Abstract:
:The potential of autologous cell-based therapies including those using multipotent mesenchymal stromal cells (MSCs) is being investigated for multiple sclerosis (MS) and other neurological conditions. However, the phenotype of MSC in neurological diseases has not been fully characterized. We have previously shown that MSC isolated from patients with progressive MS (MS-MSC) have reduced expansion potential, premature senescence, and reduced neuroprotective potential in vitro. In view of the role of antioxidants in ageing and neuroprotection, we examined the antioxidant capacity of MS-MSC demonstrating that MS-MSC secretion of antioxidants superoxide dismutase 1 (SOD1) and glutathione S-transferase P (GSTP) is reduced and correlates negatively with the duration of progressive phase of MS. We confirmed reduced expression of SOD1 and GSTP by MS-MSC along with reduced activity of SOD and GST and, to examine the antioxidant capacity of MS-MSC under conditions of nitrosative stress, we established an in vitro cell survival assay using nitric oxide-induced cell death. MS-MSC displayed differential susceptibility to nitrosative stress with accelerated senescence and greater decline in expression of SOD1 and GSTP in keeping with reduced expression of master regulators of antioxidant responses nuclear factor erythroid 2-related factor 2 and peroxisome proliferator-activated receptor gamma coactivator 1-α. Our results are compatible with dysregulation of antioxidant responses in MS-MSC and have significant implications for development of autologous MSC-based therapies for MS, optimization of which may require that these functional deficits are reversed. Furthermore, improved understanding of the underlying mechanisms may yield novel insights into MS pathophysiology and biomarker identification. Stem Cells Translational Medicine 2018;7:748-758.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Redondo J,Sarkar P,Kemp K,Heesom KJ,Wilkins A,Scolding NJ,Rice CMdoi
10.1002/sctm.18-0045subject
Has Abstractpub_date
2018-10-01 00:00:00pages
748-758issue
10eissn
2157-6564issn
2157-6580journal_volume
7pub_type
杂志文章abstract:UNLABELLED:Histone deacetylase (HDAC) inhibitors possess therapeutic potential to reverse aberrant epigenetic changes associated with cancers, neurological diseases, and immune disorders. Unfortunately, clinical studies with some HDAC inhibitors displayed delayed cardiac adverse effects, such as atrial fibrillation and...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0279
更新日期:2016-05-01 00:00:00
abstract:UNLABELLED:We evaluated the association of diabetes and insulin resistance with the response to cell therapy in patients with nonischemic dilated cardiomyopathy (DCM). A total of 45 outpatients with DCM received granulocyte colony-stimulating factor for 5 days. CD34(+) cells were then collected by apheresis and injecte...
journal_title:Stem cells translational medicine
pub_type: 临床试验,杂志文章
doi:10.5966/sctm.2015-0172
更新日期:2016-05-01 00:00:00
abstract::The specific cell surface markers on mesenchymal stem/progenitor cells (MSCs) have been poorly defined in vivo, but in one recent study, an MSC subpopulation was directly isolated from a CD271-positive fraction of human bone marrow cells. The aim of this study was to identify circulating CD271(+) MSCs in human periphe...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2011-0051
更新日期:2012-06-01 00:00:00
abstract::Adipose-derived stem cells (ASCs) are being tested in clinical trials related to cell-based regenerative therapies. Although most of the current expansion protocols for ASCs use fetal calf serum (FCS), xenogeneic-free medium supplements are greatly desired. This study aims to compare the effect of FCS, human platelet ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0148
更新日期:2016-03-01 00:00:00
abstract::Organoids are three-dimensional culture systems in which adult stem cells and their progeny grow and represent the native physiology of the cells in vivo. Organoids have been successfully derived from several organ systems in both animal models and human patients. Organoids have been used for fundamental research, dis...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2015-0152
更新日期:2016-03-01 00:00:00
abstract:UNLABELLED:Cell secretion is an important mechanism for stem cell-based therapeutic angiogenesis, along with cell differentiation to vascular endothelial cells or smooth muscle cells. Cell-released microvesicles (MVs) have been recently implicated to play an essential role in intercellular communication. The purpose of...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0177
更新日期:2016-04-01 00:00:00
