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Sample records for autologous antravesical macrophage

  1. The application of adjuvant autologous antravesical macrophage cell therapy vs. BCG in non-muscle invasive bladder cancer: a multicenter, randomized trial

    Directory of Open Access Journals (Sweden)

    Kiss Tamas

    2010-06-01

    Full Text Available Abstract Introduction While adjuvant immunotherapy with Bacille Calmette Guérin (BCG is effective in non-muscle-invasive bladder cancer (BC, adverse events (AEs are considerable. Monocyte-derived activated killer cells (MAK are discussed as essential in antitumoural immunoresponse, but their application may imply risks. The present trial compared autologous intravesical macrophage cell therapy (BEXIDEM® to BCG in patients after transurethral resection (TURB of BC. Materials and methods This open-label trial included 137 eligible patients with TaG1-3, T1G1-2 plurifocal or unifocal tumours and ≥ 2 occurrences within 24 months and was conducted from June 2004 to March 2007. Median follow-up for patients without recurrence was 12 months. Patients were randomized to BCG or mononuclear cells collected by apheresis after ex vivo cell processing and activation (BEXIDEM. Either arm treatment consisted of 6 weekly instillations and 2 cycles of 3 weekly instillations at months 3 and 6. Toxicity profile (primary endpoint and prophylactic effects (secondary endpoint were assessed. Results Patient characteristics were evenly distributed. Of 73 treated with BCG and 64 with BEXIDEM, 85% vs. 45% experienced AEs and 26% vs. 14% serious AEs (SAE, respectively (p Discussion This initial report of autologous intravesical macrophage cell therapy in BC demonstrates BEXIDEM treatment to be safe. Recurrence rates were significantly lower with BCG however. As the efficacy of BEXIDEM remains uncertain, further data, e.g. marker lesions studies, are warranted. Trial registration The trial has been registered in the ISRCTN registry http://isrctn.org under the registration number ISRCTN35881130.

  2. Development of an Autologous Macrophage-based Adoptive Gene Transfer Strategy to Treat Posttraumatic Osteoarthritis (PTOA) and Osteoarithritis (OA)

    Science.gov (United States)

    2016-05-01

    including physical therapy , lifestyle changes, orthopedic bracing, and medications. Medications can help reduce inflammation in the joint to reduce pain... rheumatoid arthritis and other inflammatory-related bone diseases. 22 If there is nothing significant to report during this reporting period, state...feasibility of and efficacy for an innovative autologous macrophage- based anti-catabolic and pro-chondrogenic combination adoptive gene therapy for

  3. Comparative phenotypic and functional analyses of the effects of autologous plasma and recombinant human macrophage-colony stimulating factor (M-CSF) on porcine monocyte to macrophage differentiation.

    Science.gov (United States)

    Franzoni, Giulia; Bonelli, Piero; Graham, Simon Paul; Anfossi, Antonio Giovanni; Dei Giudici, Silvia; Pilo, Giovannantonio; Pittau, Marco; Nicolussi, Paola; Oggiano, Annalisa

    2017-05-01

    Porcine monocyte-derived macrophages (moMΦ) have been employed as a model cell in numerous studies of the porcine immune system. However, the lack of a standardized method for moMΦ differentiation hampers the comparison of results coming from the use of different laboratory protocols. In this study we compared the use of varying concentrations of autologous plasma (10, 20 and 30% v/v) or recombinant human macrophage-colony stimulating factor (hM-CSF; 50, 100, and 200ng/ml) to differentiate porcine monocytes into macrophages. Changes in cell morphology and surface marker expression were assessed by confocal microscopy and flow cytometry. Macrophage differentiation was evaluated by analysing TNF-α response to LPS stimulation and determining cytokine secretion patterns under both basal conditions and after classical and alternative activation. The effects of the differentiation methods on metabolic activity and susceptibility to infection with the myelotropic African swine fever virus (ASFV) were also evaluated. Monocytes cultured using the different culture conditions tested augmented in dimension and cellular complexity, but increasing porcine plasma concentrations resulted in a dose dependent enhancement in granularity and a marked pleomorphism. As expected, CD163, MHC class II DR and CD203a expression were up-regulated in both hM-CSF (M-CSF-moMΦ) and autologous plasma cultured macrophages (AP-moMΦ), although a lower percentage of CD163 + cells were found following differentiation with high percentages of porcine plasma. We observed enhanced number of viable cells using high concentration of hM-CSF compared to porcine plasma, suggesting a proliferative effect. Irrespective of differentiation conditions, monocyte differentiation into macrophages resulted in an increased susceptibility to ASFV and yielded larger amounts of LPS-induced TNF-α. AP-moMΦ showed a higher basal release of IL-1RA compared to those cultured with hM-CSF and displayed a reduced ability

