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Kazuko Ino Masahiro Masuya Isao Tawara Eri Miyata Keiko Oda Yoshiki Nakamori Kei Suzuki Kohshi Ohishi Naoyuki Katayama 《PloS one》2014,9(1)
Recent studies have shown that monocytes possess pluripotent plasticity. We previously reported that monocytes could differentiate into hepatic stellate cells. Although stellate cells are also present in the pancreas, their origin remains unclear. An accumulation of enhanced green fluorescent protein (EGFP)+CD45– cells was observed in the pancreases and livers of chimeric mice, which were transplanted with a single hematopoietic stem cell isolated from EGFP-transgenic mice and treated with carbon tetrachloride (CCl4). Because the vast majority of EGFP+CD45– cells in the pancreas expressed stellate cell-associated antigens such as vimentin, desmin, glial fibrillary acidic protein, procollagen-I, and α-smooth muscle actin, they were characterized as pancreatic stellate cells (PaSCs). EGFP+ PaSCs were also observed in CCl4-treated mice adoptively transferred with monocytes but not with other cell lineages isolated from EGFP-transgenic mice. The expression of monocyte chemoattractant protein-1 (MCP-1) and angiotensin II (Ang II) increased in the pancreas of CCl4-treated mice and their respective receptors, C-C chemokine receptor 2 (CCR2) and Ang II type 1 receptor (AT1R), were expressed on Ly6Chigh monocytes isolated from EGFP-transgenic mice. We examined the effect of an AT1R antagonist, irbesartan, which is also a CCR2 antagonist, on the migration of monocytes into the pancreas. Monocytes migrated toward MCP-1 but not Ang II in vitro. Irbesartan inhibited not only their in vitro chemotaxis but also in vivo migration of adoptively transferred monocytes from peripheral blood into the pancreas. Irbesartan treatment significantly reduced the numbers of EGFP+F4/80+CCR2+ monocytic cells and EGFP+ PaSCs in the pancreas of CCl4-treated chimeric mice receiving EGFP+ bone marrow cells. A specific CCR2 antagonist RS504393 inhibited the occurrence of EGFP+ PaSCs in injured mice. We propose that CCR2+ monocytes migrate into the pancreas possibly via the MCP-1/CCR2 pathway and give rise to PaSCs. 相似文献
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Bone‐marrow‐derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats
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Jing Zhou Liyan Jiang Xuan Long Cuiping Fu Xiangdong Wang Xiaodan Wu Zilong Liu Fen Zhu Jindong Shi Shanqun Li 《Journal of cellular and molecular medicine》2016,20(9):1706-1717
Gastric aspiration lung injury is one of the most common clinical events. This study investigated the effects of bone‐marrow‐derived mesenchymal stem cells (BMSCs) on combined acid plus small non‐acidified particle (CASP)‐induced aspiration lung injury. Enhanced green fluorescent protein (EGFP+) or EGFP? BMSCs or 15d‐PGJ2 were injected via the tail vein into rats immediately after CASP‐induced aspiration lung injury. Pathological changes in lung tissues, blood gas analysis, the wet/dry weight ratio (W/D) of the lung, levels of total proteins and number of total cells and neutrophils in bronchoalveolar lavage fluid (BALF) were determined. The cytokine levels were measured using ELISA. Protein expression was determined by Western blot. Bone‐marrow‐derived mesenchymal stem cells treatment significantly reduced alveolar oedema, exudation and lung inflammation; increased the arterial partial pressure of oxygen; and decreased the W/D of the lung, the levels of total proteins and the number of total cells and neutrophils in BALF in the rats with CASP‐induced lung injury. Bone‐marrow‐derived mesenchymal stem cells treatment decreased the levels of tumour