiation ability of the...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0281
更新日期:2012-03-20 00:00:00
abstract::We describe a method of generating an enriched population of NCAM-positive cells from a human teratocarcinoma cell line (NTera2/D1) and their differentiation into midbrain dopaminergic neurons in the absence of the caudalizing factor retinoic acid (RA). NTera2 cells were induced to form embryoid bodies and then to gen...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2006.15.575
更新日期:2006-08-01 00:00:00
abstract::One of the challenges in stem cell research is to avoid transformation during cultivation. We studied high passage subventricular zone derived neural stem cells (NSCs) cultures of adult rats in the absence of growth factors epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF). We termed this culture...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0416
更新日期:2010-07-01 00:00:00
abstract::Bone marrow mesenchymal stem cells (BMMSCs) have been used to treat a variety of autoimmune diseases in clinics. However, the therapeutic effects are largely dependent on the immunomodulatory capacity of culture-expanded BMMSCs. In the present study, we show that aspirin (acetylsalicylic acid, ASA)-treated BMMSCs have...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2014.0081
更新日期:2014-09-01 00:00:00
abstract::Mesenchymal stem cells (MSC) possess a range of immunomodulatory properties which they exert through soluble mediators and through direct cell-cell contact. Due to these immune regulatory properties, the safety and clinical efficacy of MSC treatment has been tested in a number of autoimmune disorders. In this review w...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2015.0008
更新日期:2015-09-15 00:00:00