  4. GM-CSF increases the ability of cultured macrophages to support autologous CD4+ T-cell proliferation in response to Dermatophagoides pteronyssinus and PPD antigen.

    Science.gov (United States)

    Caulfield, J J; Hawrylowicz, C M; Kemeny, D M; Lee, T H

    1997-01-01

    Previous studies have demonstrated an infiltration of monocytes and increased levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in the asthmatic lung. To study the possible effects of this cytokine upon the differentiation and function of these newly recruited monocytes, we have developed a model in which monocytes isolated from human peripheral blood were differentiated into macrophages in serum in the presence or absence of GM-CSF. After 7 days, the macrophages increased in size and granularity, had increased phagocytic activity, and expressed various adhesion molecules, CD14 and major histocompatibility complex (MHC) class II. The effects of GM-CSF on antigen presentation by cultured macrophages on the antigen-specific proliferative response of CD4+ T cells to Dermatophagoides pteronyssinus or purified protein derivative of tuberculin and the mitogen phytohaemagglutinin was determined. CD4+ T-cell proliferation was reduced when either antigen was presented by macrophages cultured in serum alone, compared with the values obtained with freshly isolated monocytes. However, CD4+ cell proliferation was comparable to that observed with monocytes when antigen was presented by macrophages which had been pre-cultured with 50 U/ml GM-CSF. CD4+ T-cell proliferation to phytohaemagglutinin was similar when all three populations were used as accessory cells. High numbers of macrophages partially suppressed CD4+ T-cell proliferation in response to antigen presented by monocytes, but there was no significant difference between macrophages cultured in the presence or absence of GM-CSF. This data suggests that GM-CSF directs monocyte differentiation into macrophages with an antigen-presenting, rather than a suppressive, phenotype. Elevated levels of GM-CSF in the asthmatic lung may therefore maintain recently recruited monocytes in an inflammatory and T-cell activating state. Images Figure 2 Figure 3 PMID:9370934

  5. Rebooting autoimmunity with autologous HSCT.

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    Snowden, John A

    2016-01-07

    Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used for severe autoimmune and inflammatory diseases, but the mechanisms involved have yet to be elucidated. In this issue of Blood, Delemarre et al report their findings in both animal and human models which provide insights into restoration of functionality and diversity within the regulatory T-cell (Treg) compartment following HSCT.

  6. Autologous Fat Injection for Augmented Mammoplasty

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    Yoon, Eul Sik; Seo, Bo Kyoung; Yi, Ann; Cho, Kyu Ran [Korea University Ansan Hospital, Ansan (Korea, Republic of)

    2008-12-15

    Autologous fat injection is one of the methods utilized for augmented mammoplasty methods. In this surgical procedure, the fat for transfer is obtained from the donor site of the patient's own body by liposuction and the fat is then injected into the breast. We report here cases of three patients who underwent autologous fat injection. Two of the patients had palpable masses that were present after surgery. The serial imaging findings and surgical method of autologous fat transfer are demonstrated

  7. Autopoiesis: Autology, Autotranscendence and Autonomy

    DEFF Research Database (Denmark)

    , to the prospects of imagination, not least because imagination is driven by such paradoxes. The depth of the imagination is all surface, and all of its surfaces are deep structures. Schiltz’s exploration of autology grows out of one of a number (a growing number) of programmes that deal seriously with the idea......¿ning) problem of modernity. Castoriadis suggests a mutual and complementary relation between subjective and collective autonomy. Bouchet’s interpretation of this is very  radical and in certain respects quite startling. He considers how in modernity emerge spontaneous social orders (like markets or publics...