necrosis factor‐α and Cytokine‐induced neutrophil chemoattractant (CINC)‐1 and the expression of p‐p65 and increased the levels of interleukin‐10 and 15d‐PGJ2 and the expression of peroxisome proliferator‐activated receptor (PPAR)‐γ in the lung tissue in CASP‐induced rats. Tumour necrosis factor‐α stimulated BMSCs to secrete 15d‐PGJ2. A tracking experiment showed that EGFP+ BMSCs were able to migrate to local lung tissues. Treatment with 15d‐PGJ2 also significantly inhibited CASP‐induced lung inflammation and the production of pro‐inflammatory cytokines. Our results show that BMSCs can protect lung tissues from gastric aspiration injury and inhibit lung inflammation in rats. A beneficial effect might be achieved through BMSC‐derived 15d‐PGJ2 activation of the PPAR‐γ receptor, reducing the production of proinflammatory cytokines. 相似文献
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Ewa K. Zuba‐Surma Yiru Guo Hisham Taher Santosh K. Sanganalmath Greg Hunt Robert J. Vincent Magda Kucia Ahmed Abdel‐Latif Xian‐Liang Tang Mariusz Z. Ratajczak Buddhadeb Dawn Roberto Bolli 《Journal of cellular and molecular medicine》2011,15(6):1319-1328
Adult bone marrow‐derived very small embryonic‐like stem cells (VSEL‐SCs) exhibit a Sca‐1+/Lin–/CD45– phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 106) of freshly isolated, non‐expanded VSEL‐SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL‐SCs in the marrow is very low, we examined whether VSEL‐SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30 min. coronary occlusion followed by reperfusion and, 48 hrs later, received an intramyocardial injection of vehicle (group I, n= 11), 1 × 105 enhanced green fluorescent protein (EGFP)‐labelled expanded untreated VSEL‐SCs (group II, n= 7), or 1 × 105 EGFP‐labelled expanded VSEL‐SCs pre‐incubated in a cardiogenic medium (group III, n= 8). At 35 days after myocardial infarction (MI), mice treated with pre‐incubated VSEL‐SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle‐treated controls. In contrast, transplantation of expanded but untreated VSEL‐SCs did not produce appreciable reparative benefits. Scattered EGFP+ cells expressing α‐sarcomeric actin, platelet endothelial cell adhesion molecule (PECAM)‐1, or von Willebrand factor were present in VSEL‐SC‐treated mice, but their numbers were very small. No tumour formation was observed. We conclude that VSEL‐SCs expanded in culture retain the ability to alleviate LV dysfunction and remodelling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such pre‐incubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results support the potential therapeutic utility of VSEL‐SCs for cardiac repair. 相似文献
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Xiahui Ge Chong Bai Jianming Yang Guoliang Lou Qiang Li Ruohua Chen 《Journal of cellular biochemistry》2013,114(7):1595-1605
Previous studies proved that bone marrow‐derived mesenchymal stem cells (BMSCs) could improve a variety of immune‐mediated disease by its immunomodulatory properties. In this study, we investigated the effect on airway remodeling and airway inflammation by administrating BMSCs in chronic asthmatic mice. Forty‐eight female BALB/c mice were randomly distributed into PBS group, BMSCs treatment group, BMSCs control group, and asthmatic group. The levels of cytokine and immunoglobulin in serum and bronchoalveolar lavage fluid were detected by enzyme‐linked immunosorbent assay. The number of CD4+CD25+regulatory T cells and morphometric analysis was determined by flow cytometry, hematoxylin‐eosin, immunofluorescence staining, periodic‐acid Schiff, and masson staining, respectively. We found that airway remodeling and airway inflammation were evident in asthmatic