Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine‐induced killer/natural killer cells either by direct or indirect interaction

Yang, Li; Qu, Yu; Wu, Yan; Liu, Ling; Lin, Xiang; Huang, Ke; Wei, Jing

doi:10.1002/cbin.10404

Cited by 23 publications

(14 citation statements)

References 34 publications

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“…shown to inhibit the proliferation of activated T cells in vitro and in vivo. Besides, compared with NK cells cultured alone, MSCs highly elevated NK cells' apoptosis rate in co-cultures, this finding was different from another scholar,31 and this might be due to the different cytokines and their concentration. In the present study, BMMSCs and DPSCs were observed to inhibit the proliferation of NK cells; this was similar to the most studies.…”

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confidence: 84%

Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti‐inflammatory purinergic signalling in activated NK cells

et al. 2019

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Objectives: Mesenchymal stem cells (MSCs) could regulate the function of various immune cells. It remains unclear whether MSCs additionally possess immunostimulatory properties. We investigated the impact of human MSCs on the responsiveness of primary natural killer (NK) cells in terms of induction of anti-inflammatory purinergic signalling. Material and Methods:We obtained human bone marrow mesenchymal stem cells (BMMSCs) and dental pulp stem cells (DPSCs). NK cells were isolated from peripheral blood of healthy volunteers. Activated NK cells were cultured with MSCs. Proliferation assay, apoptosis analysis, activating or inhibitory receptor expression and degranulation assay were used to explore NK cells' function. High-performance liquid chromatography was used to investigate the purinergic signalling in activated NK cells.Results: Both DPSCs and BMMSCs could impair proliferation and promote apoptosis of activated NK cells. Also, activated NK cells could cause DPSCs to lyse. Furthermore, the expression of activating NK cells' receptors was decreased, but inhibitory receptors of NK cells were elevated following co-cultivation. NK cells acquired CD73 expression, while MSCs could release ATP into the extracellular space where nucleotides were converted into adenosine (ADO) following co-culture system. Under the existence of exogenous 2-chloroadenosine (CADO), the cytotoxic capacity of NK cells was remarkably depressed in a concentration-dependent manner. Conclusions: DPSCs and BMMSCs could depress NK cells' function by hydrolysingATP to ADO using CD39 and CD73 enzymatic activity. Our data suggested that DPSCs might represent a new strategy for treating immune-related diseases by regulating previously unrecognized functions in innate immune responses.

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confidence: 84%

Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti‐inflammatory purinergic signalling in activated NK cells

et al. 2019

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“…MSCs are frequently used, either as cellular therapy or within implanted material, in the clinical setting for orthopedic injuries, cardiovascular diseases and other pathological conditions, such as cardiac tissue repair following myocardial infarction . MSCs are present in most tissues and contribute to tissue regeneration, thanks to their ability to differentiate toward mesodermal lineages and to modulate the tissue immune microenvironment . hMSCs have been shown to mediate immune‐modulation, not only by increasing the proportion of CD8 + CD28 − T reg ‐cells, but also enhancing their ability to hamper naïve CD4 + T‐cell proliferation and activation, as shown by in vitro coculture of hMSCs with T cells .…”