  8. Screening for autologous blood transfusions

    DEFF Research Database (Denmark)

    Mørkeberg, J; Belhage, B; Ashenden, M

    2009-01-01

    The ratio between the amount of hemoglobin in the mature erythrocyte population and the reticulocytes (RBCHb:RetHb ratio) has previously been suggested as a marker to screen for EPO-abuse. We speculated that the reinfusion of blood would lead to a marked increase in this ratio, making it a valuable...... parameter in the screening for autologous blood doping. Three bags of blood (approximately 201+/-11 g of Hb) were withdrawn from 16 males and stored at either -80 degrees C (-80 T, n=8) or +4 degrees C (+4 T, n=8) and reinfused 10 weeks or 4 weeks later, respectively. Seven subjects served as controls...... week wash-out period were identified as 'suspicious', and 18.8% (-80 T) and 4.3% (+4 T) as 'positive'. In total, 7 out of 16 (43.8%) subjects had at least one sample exceeding 182.9. Compared to the currently used indirect parameters, the RBCHb:RetHb ratio is the best indicator of autologous blood...

  9. Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults

    Energy Technology Data Exchange (ETDEWEB)

    Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.

    1987-01-01

    Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

  10. Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

    DEFF Research Database (Denmark)

    Kemp, M; Hey, A S; Bendtzen, K

    1994-01-01

    resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...

  11. Intraurethral Injection of Autologous Minced Skeletal Muscle

    DEFF Research Database (Denmark)

    Gräs, Søren; Klarskov, Niels; Lose, Gunnar

    2014-01-01

    PURPOSE: Intraurethral injection of in vitro expanded autologous skeletal muscle derived cells is a new regenerative therapy for stress urinary incontinence. We examined the efficacy and safety of a simpler alternative strategy using freshly harvested, minced autologous skeletal muscle tissue...... noted. CONCLUSIONS: Intraurethral injection of minced autologous muscle tissue is a simple surgical procedure that appears safe and moderately effective in women with uncomplicated stress urinary incontinence. It compares well to a more complicated regenerative strategy using in vitro expanded muscle...... with its inherent content of regenerative cells. MATERIALS AND METHODS: A total of 20 and 15 women with uncomplicated and complicated stress urinary incontinence, respectively, received intraurethral injections of minced autologous skeletal muscle tissue and were followed for 1 year. Efficacy was assessed...

  12. Hemifacial atrophy treated with autologous fat transplantation

    Directory of Open Access Journals (Sweden)

    Gandhi Vijay

    2005-01-01

    Full Text Available A 23-year-old male developed right hemifacial atrophy following marphea profunda. Facial asymmetry due to residual atrophy was treated with autologous fat harvested from buttocks with marked cosmetic improvement.

  13. Autologous fat transplantation for labia majora reconstruction.

    Science.gov (United States)

    Vogt, P M; Herold, C; Rennekampff, H O

    2011-10-01

    A case of autologous fat transplantation for labia majora augmentation after ablative surgery is presented. The patient reported pain and deformity of the left labium majus after resection for Bowen's disease. The symptoms had not been solved by classic plastic surgical reconstructions including a pudendal thigh fasciocutaneous flap. Use of autologous fat transplantation facilitated an improved aesthetic result while preserving residual sensation to the external genitalia and improving symptoms of mucosal exposure and dryness.

  14. Macrophages and bone inflammation

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    Qiaoli Gu

    2017-07-01

    Full Text Available Bone metabolism is tightly regulated by the immune system. Accelerated bone destruction is observed in many bone diseases, such as rheumatoid arthritis, fracture, and particle-induced osteolysis. These pathological conditions are associated with inflammatory responses, suggesting the contribution of inflammation to bone destruction. Macrophages are heterogeneous immune cells and are polarized into the proinflammatory M1 and antiinflammatory M2 phenotypes in different microenvironments. The cytokines produced by macrophages depend on the macrophage activation and polarization. Macrophages and macrophage-derived cytokines are important to bone loss in inflammatory bone disease. Recent studies have shown that macrophages can be detected in bone tissue and interact with bone cells. The interplay between macrophages and bone cells is critical to bone formation and repair. In this article, we focus on the role of macrophages in inflammatory bone diseases, as well as discuss the latest studies about macrophages and bone formation, which will provide new insights into the therapeutic strategy for bone disease.

