Abstract:
:Small-molecule inhibitors of glycogen synthase kinase 3β (GSK3β) have demonstrated strong anti-leukemia effects in preclinical studies. Here, we investigated the effect of GSK3β inhibitor 6-Bromoindirubin-3-oxime (BIO) previously shown to inhibit leukemia cell growth in vitro and of animal models on hematopoietic regeneration in recipients of stem cell transplant. BIO administered to immunocompromised mice transplanted with human hematopoietic stem cells inhibited human stem cell engraftment in the bone marrow (BM) and peripheral blood. BIO reduced CD34(+) progenitor cells in the BM, and primitive lymphoid progenitors re-populated host thymus at later stages post-transplant. The development of all T-cell subsets in the thymus was suppressed in BIO-treated mice. Human cell engraftment was gradually restored after discontinuation of BIO treatment; however, T-cell depletion remained until the end of experiment, which correlated with the attenuated thymic function in the host. BIO delayed CD34(+) cell expansion in stroma-supported or cytokine-only cultures. BIO treatment delayed progenitor cell divisions and induced apoptosis in cultures with sub-optimal cytokine support. In addition, BIO inhibited B- and T-cell development in co-cultures with MS5 and OP9-DL1 BM stroma cells, respectively. These data suggest that administration of GKS3β inhibitors may act to delay hematopoietic regeneration in patients who received stem cell transplant.
journal_name
Stem Cells Devjournal_title
Stem cells and developmentauthors
Shen S,Xu N,Klamer G,Ko KH,Khoo M,Ma D,Moore J,O'Brien TA,Dolnikov Adoi
10.1089/scd.2014.0230subject
Has Abstractpub_date
2015-03-15 00:00:00pages
724-36issue
6eissn
1547-3287issn
1557-8534journal_volume
24pub_type
杂志文章abstract::Bone marrow mesenchymal stem cells (MSCs) have shown potential to improve treatment of renal failure. The prohealing functions of MSCs have been found to be enhanced by treatment with the lipid mediator, 14S,21R-dihydroxy-docosa4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid (14S,21R-diHDHA). In this article, using a murine mode...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0220
更新日期:2012-05-01 00:00:00
abstract::Bone marrow-derived mesenchymal stem cells (MSCs) possess multilineage differentiation potential and can be used for the treatment of diabetic heart failure. However, hyperglycemia can affect the function of MSCs adversely and merits the requirement for a strategy to correct this anomaly. MSCs were isolated from the t...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0397
更新日期:2011-01-01 00:00:00
abstract::Human embryonic stem cells (hESCs) self-renew indefinitely as highly organized pluripotent colonies. Unlike mouse pluripotent stem cell colonies, human colonies form a uniform, flat, epithelium-like monolayer. Interestingly, it has been reported that colony morphology is closely correlated with the maintenance of plur...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0288
更新日期:2013-01-15 00:00:00
abstract::In this retrospective study, 209 patients with malignant disease were analyzed for levels of T-cell receptor excision circles (TRECs) for the first 24 months after allogeneic stem cell transplantation. CD3(+) cells were separated by direct antibody-coupled magnetic beads, followed by DNA extraction according to a stan...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0588
更新日期:2014-07-15 00:00:00
abstract::Since human mesenchymal stem cells (MSCs) are therapeutically attractive for tissue regeneration and repair, we examined the physiological responses of human umbilical cord blood-derived MSCs (hUCB-MSCs) to genotoxic stress. We found that that sublethal doses of reactive oxygen species (ROS) and ionizing radiation cau...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0284
更新日期:2012-07-20 00:00:00
abstract::Spiral ganglion neurons (SGNs) are usually damaged in sensorineural hearing loss. SGN-derived neural stem cells (NSCs) have been identified and proposed to differentiate into neurons to replace damaged SGNs. However, it remains obscure whether SGN-NSC-derived neurons (ScNs) are electrophysiologically functional and po...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0345
更新日期:2016-05-15 00:00:00
abstract::Hematopoietic stem cells (HSCs) possess a distinct ability to perpetuate through self-renewal and to generate progeny that differentiate into mature cells of myeloid and lymphoid lineages. A better understanding of the molecular mechanisms by which HSCs replicate and differentiate from the perspective of developing ne...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2006.15.755
更新日期:2006-12-01 00:00:00
abstract::Non-tumorous liver tissue removed during surgery to resect hepatocellular carcinoma (HCC) is potentially a useful source of material from which cells, particularly liver progenitor/stem cells (LPCs), can be isolated to establish cell lines. The purpose of this study was to evaluate the applicability of the "plate-and-...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0304
更新日期:2010-08-01 00:00:00
abstract::Myocardial infarction is a major public health problem that causes significant mortality despite recent advances in its prevention and treatment. Therefore, approaches based on adult stem cells represent a promising alternative to conventional therapies for this life-threatening condition. Mesenchymal stem cells (MSCs...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0292
更新日期:2009-07-01 00:00:00
abstract::The mechanisms responsible for the inhibitory effects of mesenchymal stem cells (MSCs) on dendritic cells (DCs) are still poorly understood. Our investigation of the potential signaling pathways revealed for the first time that human umbilical-cord-derived MSCs (UC-MSCs) instruct DCs to acquire tolerogenic phenotypes ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0559
更新日期:2014-09-01 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::Transplantation of neural stem/progenitor cells (NSPCs) is a promising strategy for repair of the diseased/injured central nervous system (CNS); however, controlling their differentiation remains a significant hurdle. This study is aimed at controlling differentiation and specifically at screening exogenous factors to...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0412
更新日期:2009-12-01 00:00:00