mice. Moreover, low level of IL‐12 and high levels of IL‐13, IL‐4, OVA‐specific IgG1, IgE, and IgG2a and the fewer number of CD4+CD25+regulatory T cells were present in asthmatic group. However, transplantation of BMSCs significantly decreased airway inflammation and airway remodeling and level of IL‐4, OVA‐specific IgE, and OVA‐specific IgG1, but elevated level of IL‐12 and the number of CD4 + CD25 + regulatory T cells in asthma (P < 0.05). However, BMSCs did not contribute to lung regeneration and had no significant effect on levels of IL‐10, IFN‐Y, and IL‐13. In our study, BMSCs engraftment prohibited airway inflammation and airway remodeling in chronic asthmatic group. The beneficial effect of BMSCs might involved the modulation imbalance cytokine toward a new balance Th1–Th2 profiles and up‐regulation of protective CD4 + CD25 + regulatory T cells in asthma, but not contribution to lung regeneration. J. Cell. Biochem. 114: 1595–1605, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
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Human umbilical CD34+ immature haematopoietic cells were rapidly and efficiently obtained from light density MNC (mononuclear cells) by MACS (magnetic cell sorting). An ex vivo expanded population of CD34+ was cultured in serum‐free medium supplemented with cytokines FL (flt3 ligand), SCF (stem cell factor) and TPO (thrombopoietin) in order to obtain a sufficient number of CD34+ cells. CD34+ cells expanded from cord blood for 7 days were demonstrated to increase in the absolute number of CD34+ cells by 5.12±2.47‐fold (mean±S.D., n=3). Flow cytometric analysis demonstrated that the percentage of CD34 antigen expression after expansion of the culture was 97.81±1.07%, whereas it was 69.39±10.37% in none‐expanded CD34+ cells (mean±S.D., n=3), thus defining a system that allowed extensive amplification accompanied by no maturation. MTs (metallothioneins), low molecular weight, cysteine‐rich metal‐binding proteins, exhibit various functions, including metal detoxification and homoeostasis. We here examined the expression pattern of functional members of the MT gene family in immature CD34+ cells and compared it with more mature CD34? cells in order to strengthen the proposed function of MT in differentiation. Cells were cultured in RPMI 1640 medium, with or without different zinc supplements for 24 h. Relative quantitative expression of MT isogenes in the mature CD34? cells was higher than in the immature CD34+ cells. IHC (immunohistochemical staining) revealed an increased MT protein biosynthesis in CD34? cells, greater than in CD34+ cells. Therefore, the role of MT in differentiation of human haematopoietic progenitor cells from human cord blood is reported for the first time. 相似文献
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Bone marrow mesenchymal stem cells (BMSCs) have the ability of self-renewal and multi-directional differentiation. Recent
reports showed that BMSCs could differentiate into endocrine cells of pancreas. However, the differentiation is not efficient
enough to produce insulin-producing cells for the future therapeutic use. Pdx-1 is a crucial regulator for pancreatic development. Therefore we constructed a eukaryotic expression vector containing Pdx-1 to determine the effect of Pdx-1 expression on differentiation of BMSCs in vitro. The results showed that BMSCs could self-assemble to form functional pancreatic islet-like structures after differentiation
in vitro. The proportion of insulin-producing cells differentiated from Pdx-1+BMSCs was 28.23%±2.56%, higher than that from BMSCs transfected with vacant vector and Pdx-1 − BMSCs (7.23%±1.56% and 4.08%±2.69% respectively) by flow cytometry. Immunocytochemical examination also testified the expression