  15. [Autologous fat grafting and rhinoplasty].

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    Nguyen, P S; Baptista, C; Casanova, D; Bardot, J; Magalon, G

    2014-12-01

    Revision rhinoplasty can be very challenging especially in cases of thin skin. Autologous fat graft is utilized in numerous applications in plastic surgery; however, its use relative to the nasal region remains uncommon. Adipose tissue, by virtue of its volumetric qualities and its action on skin trophicity, can be considered to be a gold standard implant. From 2006 until 2012, we have treated patients by lipofilling in order to correct sequelae of rhinoplasty. The mean quantity of adipose tissue injected was 2.1cm(3) depending on the importance of the deformity and the area of injection: irregularity of the nasal dorsum, visible lateral osteotomies, saddle nose. Following the course of our practice, we conceived micro-cannulas that allow a much greater accuracy in the placement of the graft and enable to perform interventions under local anesthesia. These non-traumatic micro-cannulas do not cause post-operative ecchymosis and swelling which shorten the recovery time for the patient. On patients who have undergone multiple operations, lipofilling can be a simple and reliable alternative to correct imperfections that may take place after a rhinoplasty. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  16. Transabdominal sacrocolpopexy with autologous rectus fascia graft.

    Science.gov (United States)

    Abraham, Nitya; Quirouet, Adrienne; Goldman, Howard B

    2016-08-01

    Extrusion and infection are potential postoperative complications when using synthetic mesh for abdominal sacrocolpopexy. Long-term follow-up in the Colpopexy and Urinary Reduction Efforts (CARE) trial revealed an estimated 9.9 % risk of mesh extrusion. There are 26 reports of spondylodiscitis after sacrocolpopexy with synthetic mesh. These surgical risks may be decreased by using autologous fascia. To date, there have been no reports of extrusion or spondylodiscitis after using autologous fascia for sacrocolpopexy. This video demonstrates transabdominal sacrocolpopexy with an autologous rectus fascia graft. A 76-year-old woman with symptomatic stage 3 prolapse also had a history of diverticulitis and sigmoid abscess requiring sigmoid colectomy with end colostomy and incidental left ureteral transection with subsequent left nephrostomy tube placement. She presented for colostomy reversal, ureteral reimplantation, and prolapse repair. Given the need for concomitant colon and ureteral reconstruction, the risk of infection was potentially higher if synthetic mesh were used. The patient therefore underwent transabdominal sacrocolpopexy with autologous rectus fascia graft. At 4 months' follow-up the patient reported resolution of her symptoms and on examination she had no pelvic organ prolapse. Transabdominal sacrocolpopexy using autologous rectus fascia graft is a feasible option, especially in cases in which infection and synthetic mesh extrusion risks are potentially higher.

  17. Postoperative Autologous Reinfusion in Total Knee Replacement

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    A. Crescibene

    2015-01-01

    Full Text Available Surgeries for total knee replacement (TKR are increasing and in this context there is a need to develop new protocols for management and use of blood transfusion therapy. Autologous blood reduces the need for allogeneic blood transfusion and the aim of the present study was to verify the safety and the clinical efficacy. An observational retrospective study has been conducted on 124 patients, undergoing cemented total knee prosthesis replacement. Observed population was stratified into two groups: the first group received reinfusion of autologous blood collected in the postoperative surgery and the second group did not receive autologous blood reinfusion. Analysis of data shows that patients undergoing autologous blood reinfusion received less homologous blood bags (10.6% versus 30%; p=0.08 and reduced days of hospitalization (7.88 ± 0.7 days versus 8.96 ± 2.47 days for the control group; p=0.03. Microbiological tests were negative in all postoperatively salvaged and reinfused units. Our results emphasize the effectiveness of this procedure and have the characteristics of simplicity, low cost (€97.53 versus €103.79; p<0.01, and easy reproducibility. Use of autologous drainage system postoperatively is a procedure that allows reducing transfusion of homologous blood bags in patients undergoing TKR.

  18. Sites of Autologous Bone Grafts in Orthopaedic Traumatology ...

    African Journals Online (AJOL)

    Background: The use of autologous bone graft in orthopaedic traumatology is not uncommon. But little work, from West African subregion, has been devoted to sites used as sources of autologous bone grafts. Objective: The purpose of this study was to evaluate the evolution of these different sampling sites of autologous ...