Section: Interaction Between Immune Cells and Other Cell Populations mentioning

confidence: 99%

Inflammation in tissue engineering: The Janus between engraftment and rejection

et al. 2015

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Tissue engineering (TE) for tissue and organ regeneration or replacement is generally performed with scaffold implants, which provide structural and molecular support to in vitro seeded or in vivo recruited cells. TE implants elicit the host immune response, often resulting in engraftment impediment or rejection. Besides this negative effect, however, the immune system components also yield a positive influence on stem cell recruitment and differentiation, allowing tissue regeneration and healing. Thus, a balanced cooperation between proinflammatory and proresolution players of the immune response is an essential element of implant success. In this context, macrophage plasticity plays a fundamental role. Therefore modulating the immune response, instead of immune suppressing the host, might be the best way to successfully implant TE tissues or organs. In particular, it is becoming evident that the scaffold, immune, and stem cells are linked by a three-way interaction, and many efforts are being made for scaffold-appropriate design and functionalization in order to drive the inflammation process toward regeneration, vascularization, and implant success. This review discusses current and potential strategies for inflammation modulation to aid engraftment and regeneration, supporting the concept that quality, and not quantity, of inflammation might influence implant success.Keywords: Implant r Macrophage r Scaffold r Stem cell r Tissue engineering IntroductionTissue engineering and regenerative medicine (TERM) applications intend to improve or replace compromised biological functions by stimulating the intrinsic regenerative capacity of the body or even by replacing damaged tissues and organs. To provide the structure and attachment surface to drive tissue regeneration, Correspondence: Prof. Laura Teodori e-mail: laura.teodori@enea.it scaffolds of synthetic, or natural origin, which may or may not be seeded with stem cells, are constructed and implanted into the human body to foster regeneration. Scaffolds are particularly important for the replacement of a variety of tissues such as skin, bone, and muscle tissue (e.g. maxillofacial reconstructions, heart valves, and vessels) [1]. Depending on the type of tissue to be * These authors contributed equally to this work.C 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2015. 45: 3222-3236 HIGHLIGHTS 3223replaced, different types of scaffolds are suitable to support regeneration and engraftment. This review provides a general view on the different biomaterials/scaffold types and properties; however the available literature on the matter extensively reports the most frequently used types of scaffolds and their application [2,3]. Although TERM research greatly advanced in recent years, one major challenge is the immune response elicited by the implant, which often leads to a precocious reabsorption, to fibrosis of the implant, and/or to implant rejection, leading to eventual failure of the intervention [4]. To ensure the success of t...

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“…It should be noted that transplantation of MSCs from other sources have been shown to escalate Treg population as a mechanism of exerting immunosuppression [53,54]. For example, in a 25-yearold severe SLE patient with multiple life-threatening complications and refractory to conventional cyclophosphamide (CYC) therapy, Wang et al [55], reported that transplantation of autologous hematopoietic stem cell and MSCs re-established self-tolerance in SLE by increasing CD4+CD25+FoxP3+Treg cells in PBMCs.…”

Section: Discussionmentioning

confidence: 99%

Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

Li¹,

Ju²,

Zhou³

et al. 2015

Stud Stem Cells Res Ther

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Despite considerable advances in the treatment for systemic lupus erythematosus (SLE), there is still an unmet need to develop novel therapeutic approaches with improved efficacy and lower side effects. Here we explore human umbilical cord-derived mesenchymal stem cells (hUCMSCs) as a promising treatment for SLE induced by concanavalin A-activated spleno-lymphocyte in BALB/c mice. The isolated hUCMSCs, carrying specific MSC cell surface markers (CD105, CD73 and CD90), exhibited the potential to differentiate into osteogenic and adipogenic lineages. In mice with SLE, transplantation of hUCMSCs improved disease symptoms by decreasing the levels of serum autoantibody (antidsDNA and anti-nuclear) and cytokines (TNF-α and IFN-γ). The cell therapy significantly alleviated renal lesions by lowering serum urea nitrogen, creatine and uric acid, and increasing albumin. Using immunohistochemical staining, we found that that hUCMSCs decreased endocapillary hypercellularity, glomerular degeneration, and complement C3 immune complex deposition in the kidney. Mechanically, the therapy with hUCMSCs decreased CD4+/CD8+ cell ratio in animals. These data suggest that hUCMSCs may modulate autoimmunity in SLE mice by rebalancing CD4+/CD8+ cell population. Transplantation of hUCMSCs may be explored as a promising alternative approach in the treatment of human lupus.

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Bone marrow mesenchymal stem cells suppressing activation of allogeneic cytokine‐induced killer/natural killer cells either by direct or indirect interaction

Cited by 23 publications

References 34 publications

Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti‐inflammatory purinergic signalling in activated NK cells

Human dental pulp stem cells regulate allogeneic NK cells’ function via induction of anti‐inflammatory purinergic signalling in activated NK cells

Inflammation in tissue engineering: The Janus between engraftment and rejection

Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

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