of multiple β-cells-specific genes such as insulin, glucagons, somatostatin in differentiated BMSCs. The results also revealed
that the expressions of genes mentioned above in Pdx-1+BMSCs were higher than that in Pdx-1−BMSCs, which was confirmed by Western blotting analysis and RT-PCR. Glucose-induced insulin secretion from Pdx-1+BMSCs in 5mmol/L and 25mmol/L glocuse was (56.61±4.82) μU/mL and (115.29±2.56) μU/mL respectively, which were much higher
than those from Pdx-1−BMSCs((25.53±6.49) μU/mL and (53.26±7.56) μU/mL respectively). Grafted animals were able to maintain their body weight and
survive for relatively longer periods of time than hyperglycemic sham-grafted controls, which demonstrated an overall beneficial
effect of the grafted cells on the health of the animals. These findings thus suggested that exogenous expression of Pdx-1 should provide a promising approach for efficiently producing islet-like cells from BMSCs for the future therapeutic use
in diabetic patients. 相似文献
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Hidetaka Murai Ryosuke Tadokoro Ken‐Ichiro Sakai Yoshiko Takahashi 《Development, growth & differentiation》2015,57(3):232-241
During skin pigmentation in avians and mammalians, melanin is synthesized in the melanocytes, and subsequently transferred to adjacently located keratinocytes, leading to a wide coverage of the body surface by melanin‐containing cells. The behavior of melanocytes is influenced by keratinocytes shown mostly by in vitro studies. However, it has poorly been investigated how such intercellular cross‐talk is regulated in vivo because of a lack of suitable experimental models. Using chicken embryos, we developed a method that enables in vivo gene manipulations of melanocytes and keratinocytes, where these cells are separately labeled by different genes. Two types of gene transfer techniques were combined: one was a retrovirus‐mediated gene infection into the skin/keratinocytes, and the other was the in ovo DNA electroporation into neural crest cells, the origin of melanocytes. Since the Replication‐Competent Avian sarcoma‐leukosis virus long terminal repeat with Splice acceptor (RCAS) infection was available only for the White leghorn strain showing little pigmentation, melanocytes prepared from the Hypeco nera (pigmented) were back‐transplanted into embryos of White leghorn. Prior to the transplantation, enhanced green fluorescent protein (EGFP)+Neor+‐electroporated melanocytes from Hypeco nera were selectively grown in G418‐supplemented medium. In the skin of recipient White leghorn embryos infected with RCAS‐mOrange, mOrange+ keratinocytes and transplanted EGFP+ melanocytes were frequently juxtaposed each other. High‐resolution confocal microscopy also revealed that transplanted melanocytes exhibited normal behaviors regarding distribution patterns of melanocytes, dendrite morphology, and melanosome transfer. The method described in this study will serve as a useful tool to understand the mechanisms underlying intercellular regulations during skin pigmentation in vivo. 相似文献
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Sidan Li Qiongli Zhai Dehui Zou Hengxing Meng Zhenqing Xie Changhong Li Yafei Wang Junyuan Qi Tao Cheng Lugui Qiu 《Journal of cellular physiology》2013,228(5):1002-1009