  19. Autologous blood transfusion - a review | Charles | South African ...

    African Journals Online (AJOL)

    The discovery of HIV and other transfusion-transmissible infections has increased the demand for alternatives to allogeneic blood transfusion. One such alternative is autologous transfusion. This review presents an analysis of autologous transfusion. We conclude that autologous transfusion should form part of a strategy to ...

  20. Autologous fibrin adhesive in experimental tubal anastomosis.

    Science.gov (United States)

    Rajaram, S; Rusia, U; Agarwal, S; Agarwal, N

    1996-01-01

    To evaluate autologous fibrin in rabbit oviduct anastomosis versus 7-0 vikryl, a conventional suture material used in tubal anastomosis. Thrombin was added to the autologous fibrinogen at the site of anastomosis to obtain a tissue adhesive. The anastomotic time, pregnancy rate, and litter size were evaluated. Three months later, a relaparotomy was done to evaluate patency and degree of adhesions, and a tubal biopsy was taken from the site of anastomosis. Analysis of results showed a statistically significant (P < .001) shortened anastomotic time and superior histopathological union in the tissue adhesive group. Patency rate, pregnancy rate, and degree of adhesions were comparable in both groups.

  1. The elusive antifibrotic macrophage

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    Adhyatmika eAdhyatmika

    2015-11-01

    Full Text Available Fibrotic diseases, especially of the liver, the cardiovascular system, the kidneys, and the lungs account for approximately 45% of deaths in Western societies. Fibrosis is a serious complication associated with aging and/or chronic inflammation or injury and cannot be treated effectively yet. It is characterized by excessive deposition of extracellular matrix (ECM proteins by myofibroblasts and impaired degradation by macrophages. This ultimately destroys the normal structure of an organ, which leads to loss of function. Most efforts to develop drugs have focused on inhibiting ECM production by myofibroblasts and have not yielded many effective drugs yet. Another option is to stimulate the cells that are responsible for degradation and uptake of excess ECM, i.e. antifibrotic macrophages. However, macrophages are plastic cells that have many faces in fibrosis, including profibrotic behaviour stimulating ECM production. This can be dependent on their origin, as the different organs have tissue-resident macrophages with different origins and a various influx of incoming monocytes in steady-state conditions and during fibrosis. To be able to pharmacologically stimulate the right kind of behaviour in fibrosis, a thorough characterization of antifibrotic macrophages is necessary, as well as an understanding of the signals they need to degrade ECM. In this review we will summarize the current state of the art regarding the antifibrotic macrophage phenotype and the signals that stimulate its behaviour.

  2. Cord Blood Banking Standards: Autologous Versus Altruistic

    Science.gov (United States)

    Armitage, Sue

    2016-01-01

    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as “biological insurance” should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485

  3. Cord Blood Banking Standards: Autologous Versus Altruistic.

    Science.gov (United States)

    Armitage, Sue

    2015-01-01

    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards.

  4. Predonated autologous blood transfusion in elective orthopaedic ...

    African Journals Online (AJOL)

    Background: The use of homologous blood carries significant risk of viral infections and immune-mediated reactions. Preoperative autologous blood donation is an attractive alternative to homologous transfusion and has become common in elective orthopaedic surgery. Objective: To present our experience with the use of ...

