Abstract:
INTRODUCTION:Mesenchymal stem cells (MSCs) are adult, multipotent, stem cells with immunomodulatory properties. The mechanisms involved in the capacity of MSCs to inhibit the proliferation of proinflammatory T lymphocytes, which appear responsible for causing autoimmune disease, have yet to be fully elucidated. One of the underlying mechanisms studied recently is the ability of MSCs to generate T regulatory (Treg) cells in vitro and in vivo from activated peripheral blood mononuclear cells (PBMC), T-CD4+ and also T-CD8(+) cells. In the present work we investigated the capacity of MSCs to generate Treg cells using T-CD4(+) cells induced to differentiate toward the proinflammatory Th1 and Th17 lineages. METHODS:MSCs were obtained from mouse bone marrow and characterized according to their surface antigen expression and their multilineage differentiation potential. CD4(+) T cells isolated from mouse spleens were induced to differentiate into Th1 or Th17 cells and co-cultured with MSCs added at day 0, 2 or 4 of the differentiation processes. After six days, CD25, Foxp3, IL-17 and IFN-γ expression was assessed by flow cytometry and helios and neuropilin 1 mRNA levels were assessed by RT-qPCR. For the functional assays, the 'conditioned' subpopulation generated in the presence of MSCs was cultured with concanavalin A-activated CD4(+) T cells labeled with carboxyfluorescein succinimidyl ester. Finally, we used the encephalomyelitis autoimmune diseases (EAE) mouse model, in which mice were injected with MSCs at day 18 and 30 after immunization. At day 50, the mice were euthanized and draining lymph nodes were extracted for Th1, Th17 and Treg detection by flow cytometry. RESULTS:MSCs were able to suppress the proliferation, activation and differentiation of CD4(+) T cells induced to differentiate into Th1 and Th17 cells. This substantial suppressive effect was associated with an increase of the percentage of functional induced CD4(+)CD25(+)Foxp3(+) regulatory T cells and IL-10 secretion. However, using mature Th1 or Th17 cells our results demonstrated that while MSCs suppress the proliferation and phenotype of mature Th1 and Th17 cells they did not generate Treg cells. Finally, we showed that the beneficial effect observed following MSC injection in an EAE mouse model was associated with the suppression of Th17 cells and an increase in the percentage of CD4(+)CD25(+)Foxp3(+) T lymphocytes when administrated at early stages of the disease. CONCLUSIONS:This study demonstrated that MSCs contribute to the generation of an immunosuppressive environment via the inhibition of proinflammatory T cells and the induction of T cells with a regulatory phenotype. Together, these results might have important clinical implications for inflammatory and autoimmune diseases.
journal_name
Stem Cell Res Therjournal_title
Stem cell research & therapyauthors
Luz-Crawford P,Kurte M,Bravo-Alegría J,Contreras R,Nova-Lamperti E,Tejedor G,Noël D,Jorgensen C,Figueroa F,Djouad F,Carrión Fdoi
10.1186/scrt216subject
Has Abstractpub_date
2013-06-04 00:00:00pages
65issue
3issn
1757-6512pii
scrt216journal_volume
4pub_type
杂志文章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: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: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:INTRODUCTION:Our previous works demonstrated that systemic orbital fat-derived stem cell (OFSC) transplantation was effective in ameliorating lipopolysaccharide (LPS)-induced extensive acute lung injury (ALI) in vivo mainly through paracrine regulation of macrophage-mediated cytokine-storm. In this study, we explore th...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt486
更新日期:2014-08-13 00:00:00
abstract:BACKGROUND:Autologous grafting, despite some disadvantages, is still considered the gold standard for reconstruction of maxillofacial bone defects. The aim of this study was to evaluate bone regeneration using bone marrow-derived mesenchymal stromal cells (MSCs) in a clinical trial, a less invasive approach than autolo...
