TGF-β engineered mesenchymal stem cells (TGF-β/MSCs) for treatment of Type 1 diabetes (T1D) mice model

Daneshmandi, Saeed; Karimi, Mohammad Hossein; Pourfathollah, Ali Akbar

doi:10.1016/j.intimp.2017.01.019

Cited by 35 publications

(20 citation statements)

References 30 publications

(32 reference statements)

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“…Mesenchymal stem cells (MSCs) hold great promise for the treatment of multiple diseases and disorders. 1,2 Although MSCs are capable of high levels of ex vivo expansion and are already in clinical use for numerous applications, 3-5 a significant challenge remains in their efficient delivery to target locations in order to enhance successful engraftment. 6 This limitation is mainly evident when the therapeutic application requires MSCs to secrete factors immediately following injection.…”

Section: Introductionmentioning

confidence: 99%

Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites

Li¹,

Wei²,

Lv³

et al. 2019

IJN

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BackgroundDeveloping new methods to deliver cells to the injured tissue is a critical factor in translating cell therapeutics research into clinical use; therefore, there is a need for improved cell homing capabilities.Materials and methodsIn this study, we demonstrated the effects of labeling rat bone marrow-derived mesenchymal stem cells (MSCs) with fabricated polydopamine (PDA)-capped Fe3O4 (Fe3O4@PDA) superparticles employing preassembled Fe3O4 nanoparticles as the cores.ResultsWe found that the Fe3O4@PDA composite superparticles exhibited no adverse effects on MSC characteristics. Moreover, iron oxide nanoparticles increased the number of MSCs in the S-phase, their proliferation index and migration ability, and their secretion of vascular endothelial growth factor relative to unlabeled MSCs. Interestingly, nanoparticles not only promoted the expression of C-X-C chemokine receptor 4 but also increased the expression of the migration-related proteins c-Met and C-C motif chemokine receptor 1, which has not been reported previously. Furthermore, the MSC-loaded nanoparticles exhibited improved homing and anti-inflammatory abilities in the absence of external magnetic fields in vivo.ConclusionThese results indicated that iron oxide nanoparticles rendered MSCs more favorable for use in injury treatment with no negative effects on MSC properties, suggesting their potential clinical efficacy.

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Section: Introductionmentioning

confidence: 99%

Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites

Li¹,

Wei²,

Lv³

et al. 2019

IJN

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“…This IFN-c:TGF-b signaling loop was used by Daneshmandi et al who engineered TGF-b overexpressing MSCs to treat diabetes type 1 [29]. In animal model of diabetes, TGF-b engineered MSCs induced polarization of immune response from proinflammatory Th1 towards anti-inflammatory Th2 which resulted with increased serum levels of insulin and improved survival of diabetic mice [29]. In accordance with these findings, results obtained in recently conducted clinical trial showed that transplantation of 1.1 million UC-MSCs/kg combined with 106.8 million BM-mononuclear cells/kg was associated with moderate improvement of metabolic measures in patients with established diabetes type 1 [30].…”

Section: Tgf-bmentioning

confidence: 99%

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

et al. 2017

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Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed. Under inflammatory conditions, MSCs-derived factors suppress both innate and adaptive immunity by attenuating maturation and capacity for antigen presentation of dendritic cells, by inducing polarization of macrophages towards alternative phenotype, by inhibiting activation and proliferation of T and B lymphocytes and by reducing cytotoxicity of NK and NKT cells. In this review, we emphasized current findings regarding immuno-modulatory effects of MSC-derived factors and emphasize their potential in the therapy of immune-mediated diseases. © 2017 BioFactors, 43(5):633-644, 2017.

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“…Increasing number of recent studies demonstrate that humans MSCs are well tolerated and functional in regenerative and in ammatory mouse models. [94][95][96][97] Therefore, we chose to perform our investigations by studying the interaction between human MSCs and mice T cells in order to test later their immunological properties in highly in ammatory xenogeneic mice model. We rst con rmed that although FL and BM-MSCs share several common characteristics, including a spindleshaped broblast-like morphology, phenotype and differentiation capacities, FL-MSCs bore an outstanding ex vivo expansion ability compared to adult BM-MSCs.…”

Section: Discussionmentioning

confidence: 99%

Human Fetal Liver MSCs are More Effective Than Adult Bone Marrow MSCs for Their Immunosuppressive, Immunomodulatory and Foxp3+ T regs Induction Capacity

Valderrama

Han

et al. 2020

Preprint

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Abstract Background: Mesenchymal stem cells (MSCs) display active capacities of suppressing or modulating harmful immune responses through diverse molecular mechanisms. These cells are under extensive translational efforts as cell therapies for immune-mediated diseases and transplantations. A wide range of preclinical studies and limited number of clinical trials using MSCs have not only shown promising safety and efficacy profiles but have also revealed changes in regulatory T cell (T reg) frequency and function. However, the mechanisms underlying this important observation are not well understood. Cell-to-cell contact, production of soluble factors, reprogramming of antigen presenting cells to tolerogenic phenotypes have emerged as possible mechanisms by which MSCs produce an immunomodulatory environment for T reg expansion. We and others demonstrated that adult bone-marrow (BM)-MSCs suppress adaptive immune responses directly by inhibiting the proliferation of CD4+ (“helper”) and CD8+ (“cytotoxic”) T cells but also indirectly through induction of Tregs. In parallel we demonstrated that fetal liver (FL)-MSCs displays much longer-lasting immunomodulatory properties compared to BM-MSCs, by inhibiting directly the proliferation and activation of CD4+ and CD8+ T cells. Therefore, we investigated if FL-MSCs exert their strong immunosuppressive effect also indirectly through induction of T regs.Methods: MSCs were obtained from FL and adult BM and characterized according to their surface antigen expression, their multilineage differentiation and their proliferation potential. Using different in-vitro combinations, we performed co-cultures of FL or BM-MSCs and murine CD3+CD25-T cells to investigate immunosuppressive effects of MSCs on T cells and to quantify their capacity to induce functional T regs. Results: We demonstrated that although both types of MSC exhibit similar phenotype profile and differentiation capacity, FL-MSCs have significantly higher proliferative capacity and ability to suppress both CD4+ and CD8+ murine T cell proliferation and to modulate them towards less active phenotypes than adult BM-MSCs. Moreover, their substantial suppressive effect was associated with an outstanding increase of functional CD4+CD25+Foxp3+ T regs compared to BM-MSCs.Conclusions: These results highlight the immunosuppressive activity of FL-MSCs on T cells and show for the first time that one of the main immunoregulatory mechanisms of FL-MSCs passes through active and functional T reg induction.

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TGF-β engineered mesenchymal stem cells (TGF-β/MSCs) for treatment of Type 1 diabetes (T1D) mice model

Abstract: Engineered TGF-β/MSCs could restore some T1D features, including the regulation of adverse immune responses and could be potent tools for cell therapy of T1D comparing MSCs alone.

Cited by 35 publications

References 30 publications

Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites

Iron oxide nanoparticles promote the migration of mesenchymal stem cells to injury sites

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

Human Fetal Liver MSCs are More Effective Than Adult Bone Marrow MSCs for Their Immunosuppressive, Immunomodulatory and Foxp3+ T regs Induction Capacity

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