  5. Autologous Fat Grafting for Whole Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Benjamin H. L. Howes, MBBS

    2014-03-01

    Full Text Available Summary: This is the first reported case of a patient who had a single-stage large-volume breast reconstruction with autologous fat grafting, following rotation flap approach (RoFA mastectomy. The purpose of this case study was to evaluate the viability of reconstruction of the breast by autologous fat grafting alone, in the context of RoFA mastectomy. The hypothesis was that there would be minimal interval loss of autologous fat on the whole breast reconstruction side. Right RoFA mastectomy was used for resection of an invasive primary breast cancer and resulted in the right breast skin envelope. Eleven months later, the patient underwent grafting of 400 ml of autologous fat into the skin envelope and underlying pectoralis major muscle. Outcome was assessed by using a validated 3D laser scan technique for quantitative breast volume measurement. Other outcome measures included the BREAST-Q questionnaire and 2D clinical photography. At 12-month follow-up, the patient was observed to have maintenance of volume of the reconstructed breast. Her BREAST-Q scores were markedly improved compared with before fat grafting, and there was observable improvement in shape, contour, and symmetry on 2D clinical photography. The 2 new techniques, RoFA mastectomy and large-volume single-stage autologous fat grafting, were used in combination to achieve a satisfactory postmastectomy breast reconstruction. Novel tools for measurement of outcome were the 3D whole-body laser scanner and BREAST-Q questionnaire. This case demonstrates the potential for the use of fat grafting for reconstruction. Outcomes in a larger patient populations are needed to confirm these findings.

  6. Autologous tumor vaccine lowering postsurgical recurrent rate of hepatocellular carcinoma.

    Science.gov (United States)

    Peng, Baogang; Liang, Lijian; Chen, Zubing; He, Qiang; Kuang, Ming; Zhou, Fan; Lu, Mingde; Huang, Jiefu

    2006-01-01

    A tumor vaccine consisting of formalin-fixed hepatocellular carcinoma (HCC) tissue fragments, biodegradable sustained-releasers of granulocyte-macrophage-colony stimulating factor (GM-CSF) and interleukin-2 (IL-2), and an adjuvant was developed. The aim of this study was to evaluate the effects of autologous tumor vaccine for protective immunity against HCC. C57BL/6J mice were immunized intradermally with the Hepa1-6 tumor vaccine on day 0 and 7, followed by intrahepatic challenge with live Hepa1-6 cells. On day 21, the tumor volumes were measured and the effect of tumor vaccine was evaluated. Lymphocytes from the immunized mice were cultured and the specific cytotoxicity against Hepa1-6 was accessed. Then from March 1999 to June 2003, 67 patients with HCC undergoing curative resection were randomly divided into a tumor vaccine group (n = 32) and a control group (n = 35). Patients in the tumor vaccine group received 3 vaccinations at a 2-week interval and the control group only adjuvant treatment for symptoms. A delayed-type-hypersensitivity test was performed before and after vaccination. Primary endpoint was time to first recurrence and recurrent rates were analyzed. The tumor vaccine protected 87% of syngeneic mice from Hepa1-6 cells inoculation. In an in vitro experiment, splenocytes from the vaccinated mice exhibited a 56% lytic activity against the Hepa1-6 cells at an effector/target (E/T) ratio of 5, whereas they did not exhibit such activity against other tumor cells. The cytotoxic activity was inhibited by the treatment with anti-CD3, anti-CD8, and anti-MHC-class II monoclonal antibodies but not with anti-CD4 and anti-MHC-class I antibodies. In clinical trial, thirty-two patients had completed the tumor vaccine procedure and no essential adverse effect occurred. The follow-up averaged 33.6 months (range from 15 to 54 months). The recurrent rate was significantly better in the tumor vaccine group (1 year, 12.6%; 2 years, 35.9%; 3 years, 54%) than in the

  7. [Macrophages in asthma].

    Science.gov (United States)

    Medina Avalos, M A; Orea Solano, M

    1997-01-01

    Every time they exist more demonstrations of the paper than performs the line monocytes-macrophage in the patogenesis of the bronchial asthma. The mononuclear phagocytes cells, as the alveolar macrophages, also they can be activated during allergic methods. The monocytes macrophages are possible efficient inductors of the inflammation; this due to the fact that they can secrete inflammatory mediators, between those which are counted the pre-forming granules of peptides, metabolites of oxidation activation, activator of platelets activator and metabolites of the arachidonic acid. The identification of IL-1 in the liquidate of the bronchial ablution of sick asthmatic, as well as the identification of IL-1 in the I bronchioalveolar washing of places of allergens cutaneous prick, supports the activation concept mononuclear of phagocytic cells in allergic sufferings.