journal_title:Stem cell research & therapy
pub_type: 临床试验,杂志文章
doi:10.1186/s13287-018-0951-9
更新日期:2018-08-09 00:00:00
abstract:INTRODUCTION:Advances in tendon engineering with mesenchymal stem cells (MSCs) are hindered by a need for cues to direct tenogenesis, and markers to assess tenogenic state. We examined the effects of factors involved in embryonic tendon development on adult MSCs, and compared MSC responses to that of embryonic tendon p...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0043-z
更新日期:2015-05-09 00:00:00
abstract:BACKGROUND:C-kit-positive cardiac stem cells (CSCs) have been shown to be a promising candidate treatment for myocardial infarction and heart failure. Insulin-like growth factor (IGF)-1 is an anabolic growth hormone that regulates cellular proliferation, differentiation, senescence, and death in various tissues. Althou...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0762-4
更新日期:2018-02-21 00:00:00
abstract:INTRODUCTION:Stem cell-based therapies are currently widely explored as a tool to treat neuroimmune diseases. Multipotent adult progenitor cells (MAPC) have been suggested to have strong immunomodulatory and neuroprotective properties in several experimental models. In this study, we investigate whether MAPC are of the...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0169-z
更新日期:2015-09-16 00:00:00
abstract:INTRODUCTION:Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy is a novel approach with great therapeutic potential for the treatment of lung diseases. Despite demonstration of MSC grafting, the populations of engrafted MSCs h...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-015-0081-6
更新日期:2015-05-20 00:00:00
abstract:BACKGROUND:miRNA expression profiles in ectopic endometrium (EC) serving as pathophysiologic genetic fingerprints contribute to determining endometriosis progression; however, the underlying molecular mechanisms remain unknown. METHODS:miRNA microarray analysis was used to determine the expression profiling of EC fres...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1388-5
更新日期:2019-09-23 00:00:00
abstract:BACKGROUND:Due to limitations of current angiogenesis assays, we aimed to develop a novel application of the rat aortic ring assay to assess the angiogenic potential of mesenchymal stromal cells (MSCs). First-trimester human umbilical cord-derived perivascular cells (FTM HUCPVCs) have multipotent characteristics and pr...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0631-1
更新日期:2017-08-14 00:00:00
abstract:BACKGROUND:Acute liver failure (ALF) is a complicated condition that is characterized by global hepatocyte death and often requires immediate liver transplantation. However, this therapy is limited by shortage of donor organs. Mesenchymal stem cells (MSCs) and hepatocytes are two attractive sources of cell-based therap...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01962-7
更新日期:2020-10-23 00:00:00
abstract:BACKGROUND:Chronic low back pain is a prevalent disability, often caused by intervertebral disc (IVD) degeneration. Mesenchymal stem cell (MSC) therapy could be a safe and feasible option for repairing the degenerated disc. However, for successful translation to the clinic, various challenges need to be overcome includ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01862-w
更新日期:2020-08-24 00:00:00
abstract:BACKGROUND:Using a toxin-induced nonhuman primate model of acute liver failure (ALF), we previously reported that peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) strongly suppresses the activation of circulating monocytes and interleukin-6 (IL-6) production, thereby disrupting the developm...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-1550-0
更新日期:2020-01-23 00:00:00
abstract:BACKGROUND:Islets of Langerhans transplantation is a promising therapy for type 1 diabetes mellitus, but this technique is compromised by transplantation stresses including inflammation. In other tissues, co-transplantation with mesenchymal stem cells has been shown to reduce damage by improving anti-inflammatory and a...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1190-4
更新日期:2019-03-12 00:00:00
abstract:INTRODUCTION:Administration of bone marrow-derived cells produces beneficial effects in experimental extrapulmonary acute respiratory distress syndrome (ARDS). However, there are controversies regarding the effects of timing of cell administration and initial insult severity on inflammatory response. We evaluated the e...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt334
更新日期:2013-10-13 00:00:00
abstract:BACKGROUND:The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0395-z
更新日期:2016-10-28 00:00:00