abstract:UNLABELLED:: Induced pluripotent stem cells (iPSCs) are new diagnostic and potentially therapeutic tools to model disease and assess the toxicity of pharmaceutical medications. A common limitation of cell lineages derived from iPSCs is a blunted phenotype compared with fully developed, endogenous cells. We examined the...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0235
更新日期:2016-09-01 00:00:00
abstract::There is a need among patients suffering from drug-resistant epilepsy (DRE) for more efficient and less toxic treatments. The objective of the present study was to assess the safety, feasibility, and potential efficacy of autologous bone marrow cell transplantation in pediatric patients with DRE. Two females and two m...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0041
更新日期:2018-01-01 00:00:00
abstract::An important stage in the development of any new therapeutic agent is establishment of the optimal dosage and route of administration. This can be particularly challenging when the treatment is a biologic agent that might exert its therapeutic effects via complex or poorly understood mechanisms. Multiple preclinical a...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2015-0101
更新日期:2016-02-01 00:00:00
abstract:UNLABELLED:Rotator cuff tendon tear is one of the most common causes of chronic shoulder pain and disability. In this study, we investigated the therapeutic effects of ultrasound-guided human umbilical cord blood (UCB)-derived mesenchymal stem cell (MSC) injection to regenerate a full-thickness subscapularis tendon tea...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0040
更新日期:2015-11-01 00:00:00
abstract::Human-induced pluripotent stem cells (hiPSCs)-based cell therapy holds promise for treating stress urinary incontinence (SUI). However, safety concerns, especially tumorgenic potential of residual undifferentiated cells in hiPSC derivatives, are major barriers for its clinical translation. An efficient, fast and clini...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.16-0160
更新日期:2017-04-01 00:00:00
abstract::Diabetes is a risk factor for worse outcomes following acute myocardial infarction (AMI). In this study, we tested the hypothesis that SDF-1:CXCR4 expression is compromised in post-AMI in diabetes, and that reversal of this defect can reverse the adverse effects of diabetes. Mesenchymal stem cells (MSC) isolated from ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0172
更新日期:2018-01-01 00:00:00
abstract::Cancer stem cells (CSCs) are a subpopulation of tumor cells that have strong self-renewal capabilities and may contribute to the failure of conventional cancer therapies. Hence, therapeutics homing in on CSCs represent a novel and promising approach that may eradicate malignant tumors. However, the lack of information...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0289
更新日期:2017-02-01 00:00:00
abstract::Niemann-Pick disease, type C1 (NPC1) is a familial disorder that has devastating consequences on postnatal development with multisystem effects, including neurodegeneration. There is no Food and Drug Administration-approved treatment option for NPC1; however, several potentially therapeutic compounds have been identif...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0127
更新日期:2015-03-01 00:00:00
abstract::Adult hemoglobin composed of α- and β-globin reflects a change from expression of embryonic ε- and fetal γ-globin to adult β-globin in human erythroid cells, so-called globin switching. Human pluripotent stem cells (hPSCs) are a potential source for in vitro erythrocyte production, but they show prominent expression o...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0216
更新日期:2014-07-01 00:00:00
abstract::Basic and translational research on lung biology has discovered multiple progenitor cell types, specialized or facultative, responsible for turnover, renewal, and repair. Isolation of populations of resident lung progenitor cells (LPCs) has been described by multiple protocols, and some have been successfully applied ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0374
更新日期:2017-03-01 00:00:00
abstract::Stem cells are promising candidate cells for regenerative applications because they possess high proliferative capacity and the potential to differentiate into other cell types. Mesenchymal stem cells (MSCs) are easily sourced but do not retain their proliferative and multilineage differentiative capabilities after pr...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0079
更新日期:2014-02-01 00:00:00
abstract::Lamin A (LMNA)-linked lipodystrophies may be either genetic (associated with LMNA mutations) or acquired (associated with the use of human immunodeficiency virus protease inhibitors [PIs]), and in both cases they share clinical features such as anomalous distribution of body fat or generalized loss of adipose tissue, ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2011-0010