  8. Autologous Fat Grafting Improves Facial Nerve Function

    Directory of Open Access Journals (Sweden)

    Marco Klinger

    2015-01-01

    Full Text Available We describe the case of a 45-year-old male patient who presented a retractile and painful scar in the nasolabial fold due to trauma which determined partial motor impairment of the mouth movements. We subsequently treated him with autologous fat grafting according to Coleman’s technique. Clinical assessments were performed at 5 and 14 days and 1, 3, and 6 months after surgical procedure and we observed a progressive release of scar retraction together with an important improvement of pain symptoms. A second procedure was performed 6 months after the previous one. We observed total restoration of mimic movements within one-year follow-up. The case described confirms autologous fat grafting regenerative effect on scar tissue enlightening a possible therapeutic effect on peripheral nerve activity, hypothesizing that its entrapment into scar tissue can determine a partial loss of function.

  9. Modulation of allogeneic stimulation in man. I. Characterization of an in vitro induced suppressor macrophage population

    International Nuclear Information System (INIS)

    Stux, S.V.; Dubey, D.P.; Yunis, E.J.

    1981-01-01

    Cultured human peripheral blood mononuclear cells suppressed the allogeneic response of fresh autologous lymphocytes. This suppressor activity developed gradually over a period of one week. The cells primarily responsible for this effect were enriched by Ficoll density gradient centrifugation. It was found that the suppressor cell is a large, low density nylon wool adherent, radioresistant, phagocytic, and nonspecific esterase positive mononuclear cell. Moreover, these cells did not form E rosettes and were Fc positive. Electron microscopy confirmed that suppressor cells were macrophage like. Suppressor activity was not due to cytotoxicity, crowding, or steric hinderance by the cultured cells. The suppressor macrophage population did not appear to inhibit the allogeneic response via prostaglandin or arginase release, or interfere with the tritiated thymidine uptake by release of endogenous thymidine. The above system is viewed as an in vitro model of immune regulation by suppressor macrophages, in the context of allogeneic response

  10. Tumescent mastectomy technique in autologous breast reconstruction.

    Science.gov (United States)

    Vargas, Christina R; Koolen, Pieter G L; Ho, Olivia A; Ricci, Joseph A; Tobias, Adam M; Lin, Samuel J; Lee, Bernard T

    2015-10-01

    Use of the tumescent mastectomy technique has been reported to facilitate development of a hydrodissection plane, reduce blood loss, and provide adjunct analgesia. Previous studies suggest that tumescent dissection may contribute to adverse outcomes after immediate implant reconstruction; however, its effect on autologous microsurgical reconstruction has not been established. A retrospective review was conducted of all immediate microsurgical breast reconstruction procedures at a single academic center between January 2004 and December 2013. Records were queried for age, body mass index, mastectomy weight, diabetes, hypertension, smoking, preoperative radiation, reconstruction flap type, and autologous flap weight. Outcomes of interest were mastectomy skin necrosis, complete and partial flap loss, return to the operating room, breast hematoma, seroma, and infection. There were 730 immediate autologous breast reconstructions performed during the study period; 46% with the tumescent dissection technique. Groups were similar with respect to baseline patient and procedural characteristics. Univariate analysis revealed no significant difference in the incidence of mastectomy skin necrosis, complete or partial flap loss, return to the operating room, operative time, estimated blood loss, recurrence, breast hematoma, seroma, or infection in patients undergoing tumescent mastectomy. Multivariate analysis also demonstrated no significant association between the use of tumescent technique and postoperative breast mastectomy skin necrosis (P = 0.980), hematoma (P = 0.759), or seroma (P = 0.340). Use of the tumescent dissection technique during mastectomy is not significantly associated with adverse outcomes after microsurgical breast reconstruction. Despite concern for its impact on implant reconstruction, our findings suggest that this method can be used safely preceding autologous procedures. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Autologous Stem Cell Transplant for AL Amyloidosis

    OpenAIRE

    Roy, Vivek

    2012-01-01

    AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors) has increased treatment options. Autologous stem cell transplant (ASCT) has been used in the treatment of ...

  12. Wormhole Travel for Macrophages.

    Science.gov (United States)

    Okabe, Yasutaka; Medzhitov, Ruslan

    2016-04-21

    Leukocyte recruitment is generally achieved by rapid migration of inflammatory cells out of circulation, through modified blood vessels, and into affected tissues. Now, Wang and Kubes show that macrophages can be rapidly recruited from body cavities to the liver, via a non-vascular route, where they help to coordinate tissue repair. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The effects of exogenous fatty acids and niacin on human monocyte-macrophage plasticity.