The majority of hematopoietic stem/progenitor cells (HSPCs) reside in bone marrow (BM) surrounded by a specialized environment, which governs HSPC function. Here we investigated the potential role of bone remodeling cells (osteoblasts and osteoclasts) in homeostasis and stress‐induced HSPC mobilization. Peripheral blood (PB) and BM in steady/mobilized state were collected from healthy donors undergoing allogeneic transplantation and from mice treated with granulocyte colony stimulating factor (G‐CSF), parathyroid hormone (PTH), or receptor activator of nuclear factor kappa‐B ligand (RANKL). The number and the functional markers of osteoblasts and osteoclasts were checked by a series of experiments. Our data showed that the number of CD45?Ter119? osteopontin (OPN)+ osteoblasts was significantly reduced from 4,085 ± 135 cells/femur on Day 0 to 1,032 ± 55 cells/femur on Day 5 in mice (P = 0.02) and from 21.38 ± 0.66 on Day 0 to 14.78 ± 0.65 on Day 5 in healthy donors (P < 0.01). Decrease of osteoblast number leads to reduced level of HSPC mobilization regulators stromal cell‐derived factor‐1 (SDF‐1), stem cell factor (SCF), and OPN. The osteoclast number at bone surface (OC.N/B.s) was significantly increased from 1.53 ± 0.12 on Day 0 to 4.42 ± 0.46 on Day 5 (P < 0.01) in G‐CSF‐treated mice and from 0.88 ± 0.20 on Day 0 to 3.24 ± 0.31 on Day 5 (P < 0.01) in human. Serum TRACP‐5b level showed a biphasic trend during G‐CSF treatment. The ratio of osteoblasts number per bone surface (OB.N/B.s) to OC.N/B.s was changed after adding PTH plus RANKL during G‐CSF treatment. In conclusion, short term G‐CSF treatment leads to reduction of osteoblasts and stimulation of osteoclasts, and interrupting bone remodeling balance may contribute to HSPC mobilization. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc. 相似文献
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Yan Zhou Dan Han Taylor Follansbee Xuesong Wu Sebastian Yu Bo Wang Zhenrui Shi Dan T. Domocos Mirela Carstens Earl Carstens Samuel T. Hwang 《Journal of cellular and molecular medicine》2019,23(7):4819-4828
Transient receptor potential ankyrin 1 (TRPA1), a membrane protein ion channel, is known to mediate itch and pain in skin. The function of TRPA1, however, in psoriasiform dermatitis (PsD) is uncertain. Herein, we found that expression of TRPA1 is highly up‐regulated in human psoriatic lesional skin. To study the role of TRPA1 in PsD, we assessed Psoriasis Severity Index (PSI) scores, transepidermal water loss (TEWL), skin thickness and pathology, and examined dermal inflammatory infiltrates, Th17‐related genes and itch‐related genes in c57BL/6 as wild‐type (WT) and TRPA1 gene knockout (KO) mice following daily application of topical IMQ cream for 5 days. Compared with WT mice, clinical scores, skin thickness change and TEWL scores were similar on day 3, but were significantly decreased on day 5 in IMQ‐treated TRPA1 KO mice (vs WT mice), suggesting reduced inflammation and skin barrier defects. Additionally, the relative area of epidermal Munro's microabscesses and mRNA levels of neutrophil inducible chemokines (S100A8, S100A9 and CXCL1) were decreased in the treated skin of TRPA1 KO mice, suggesting that neutrophil recruitment was impaired in the KO mice. Furthermore, mast cells, CD31+ blood vascular cells, CD45+ leukocytes and CD3+ T cells were all reduced in the treated skin of TRPA1 KO mice. Lastly, mRNA expression levels of IL‐1β, IL‐6, IL‐23, IL‐17A, IL‐17F and IL‐22 were decreased in TRPA1 KO mice. In summary, these results suggest a key role for TRPA1 in psoriasiform inflammation and raising its potential as a target for therapeutic intervention. 相似文献
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Andrade PZ da Silva CL dos Santos F Almeida-Porada G Cabral JM 《Journal of cellular biochemistry》2011,112(7):1822-1831
