Abstract:
:Osteoarthritis (OA) remains an intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor α (TNFα) has been identified as a crucial effector modulating OA pathogenesis. This study aimed to investigate the therapeutic effects of Atsttrin, a novel TNFα blocker, on OA treatment. We developed genetically modified mesenchymal stem cells (MSCs) that expressed recombinant Atsttrin (named as MSC-Atsttrin). Expression levels of ADAMTS-5, MMP13, and iNOS of human chondrocytes were analyzed when cocultured with MSC-GFP/Atsttrin. OA animal models were induced by anterior cruciate ligament transection, and MSC-GFP/Atsttrin were injected into the articular cavity 1 week postsurgery. The results showed that MSC-Atsttrin significantly suppressed TNFα-driven up-regulation of matrix proteases and inflammatory factors. Intra-articular injection of MSC-Atsttrin prevented the progression of degenerative changes in the surgically induced OA mouse model. Additionally, levels of detrimental matrix hydrolases were significantly diminished. Compared with nontreated OA samples at 8 weeks postsurgery, the percentages of MMP13- and ADAMTS-5-positive cells were significantly reduced from 91.33% ± 9.87% to 24.33% ± 5.7% (p < .001) and from 91.33% ± 7.1% to 16.67% ± 3.1% (p < .001), respectively. Our results thus indicated that suppression of TNFα activity is an effective strategy for OA treatment and that intra-articular injection of MSCs-Atsttrin could be a promising therapeutic modality.
journal_name
Stem Cells Transl Medjournal_title
Stem cells translational medicineauthors
Xia Q,Zhu S,Wu Y,Wang J,Cai Y,Chen P,Li J,Heng BC,Ouyang HW,Lu Pdoi
10.5966/sctm.2014-0200subject
Has Abstractpub_date
2015-05-01 00:00:00pages
523-31issue
5eissn
2157-6564issn
2157-6580pii
sctm.2014-0200journal_volume
4pub_type
杂志文章abstract::Diabetes engenders the loss of pancreatic β-cell mass and/or function, resulting in insulin deficiency relative to the metabolic needs of the body. Diabetic care has traditionally relied on pharmacotherapy, exemplified by insulin replacement to target peripheral actions of the hormone. With growing understanding of th...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2013-0184
更新日期:2014-05-01 00:00:00
abstract::In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and va...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0101
更新日期:2014-11-01 00:00:00
abstract::Adipose-derived stem cell (ADSC)-based therapy is promising for critical limb ischemia (CLI) treatment, especially in patients with diabetes. However, the therapeutic effects of diabetic ADSCs (D-ADSCs) are impaired by the diabetes, possibly through intracellular reactive oxygen species (ROS) accumulation. The objecti...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2015-0380
更新日期:2017-01-01 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::Stem cell therapy is a promising strategy for tissue regeneration. The therapeutic benefits of cell therapy are mediated by both direct and indirect mechanisms. However, the application of stem cell therapy in the clinic is hampered by several limitations. This concise review provides a brief introduction into stem ce...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.17-0196
更新日期:2018-04-01 00:00:00
abstract::Tissue regeneration using progenitor cell-based therapy has the potential to aid in the healing of a diverse range of pathologies, ranging from short-gut syndrome to spinal cord lesions. However, there are numerous hurdles to be overcome prior to the widespread application of these cells in the clinical setting. One o...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2013-0035
更新日期:2013-09-01 00:00:00
abstract::Perivascular stem cells (PSCs) are the natural ancestors of mesenchymal stem cells (MSCs) and are the stem cells responsible for homeostasis and repair in vivo. Prospectively identified and isolated PSCs have demonstrated increased plasticity and osteogenic potential. Cells from the infrapatellar fat pad (IFP) have de...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0040
更新日期:2017-01-01 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::Functional hepatocytes, cardiomyocytes, neurons, and retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) or human induced pluripotent stem cells (hiPSCs) could provide a defined and renewable source of human cells relevant for cell replacement therapies, drug discovery, toxicology te...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0047
更新日期:2013-02-01 00:00:00
abstract::Mesenchymal stem cells (MSCs) are emerging as a promising therapeutic approach of cell-based therapy for a wide range of autoimmune disorders and degenerative diseases. In preclinical and clinical studies, MSCs have been shown to be highly efficient in treating graft-versus-host disease, systemic lupus erythematosus, ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.5966/sctm.2011-0019
更新日期:2012-01-01 00:00:00
abstract::Cancer stem cells play a critical role in disease initiation and insensitivity to chemotherapy in numerous hematologic malignancies and some solid tumors, and these stem cells need to be eradicated to achieve a cure. Key to successful targeting of cancer stem cells is to identify and functionally test critical target ...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.18-0247
更新日期:2019-08-01 00:00:00
abstract::Limbal stem cell (LSC) deficiency is a visually debilitating condition caused by abnormal maintenance of LSCs. It is treated by transplantation of donor-derived limbal epithelial cells (LECs), the success of which depends on the presence and quality of LSCs within the transplant. Understanding the immunobiological res...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2016-0175
更新日期:2017-03-01 00:00:00