abstract::Although the pluripotent and proliferative capacity of embryonic germ (EG) cells is thought to be equivalent to that of embryonic stem (ES) cells, there has been far less attention focused on the potential use of EG cells for applications in developing novel strategies of tissue transplantation in the treatment of deg...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0383
更新日期:2010-02-01 00:00:00
abstract::The AMP-activated protein kinase (AMPK) mediates rapid, stress-induced loss of the inhibitor of differentiation (Id)2 in blastocysts and trophoblast stem cells (TSC), and a lasting differentiation in TSC. However, it is not known if AMPK regulates other potency factors or regulates them before the blastocyst stage. Th...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0352
更新日期:2013-05-15 00:00:00
abstract::Immune suppression is a very stable property of multipotent stromal cells also known as mesenchymal stem cells (MSCs). All cell lines tested showed robust immune suppression not affected by a long culture history. Several mechanisms were described to account for this capability. Since several of the described mechanis...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0433
更新日期:2014-07-15 00:00:00
abstract::Human embryonic stem cells (hESCs) are derived from the inner cell mass (ICM) of the blastocyst and can differentiate into any cell type in the human body. These cells hold a great potential for regenerative medicine, but to obtain enough cells needed for medical treatment, culture is required on a large scale. In the...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0239
更新日期:2013-04-01 00:00:00
abstract::The optimization of defined growth conditions is necessary for the development of clinical application of human embryonic stem cells (hESCs). Current research has focused on developing defined media formulations for long-term culture of hESCs with little attention on the establishment of defined substrates for hESC pr...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0410
更新日期:2009-10-01 00:00:00
abstract::The reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) is a complex process that involves significant epigenetic alterations in the reprogrammed cells. Epigenetic modifiers such as histone deacetylase (HDAC) inhibitors have been shown to increase the efficiency of derivation of iPSCs in humans an...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2015.0317
更新日期:2016-03-01 00:00:00
abstract::Transplantation of retinal cells has recently provided a promising therapeutic approach for retinal degeneration. Here, we differentiated initially retinal progenitors (RPs) from adherent feeder-free human embryonic stem cells (hESCs) with the use of defined media supplemented with a specific combination of growth fac...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0073
更新日期:2012-01-01 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::Regenerative medicine, a paragon of future healthcare, holds unprecedented potential in extending the reach of treatment modalities for individuals across diseases and lifespan. Emerging regenerative technologies, focused on structural repair and functional restoration, signal a radical transformation in medical and s...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0448
更新日期:2013-12-01 00:00:00
abstract::Stem cell therapy is a promising therapeutic strategy for treating myocardial infarction (MI). However, it is necessary to identify ideal adult stem cells for transplantation and explore mechanisms of the transplanted cells in improving cardiac functions after MI. In this study, a population of embryonic-like stem cel...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0280
更新日期:2012-05-20 00:00:00
abstract::Geminin is a multifunctional protein previously suggested to both maintain the bone morphogenetic protein inhibition required for neural induction and to control cell-cycle progression and cell fate in the early embryo. Since Geminin is required in the blastocyst on E3.5, we employed shRNA to examine its role during p...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2011.0483
更新日期:2012-09-01 00:00:00
abstract::The success rate of human embryonic stem cell (hESC) derivation depends on both culture conditions and embryo quality and is routinely determined by morphological criteria. However, high incidence of chromosomal abnormality even in high-grade cleavage embryos from in vitro fertilization (IVF) patients suggests that th...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2009.0136
更新日期:2010-01-01 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
更新日期:2016-06-01 00:00:00
abstract::Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming ne...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0451
更新日期:2013-05-15 00:00:00
abstract::We have isolated a novel progenitor cell population from adult rat pancreatic ducts, termed pancreatic-derived progenitor cells (PDPCs). Here, we report the in vitro culture, selection, and characterization of Thy1.1-positive and Thy1.1-negative PDPC subpopulations. These cells exhibit bipotentiality for differentiati...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2008.0301
更新日期:2009-12-01 00:00:00
abstract::This study was undertaken to establish rat embryonic stem (ES) cells from parthenogenetically developing blastocysts. Ten blastocysts were prepared by treatment of ovulated rat oocytes with ionomycin and cycloheximide, and three alkaline phosphatase-positive ES cell lines were established using the N2B27 medium supple...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2013.0200
更新日期:2014-01-15 00:00:00
abstract::Adipose tissue (AT) is composed of mature adipocytes and stromal vascular fraction (SVF) cells, including adipose stem/stromal cells (ASCs). We characterized hematopoietic cells residing in human nonobese AT by analyzing the SVF isolated from human lipoaspirates and peripheral blood (PB). Flow cytometry revealed that ...
journal_title:Stem cells and development
pub_type: 杂志文章
doi:10.1089/scd.2012.0442
更新日期:2013-03-15 00:00:00
abstract::Diseases of the digestive tract are complex and encompass a broad spectrum of different pathogeneses (inflammatory, ischemic, neoplastic, and functional deficit). The digestive tract is not a sterile environment, and its organs are composed of tissues with different embryologic origin and different morphologic and fun...
journal_title:Stem cells and development
pub_type: 杂志文章,评审
doi:10.1089/scd.2010.0277
更新日期:2011-07-01 00:00:00