Since umbilical cord blood (UCB), contains a limited hematopoietic stem/progenitor cells (HSC) number, successful expansion protocols are needed to overcome the hurdles associated with inadequate numbers of HSC collected for transplantation. UCB cultures were performed using a human stromal‐based serum‐free culture system to evaluate the effect of different initial CD34+ cell enrichments (Low: 24 ± 1.8%, Medium: 46 ± 2.6%, and High: 91 ± 1.5%) on the culture dynamics and outcome of HSC expansion. By combining PKH tracking dye with CD34+ and CD34+CD90+ expression, we have identified early activation of CD34 expression on CD34? cells in Low and Medium conditions, prior to cell division (35 ± 4.7% and 55 ± 4.1% CD34+ cells at day 1, respectively), affecting proliferation/cell cycle status and ultimately determining CD34+/CD34+CD90+ cell yield (High: 14 ± 1.0/3.5 ± 1.4‐fold; Medium:22 ± 2.0/3.4 ± 1,0‐fold; Low:31 ± 3.0/4.4 ± 1.5‐fold) after a 7‐day expansion. Considering the potential benefits of using expanded UCB HSC in transplantation, here we quantified in single UCB units, the impact of using one/two immunomagnetic sorting cycles (corresponding to Medium and High initial progenitor content), and the average CD34+ cell recovery for each strategy, on overall CD34+ cell expansion. The higher cell recovery upon one sorting cycle lead to higher CD34+ cell numbers after 7 days of expansion (30 ± 2.0 vs. 13 ± 1.0 × 106 cells). In particular, a high (>90%) initial progenitor content was not mandatory to successfully expand HSC, since cell populations with moderate levels of enrichment readily increased CD34 expression ex‐vivo, generating higher stem/progenitor cell yields. Overall, our findings stress the importance of establishing a balance between the cell proliferative potential and cell recovery upon purification, towards the efficient and cost‐effective expansion of HSC for cellular therapy. J. Cell. Biochem. 112: 1822–1831, 2011. © 2011 Wiley‐Liss, Inc. 相似文献
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Background
The aim of this study was to investigate gene transfer to human umbilical cord blood (CB) CD34+/CD38low and NOD/SCID repopulating cells using oncoretroviral vectors and to compare the transduction efficiency using three different viral envelopes.Methods
CB cells were transduced on Retronectin using an MSCV‐based vector with the gene for GFP (MGIN), which was packaged into three different cell lines giving different envelopes: PG13‐MGIN (GALV), 293GPG‐MGIN (VSV‐G) or AM12‐MGIN (amphotropic).Results
Sorted CD34+/CD38low cells were efficiently transduced after 3 days of cytokine stimulation and the percentage of GFP‐positive cells was 61.8±6.6% (PG13‐MGIN), 26.9±3.5% (293GPG‐MGIN), and 39.3±4.8% (AM12‐MGIN). For transplantation experiments, CD34+ cells were pre‐stimulated for 2 days before transduction on Retronectin preloaded with vector and with the addition of 1/10th volume of viral supernatant on day 3. On day 4, the expanded equivalent of 2.5×105 cells was injected into irradiated NOD/SCID mice. All three pseudotypes transduced NOD/SCID repopulating cells (SRCs) equally well in the presence of serum, but engraftment was reduced when compared with freshly thawed cells. Simultaneous transduction with all three vector pseudotypes increased the gene transfer efficiency to SRCs but engraftment was significantly impaired. There were difficulties in producing amphotropic vectors at high titers in serum‐free medium and transduction of CD34+ cells using VSV‐G‐pseudotyped vectors under serum‐free conditions was very inefficient. In contrast, transduction with PG13‐MGIN under serum‐free conditions resulted in the maintenance of SRCs during transduction, high levels of engraftment (29.3±6.6%), and efficient gene transfer to SRCs (46.2±4.8%).Conclusions
The best conditions for transduction and engraftment of CB SRCs were obtained with GALV‐pseudotyped vectors using serum‐free conditions. Copyright © 2002 John Wiley & Sons, Ltd.15.