abstract::Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persis...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0022
更新日期:2012-11-01 00:00:00
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...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.18-0045
更新日期:2018-10-01 00:00:00
abstract::Mesenchymal stem cells (multipotent stromal cells; MSCs) have been under investigation for the treatment of diverse diseases, with many promising outcomes achieved in animal models and clinical trials. The biological activity of MSC therapies has not been fully resolved which is critical to rationalizing their use and...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.19-0446
更新日期:2020-09-01 00:00:00
abstract::The method of isolation of bone marrow (BM) mesenchymal stem/stromal cells (MSCs) is a limiting factor in their study and therapeutic use. MSCs are typically expanded from BM cells selected on the basis of their adherence to plastic, which results in a heterogeneous population of cells. Prospective identification of t...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0155
更新日期:2013-08-01 00:00:00
abstract::Human induced pluripotent stem cells (hiPSCs) hold great potential for use in regenerative medicine, novel drug development, and disease progression/developmental studies. Here, we report highly efficient differentiation of hiPSCs toward a relatively homogeneous population of functional hepatocytes. hiPSC-derived hepa...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2012-0160
更新日期:2013-06-01 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::To optimize the regenerative proficiency of stem cells, a cardiopoietic protein-based cocktail consisting of multiple growth factors has been developed and advanced into clinical trials for treatment of ischemic heart failure. Streamlining the inductors of cardiopoiesis would address the resource intensive nature of t...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.20-0193
更新日期:2020-10-24 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::Cellular therapy is enabling new approaches to tackle significant unmet needs in areas such as regenerative medicine and immunotherapy. The pharmacology of cell therapeutics becomes of critical importance to assure that these new drugs work reproducibly and effectively. Cell pharmacology can benefit from adapting prin...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.19-0019
更新日期:2019-09-01 00:00:00
abstract::Diabetes is a major global health issue and the number of individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) increases annually across multiple populations. Research to develop a cure must overcome multiple immune dysfunctions and the shortage of pancreatic islet β cells, but these challenges have proven...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0078
更新日期:2017-08-01 00:00:00
abstract:UNLABELLED:Studies in hypertension (HTN) pharmacogenomics seek to identify genetic sources of variable antihypertensive drug response. Genetic association studies have detected single-nucleotide polymorphisms (SNPs) that link to drug responses; however, to understand mechanisms underlying how genetic traits alter drug ...
journal_title:Stem cells translational medicine
pub_type: 临床试验,杂志文章
doi:10.5966/sctm.2015-0126
更新日期:2015-12-01 00:00:00
abstract::Accumulating evidence indicates that stem cells (SCs) possess immunomodulatory, anti-inflammatory, and prohealing properties. The mechanisms underlying these functions are being investigated with the final goal to set a solid background for the clinical use of SCs and/or their derivatives. Specialized proresolving lip...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.19-0078
更新日期:2019-10-01 00:00:00
abstract::Induced pluripotent stem cells (iPSCs) offer an effective platform for studies of human physiology and have revealed new possibilities for disease modeling at the cellular level. These cells also have the potential to be leveraged in the practice of precision medicine, including personalized drug testing. Aortic disea...
journal_title:Stem cells translational medicine
pub_type: 杂志文章,评审
doi:10.1002/sctm.20-0322
更新日期:2021-02-01 00:00:00
abstract::Human pluripotent stem cells have the potential to promote biological studies and accelerate drug discovery efforts by making possible direct experimentation on a variety of human cell types of interest. However, stem cell cultures are generally heterogeneous and efficient differentiation and purification protocols ar...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0059
更新日期:2017-11-01 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:BACKGROUND:Tendon or ligament tears can decrease patients' quality of life. Many therapeutic interventions are available to treat such injuries. Mesenchymal stem cells (MSCs) have been shown to be effective in treating tendon or ligament tears; however, the use of stem cell-conditioned medium (CM) requires further inve...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.19-0388
更新日期:2020-08-01 00:00:00
abstract::Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide variety of cellular functions including the protective effects on damaged hearts. Here we investigated the antiaging properties of BMSCs and the underlying mechanism in a cellular model of cardiomyocyte senescence and a rat model of aging heart...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.5966/sctm.2014-0206
更新日期:2015-05-01 00:00:00
abstract::Repair of injured lungs represents a longstanding therapeutic challenge. We recently demonstrated that human and mouse embryonic lung tissue from the canalicular stage of development are enriched with lung progenitors, and that a single cell suspension of canalicular lungs can be used for transplantation, provided tha...
journal_title:Stem cells translational medicine
pub_type: 杂志文章
doi:10.1002/sctm.17-0149
更新日期:2018-01-01 00:00:00