更新日期:2012-04-01 00:00:00
abstract::Strategies for musculoskeletal tissue regeneration apply adult mesenchymal stem/stromal cells (MSCs) that can be sourced from bone marrow- and lipo-aspirates. Adipose tissue-derived MSCs are more easily harvested in the large quantities required for skeletal tissue-engineering approaches, but are generally considered ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0086
更新日期:2018-02-01 00:00:00
abstract::Infection with the SARS-CoV-2 virus has rapidly become a global pandemic for which we were not prepared. Several clinical trials using previously approved drugs and drug combinations are urgently under way to improve the current situation. A vaccine option has only recently become available, but worldwide distribution...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.20-0181
更新日期:2021-02-01 00:00:00
abstract::Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically complian...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0015
更新日期:2014-10-01 00:00:00
abstract:UNLABELLED:Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is the most common muscular dystrophy. Characterized by rounds of muscle degeneration and regeneration, DMD features progressive muscle wasting and is fatal. One approach for treatment is transplantation of muscle progenitor cells...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0169
更新日期:2016-04-01 00:00:00
abstract::There has been considerable progress in obtaining engraftable embryonic stem (ES) cell-derived midbrain dopamine neurons for cell replacement therapy in models of Parkinson's disease; however, limited integration and striatal reinnervation of ES-derived grafts remain a major challenge for future clinical translation. ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0084
更新日期:2014-01-01 00:00:00
abstract::Patients with laryngeal disorders may have severe morbidity relating to swallowing, vocalization, and respiratory function, for which conventional therapies are suboptimal. A tissue-engineered approach would aim to restore the vocal folds and maintain respiratory function while limiting the extent of scarring in the r...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0130
更新日期:2017-02-01 00:00:00
abstract::Patient-specific induced pluripotent stem cells (iPSCs) hold great promise for studies on disease-related developmental processes and may serve as an autologous cell source for future treatment of many hereditary diseases. New genetic engineering tools such as zinc finger nucleases and transcription activator-like eff...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0017
更新日期:2013-09-01 00:00:00
abstract::Esophageal anastomotic leakage (EAL) is a devastating complication for esophagectomy but the available therapies are unsatisfactory. Due to the healing effects of mesenchymal stromal cells (MSCs) and supporting capability of fibrin scaffold (FS), we evaluated the efficacy of a stem-cell therapy for EAL by engrafting a...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.18-0137
更新日期:2019-06-01 00:00:00
abstract::Heart diseases (HDs) are the leading cause of morbidity and mortality worldwide. Despite remarkable clinical progress made, current therapies cannot restore the lost myocardium, and the correlation of genotype to phenotype of many HDs is poorly modeled. In the past two decades, with the rapid developments of human plu...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.19-0340
更新日期:2020-10-01 00:00:00
abstract::Recent reports have indicated human embryonic stem cells-derived midbrain dopamine (mDA) neurons as proper cell resources for use in Parkinson's disease (PD) therapy. Nevertheless, no detailed and systematic study has been conducted to identify which differentiation stages of mDA cells are most suitable for transplant...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.16-0470
更新日期:2017-09-01 00:00:00
abstract::Gaucher disease, the most prevalent metabolic storage disorder, is caused by mutations in the glucocerebrosidase gene GBA1, which lead to the accumulation of glucosylceramide (GlcCer) in affected cells. Gaucher disease type 1 (GD1), although defined as nonneuronopathic subtype, is accompanied by an increased risk of P...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.20-0302
更新日期:2020-12-20 00:00:00
abstract:UNLABELLED:: Present therapies for stroke rest with tissue plasminogen activator (tPA), the sole licensed antithrombotic on the market; however, tPA's effectiveness is limited in that the drug not only must be administered less than 3-5 hours after stroke but often exacerbates blood-brain barrier (BBB) leakage and incr...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0184
更新日期:2015-07-01 00:00:00