Hagar I. Labouta Martina Hampel Sibylle Thude Katharina Reutlinger Karl‐Heinz Kostka Marc Schneider 《Journal of biophotonics》2012,5(1):85-96
Multiphoton microscopy has become popular in studying dermal nanoparticle penetration. This necessitates studying the imaging parameters of multiphoton microscopy in skin as an imaging medium, in terms of achievable detection depths and the resolution limit. This would simulate real‐case scenarios rather than depending on theoretical values determined under ideal conditions. This study has focused on depth profiling of sub‐resolution gold nanoparticles (AuNP) in reconstructed (fixed and unfixed) and human skin using multiphoton microscopy. Point spread functions (PSF) were determined for the used water‐immersion objective of 63×/NA = 1.2. Factors such as skin‐tissue compactness and the presence of wrinkles were found to deteriorate the accuracy of depth profiling. A broad range of AuNP detectable depths (20–100 μm) in reconstructed skin was observed. AuNP could only be detected up to ~14 μm depth in human skin. Lateral (0.5 ± 0.1 μm) and axial (1.0 ± 0.3 μm) PSF in reconstructed and human specimens were determined. Skin cells and intercellular components didn't degrade the PSF with depth. In summary, the imaging parameters of multiphoton microscopy in skin and practical limitations encountered in tracking nanoparticle penetration using this approach were investigated. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
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Min Kim Naomi R. Truong Virginia James Lidija Bosnjak Kerrie J. Sandgren Andrew N. Harman Najla Nasr Kirstie M. Bertram Norman Olbourne Shailandra Sawleshwarkar Kaylene McKinnon Ralph C. Cohen Anthony L. Cunningham 《PLoS pathogens》2015,11(4)
The mechanism by which immunity to Herpes Simplex Virus (HSV) is initiated is not completely defined. HSV initially infects mucosal epidermis prior to entering nerve endings. In mice, epidermal Langerhans cells (LCs) are the first dendritic cells (DCs) to encounter HSV, but it is CD103+ dermal DCs that carry viral antigen to lymph nodes for antigen presentation, suggesting DC cross-talk in skin. In this study, we compared topically HSV-1 infected human foreskin explants with biopsies of initial human genital herpes lesions to show LCs are initially infected then emigrate into the dermis. Here, LCs bearing markers of maturation and apoptosis formed large cell clusters with BDCA3+ dermal DCs (thought to be equivalent to murine CD103+ dermal DCs) and DC-SIGN+ DCs/macrophages. HSV-expressing LC fragments were observed inside the dermal DCs/macrophages and the BDCA3+ dermal DCs had up-regulated a damaged cell uptake receptor CLEC9A. No other infected epidermal cells interacted with dermal DCs. Correspondingly, LCs isolated from human skin and infected with HSV-1 in vitro also underwent apoptosis and were taken up by similarly isolated BDCA3+ dermal DCs and DC-SIGN+ cells. Thus, we conclude a viral antigen relay takes place where HSV infected LCs undergo apoptosis and are taken up by dermal DCs for subsequent antigen presentation. This provides a rationale for targeting these cells with mucosal or perhaps intradermal HSV immunization. 相似文献
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Wu Y Ren M Yang R Liang X Ma Y Tang Y Huang L Ye J Chen K Wang P Shen H 《Arthritis research & therapy》2011,13(1):R29-15
Introduction
Ankylosing spondylitis (AS) is a chronic autoimmune disease, and the precise pathogenesis is largely unknown at present. Bone marrow-derived mesenchymal stem cells (BMSCs) with immunosuppressive and anti-inflammatory potential and Th17/Treg cells with a reciprocal relationship regulated by BMSCs have been reported to be involved in some autoimmune disorders. Here we studied the biological and immunological characteristics of BMSCs, the frequency and phenotype of CCR4+CCR6+ Th/Treg cells and their interaction in vitro in AS.Methods
The biological and immunomodulation characteristics of BMSCs were examined by induced multiple-differentiation and two-way mixed peripheral blood mononuclear cell (PBMC) reactions or after stimulation with phytohemagglutinin, respectively. The interactions of BMSCs and PBMCs were detected with a direct-contact co-culturing system. CCR4+CCR6+ Th/Treg cells and surface markers of BMSCs were assayed using flow cytometry.Results
The AS-BMSCs at active stage showed normal proliferation, cell viability, surface markers and multiple differentiation characteristics, but significantly reduced immunomodulation potential (decreased 68 ± 14%); the frequencies of Treg and Fox-P3+ cells in AS-PBMCs decreased, while CCR4+CCR6+ Th cells increased, compared with healthy donors. Moreover, the AS-BMSCs induced imbalance in the ratio of CCR4+CCR6+ Th/Treg cells by reducing Treg/PBMCs and increasing CCR4+CCR6+ Th/PBMCs, and also reduced Fox-P3+ cells when co-cultured with PBMCs. Correlation analysis showed that the immunomodulation potential of BMSCs has significant negative correlations with the ratio of CCR4+CCR6+ Th to Treg cells in peripheral blood.Conclusions
The immunomodulation potential of BMSCs is reduced and the ratio of CCR4+CCR6+ Th/Treg cells is imbalanced in AS. The BMSCs with reduced immunomodulation potential may play a novel role in AS pathogenesis by inducing CCR4+CCR6+ Th/Treg cell imbalance. 相似文献18.
