Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable encapsulating the anticancer drug doxorubicin (DOX) with high loading (22.1% w/w). The release DOX from DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent...

Abstract Due to the unsatisfied effects of clinical drugs used in rheumatoid arthritis (RA), investigators shifted their focus on biotherapy. Although human gingival mesenchymal stem cells (GMSC) have potential be treating RA, GMSC‐based therapy has some inevitable side such as immunogenicity and tumorigenicity. As one most important paracrine mediators, GMSC‐derived exosomes (GMSC‐Exo) exhibit therapeutic via immunomodulation a variety disease models, bypassing shortcomings direct use MSCs....

Thymopoiesisis regulated by the thymic microenvironment, of which epithelial cells are major components. Both cortical and medullary (TECs) have been shown to arise from a common progenitor cell. Here we show for first time that mouse embryonic stem (mESCs) can be selectively induced in vitro differentiate into phenotype progenitors (TEPs). When placed vivo, these mESC-derived TEPs self-renew, develop TECs, reconstitute normal architecture. Functionally, ESC-derived enhanced thymocyte...

Abstract Background The WNT/β-CATENIN signaling cascade is crucial for the patterning of early lung morphogenesis in mice, but its role developing human remains to be determined. In this study, expression patterns canonical components, including WNT ligands ( WNT2 , WNT7B ), receptors FZD4 FZD7 LRP5 LRP6 transducers DVL2 DVL3 GSK-3β β-CATENIN APC AXIN2 transcription factors TCF4 LEF1 ) and antagonists SOSTDC1 were examined embryonic at 7, 12, 17 21 weeks gestation (W) by real-time qRT-PCR...

Abstract Thymic epithelial cells (TECs) are the major components of thymic microenvironment for T cell development. TECs derived from progenitors (TEPs). It has been reported that human ESCs (hESCs) can be directed to differentiate into TEPs in vitro . However, efficiency differentiation is low. Furthermore, transplantation hESC-TEPs mice only resulted a very low level development co-transplanted hematopoietic precursors. We show here we have developed novel protocol efficiently induce hESCs...

ABSTRACT Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disease (AID) mediated by myelin‐reactive CD4 + T cells. Experimental encephalomyelitis (EAE) widely used animal model of human MS. Erythrocyte membrane‐associated protein (ERMAP) novel erythrocyte‐specific adhesion/receptor molecule associated with erythrocyte adhesion. We have previously characterised it as inhibitory immune checkpoint and demonstrated that recombinant ERMAP proteins ameliorate EAE; however, the...

Bone marrow transplantation (BMT) is often followed by a prolonged period of T cell deficiency. Therefore, the enhancement reconstitution an important clinical goal. We have identified novel hybrid cytokine containing IL-7 and β-chain hepatocyte growth factor (HGF) in supernatant cultured mouse BM stromal cells. cloned expressed IL-7/HGFβ gene to produce single-chain rIL-7/HGFβ protein that stimulates vitro proliferation thymocytes, early B-lineage cell, day 12 spleen CFUs. In this study, we...

We have reported that in vivo administration of the hybrid cytokine rIL-7/HGFβ or rIL-7/HGFα, which contains interleukin-7 (IL-7) and β- α-chain hepatocyte growth factor (HGF), significantly enhances thymopoiesis mice after bone marrow transplantation. shown HGF receptor, c-Met, is involved effect cytokines. To address role c-Met signalling thymocyte development recovery, we generated conditional knockout (cKO) was specifically deleted T cells by crossing c-Met(ft/ft) with CD4-Cre transgenic...

BackgroundThymus hypoplasia due to stromal cell problems has been linked mutations in several transcription factors, including Forkhead box N1 (FOXN1). FOXN1 supports T-cell development by regulating the formation and expansion of thymic epithelial cells (TECs). While autosomal recessive result a nude severe combined immunodeficiency phenotype, impact single-allelic or compound heterozygous is less well-defined.ObjectiveWith more than 400 reported, their on protein function thymopoiesis...