abstract:BACKGROUND:Bone reconstruction in congenital craniofacial differences, which affect about 2-3% of newborns, has long been the focus of intensive research in the field of bone tissue engineering. The possibility of using mesenchymal stromal cells in regenerative medicine protocols has opened a new field of investigation...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-02017-7
更新日期:2020-11-25 00:00:00
abstract:BACKGROUND:Optimal cell type as cell-based therapies for heart failure (HF) remains unclear. We sought to compare the safety and efficacy of direct intramyocardial transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CMs) and human induced pluripotent stem cell-derived mesenchymal stem cells (hiPSC...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1183-3
更新日期:2019-03-07 00:00:00
abstract:INTRODUCTION:Mesenchymal stem cells (MSCs) play a central role in mediating endogenous repair of cell and tissue damage. Biologic aging is a universal process that results in changes at the cellular and molecular levels. In the present study, the role of microRNA (miRNA) in age-induced molecular changes in MSCs derived...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/scrt90
更新日期:2011-11-14 00:00:00
abstract:BACKGROUND:Many studies have shown that long noncoding RNAs (lncRNAs) are closely related to the stimulation of osteogenic differentiation of adipose-derived stem cells (ADSCs) and the prevention of osteoporosis. Current research aimed to investigate the novel lncRNA and explored the function and molecular mechanism of...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01754-z
更新日期:2020-06-17 00:00:00
abstract:BACKGROUND:Cellular replacement strategies using human induced pluripotent stem cells (iPSCs) and their cardiac derivatives are emerging as novel treatments for post-myocardial infarction (MI) heart failure (HF); however, the mechanism of recovery of heart function is not very clear. The purpose of this study was to in...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01811-7
更新日期:2020-07-17 00:00:00
abstract::Stem cell behaviors are regulated by multiple microenvironmental cues. As an external signal, mechanical stiffness of the extracellular matrix is capable of governing stem cell fate determination, but how this biophysical cue is translated into intracellular signaling remains elusive. Here, we elucidate mechanisms by ...
journal_title:Stem cell research & therapy
pub_type: 杂志文章,评审
doi:10.1186/s13287-015-0083-4
更新日期:2015-05-27 00:00:00
abstract:BACKGROUND:Mesenchymal stem cells, including those derived from human adipose tissue (hASCs), are currently being widely investigated for cell therapy. However, when transplanted at the site of injury, the survival and engraftment rates of hASCs are low, mainly due to the harsh microenvironment they encounter, characte...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-020-01851-z
更新日期:2020-08-03 00:00:00
abstract:BACKGROUND:We aimed to determine and compare the in vitro effects of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) and mesenchymal stem cell supernatant (MSC-Sp) on the wound healing capacity of equine corneal fibroblasts using a scratch assay. METHODS:Bone marrow aspirates and eyes were collected fr...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-017-0577-3
更新日期:2017-05-25 00:00:00
abstract:BACKGROUND:Vascular injury is one of the most common detrimental effects of cancer radiotherapy on healthy tissues. Since the efficacy of current preventive and therapeutic strategies remains limited, the exploration of new approaches to treat radiation-induced vascular injury (RIV) is on high demands. The use of mesen...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-019-1197-x
更新日期:2019-03-13 00:00:00
abstract::The original article [1] contains an error in Fig. 5 whereby sub-Fig. 5c, d & 5e are mistakenly mixed-up. ...
journal_title:Stem cell research & therapy
pub_type: 已发布勘误
doi:10.1186/s13287-020-1553-x
更新日期:2020-01-23 00:00:00
abstract:BACKGROUND:Although the unconjugated secondary bile acids, specifically deoxycholic acid (DCA) and lithocholic acid (LCA), are considered to be risk factors for colorectal cancer, the precise mechanism(s) by which they regulate carcinogenesis is poorly understood. We hypothesize that the cytotoxic bile acids may promot...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0439-4
更新日期:2016-12-01 00:00:00
abstract:BACKGROUND:The transfection of human mesenchymal stem cells (hMSCs) with the hyperpolarization-activated cyclic nucleotide-gated ion channel 2 (HCN2) gene has been demonstrated to provide biological pacing in dogs with complete heart block. The mechanism appears to be the generation of the ion current (If) by the HCN2-...
journal_title:Stem cell research & therapy
pub_type: 杂志文章
doi:10.1186/s13287-016-0326-z
更新日期:2016-04-30 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