Jiao Li Shu‐Hong Li Jun Dong Faisal J. Alibhai Chongyu Zhang Zheng‐Bo Shao Hui‐Fang Song Sheng He Wen‐Juan Yin Jun Wu Richard D. Weisel Shi‐Ming Liu Ren‐Ke Li 《Aging cell》2019,18(6)
Reduced quantity and quality of stem cells in aged individuals hinders cardiac repair and regeneration after injury. We used young bone marrow (BM) stem cell antigen 1 (Sca‐1) cells to reconstitute aged BM and rejuvenate the aged heart, and examined the underlying molecular mechanisms. BM Sca‐1+ or Sca‐1? cells from young (2–3 months) or aged (18–19 months) GFP transgenic mice were transplanted into lethally irradiated aged mice to generate 4 groups of chimeras: young Sca‐1+, young Sca‐1?, old Sca‐1+, and old Sca‐1?. Four months later, expression of rejuvenation‐related genes (Bmi1, Cbx8, PNUTS, Sirt1, Sirt2, Sirt6) and proteins (CDK2, CDK4) was increased along with telomerase activity and telomerase‐related protein (DNA‐PKcs, TRF‐2) expression, whereas expression of senescence‐related genes (p16INK4a, P19ARF, p27Kip1) and proteins (p16INK4a, p27Kip1) was decreased in Sca‐1+ chimeric hearts, especially in the young group. Host cardiac endothelial cells (GFP?CD31+) but not cardiomyocytes were the primary cell type rejuvenated by young Sca‐1+ cells as shown by improved proliferation, migration, and tubular formation abilities. C‐X‐C chemokine CXCL12 was the factor most highly expressed in homed donor BM (GFP+) cells isolated from young Sca‐1+ chimeric hearts. Protein expression of Cxcr4, phospho‐Akt, and phospho‐FoxO3a in endothelial cells derived from the aged chimeric heart was increased, especially in the young Sca‐1+ group. Reconstitution of aged BM with young Sca‐1+ cells resulted in effective homing of functional stem cells in the aged heart. These young, regenerative stem cells promoted aged heart rejuvenation through activation of the Cxcl12/Cxcr4 pathway of cardiac endothelial cells. 相似文献
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Joel Gatlin David J. Unett Michael R. Lerner J. Victor Garcia 《Pigment cell & melanoma research》2001,14(4):275-282
Xenopus laevis dermal melanophores provide an excellent model system for the investigation of complex cellular processes. Specifically, the expression of exogenous genes in Xenopus melanophores is the basis of recombinant bioassays for the study of receptor–ligand interactions. However, due to their slow rate of cell division and to the relatively low efficiency of current transfection protocols, long‐term expression of exogenous genes and the generation of stable melanophore cell lines remains problematic. In this report we demonstrate the efficient, long‐term expression of two exogenous proteins, the enhanced green fluorescent protein (EGFP) and the human CD4 (hCD4) cell surface receptor, following stable introduction into Xenopus melanophores via an HIV‐1 based vector. Transduction of melanophores with the EGFP expression vector resulted in up to 80% EGFP+ cells. After 1 year in continuous culture in the absence of antibiotic selection, more than 60% of the cells remained EGFP+. Furthermore, we demonstrate the expression of hCD4 in melanophores for over 9 months in continuous culture in the absence of antibiotic selection. Our results indicate that lentivirus vectors provide an efficient means of introducing genetic information into Xenopus melanophores, resulting in sustained levels of gene expression. The significance of this gene transfer system for the study of cellular signal transduction pathways is discussed. 相似文献