The T-box transcriptional factor (Tbx) family of factors has distinct roles in a wide range embryonic differentiation or response pathways. Tbx1, transcription factor, is an important gene for the human congenital disorder 22q11.2 deletion syndrome. Induced pluripotent stem cell (iPSC) technology offers new opportunities both elucidation pathogenesis diseases and development stem-cell-based therapies. In this study, we generated iPSCs from Tbx1(-/-) Tbx1(+/+) fibroblasts investigated...

Abstract Both IL7 and IL15 have become important candidate immunomodulators for cancer treatment. However, or used alone suffers from shortcomings, such as short serum half-life limited antitumor effect. We cloned expressed a recombinant (r) IL7/IL15 fusion protein in which are linked by flexible linker. then compared the effect of rIL7/IL15 with individual factors rIL7 and/or rIL15. show here that has higher activity than combination both murine B16F10 melanoma CT-26 colon models. This was...

Difficulty obtaining sufficient hematopoietic stem cells (HSCs) directly from the donor has limited clinical use of HSC transplantation. Numerous attempts to stimulate ex vivo growth purified HSCs with cytokines and factors generally have induced only modest increases in numbers while decreasing their reconstituting ability. We previously developed a recombinant single-chain form naturally occurring murine hybrid cytokine IL-7 β chain hepatocyte factor (rIL-7/HGFβ) that stimulates vitro...

A prolonged period of T-cell recovery is the major challenge in hematopoietic stem cell transplantation (HSCT). Thymic epithelial cells (TECs) are component thymic microenvironment for generation. However, TECs undergo degeneration over time. FOXN1 plays a critical role TEC development and required to maintain adult thymopoiesis. To investigate potential application FOXN1, we have cloned expressed recombinant protein (rFOXN1) that was fused with cell-penetrating peptides. We show here rFOXN1...

Abstract Pre-pro-B cell growth-stimulating factor (PPBSF) is a heterodimer of IL-7 and 30-kDa cofactor. Unlike monomeric IL-7, PPBSF selectively induces proliferation differentiation pre-pro-B cells up-regulates IL-7Rα-chain expression. Here we clone the cofactor from bone marrow stromal identify it as variant β-chain hepatocyte growth (HGF), pleiotropic cytokine homologous to plasminogen that regulates growth, motility, morphogenesis. We further demonstrate that, in presence low m.w....

T cell immunodeficiency is a major complication of bone marrow (BM) transplantation (BMT). Therefore, approaches to enhance reconstitution after BMT are required. We have purified hybrid cytokine, consisting IL-7 and the β-chain hepatocyte growth factor (HGFβ) (IL-7/HGFβ), from unique long-term BM culture system. cloned expressed IL-7/HGFβ gene in which HGFβ genes connected by flexible linker generate rIL-7/HGFβ protein. Here, we show that treatment enhances thymopoiesis allogeneic BMT....

The immune cytokine interleukin (IL)-7 and the β-chain of hepatocyte growth factor (HGF) aggregate to form a naturally occurring heterodimer that stimulates common lymphoid progenitors immature B T cells. We have cloned expressed as single-chain hybrid [recombinant (r) IL-7/HGFβ], which short-term hematopoietic stem cells well precursors. Inasmuch IL-7 HGF are known antitumor protumor activities, respectively, we determined here whether either these activities is exhibited by rIL-7/HGFβ....

Alzheimer's disease (AD) is a devastating neurodegenerative disorder and the most common cause of dementia in elderly. Although amyloid-beta (Aβ) plaque deposition chronic neuroinflammation central nervous system (CNS) contribute to AD pathology, neither Aβ removal nor anti-inflammatory therapy has shown much clinical success, suggesting that combinational therapies for disease-causative factors may be needed amelioration. Recent data also suggest systemic immunity should boosted, rather...

T cell responses are fine-tuned by co-stimulatory and co-inhibitory molecules. Among the regulators, B7 family members of central importance. The recent success in targeting molecules for treatment immune-related diseases has attracted intense interest identifying additional B7-related In this study, we describe CD300c as a novel molecule that shares significant sequence homology with existing members. protein is expressed on professional antigen-presenting cells (APC), including B cells,...