    Science.gov (United States)

    Montserrat-de la Paz, Sergio; Rodriguez, Dolores; Cardelo, Magdalena P; Naranjo, Maria C; Bermudez, Beatriz; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

    2017-08-01

    Macrophage plasticity allows adapting to different environments, having a dual activity in inflammatory-related diseases. Our hypothesis is that the type of dietary fatty acids into human postprandial triglyceride-rich lipoproteins (TRLs), alone or in combination with niacin (vitamin B3), could modulate the plasticity of monocytes-macrophages. We isolated TRLs at the postprandial peak from blood samples of healthy volunteers after the ingestion of a meal rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs) or MUFAs plus omega-3 long-chain polyunsaturated fatty acids (LCPUFAs). Autologous monocytes isolated at fasting were first induced to differentiate into naïve macrophages. We observed that postprandial TRL-MUFAs, particularly in combination with niacin, enhance competence to monocytes to differentiate and polarise into M2 macrophages. Postprandial TRL-SFAs made polarised macrophages prone to an M1 phenotype. In contrast to dietary SFAs, dietary MUFAs in the meals plus immediate-release niacin primed circulating monocytes for a reduced postprandial pro-inflammatory profile. Our study underlines a role of postprandial TRLs as a metabolic entity in regulating the plasticity of the monocyte-macrophage lineage and also brings an understanding of the mechanisms by which dietary fatty acids are environmental factors fostering the innate immune responsiveness in humans. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Autologous growth factor injections in chronic tendinopathy.

    Science.gov (United States)

    Sandrey, Michelle A

    2014-01-01

    de Vos RJ, van Veldhoven PLJ, Moen MH, Weir A, Tol JL. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull. 2010;95:63-77. The authors of this systematic review evaluated the literature to critically consider the effects of growth factors delivered through autologous whole-blood and platelet-rich-plasma (PRP) injections in managing wrist-flexor and -extensor tendinopathies, plantar fasciopathy, and patellar tendinopathy. The primary question was, according to the published literature, is there sufficient evidence to support the use of growth factors delivered through autologous whole-blood and PRP injections for chronic tendinopathy? The authors performed a comprehensive, systematic literature search in October 2009 using PubMed, MEDLINE, EMBASE, CINAHL, and the Cochrane library without time limits. The following key words were used in different combinations: tendinopathy, tendinosis, tendinitis, tendons, tennis elbow, plantar fasciitis, platelet rich plasma, platelet transfusion, and autologous blood or injection. The search was limited to human studies in English. All bibliographies from the initial literature search were also viewed to identify additional relevant studies. Studies were eligible based on the following criteria: (1) Articles were suitable (inclusion criteria) if the participants had been clinically diagnosed as having chronic tendinopathy; (2) the design had to be a prospective clinical study, randomized controlled trial, nonrandomized clinical trial, or prospective case series; (3) a well-described intervention in the form of a growth factor injection with either PRP or autologous whole blood was used; and (4) the outcome was reported in terms of pain or function (or both). All titles and abstracts were assessed by 2 researchers, and all relevant articles were obtained. Two researchers independently read the full text of each article to determine if it met the inclusion criteria. If opinions differed on

  15. The macrophages in rheumatic diseases

    Directory of Open Access Journals (Sweden)

    Laria A

    2016-02-01

    Full Text Available Antonella Laria, Alfredomaria Lurati , Mariagrazia Marrazza , Daniela Mazzocchi, Katia Angela Re, Magda Scarpellini Rheumatology Unit, Fornaroli Hospital, Magenta, Italy Abstract: Macrophages belong to the innate immune system giving us protection against pathogens. However it is known that they are also involved in rheumatic diseases. Activated macrophages have two different phenotypes related to different stimuli: M1 (classically activated and M2 (alternatively activated. M1 macrophages release high levels of pro-inflammatory cytokines, reactive nitrogen and oxygen intermediates killing microorganisms and tumor cells; while M2 macrophages are involved in resolution of inflammation through phagocytosis of apoptotic neutrophils, reduced production of pro-inflammatory cytokines, and increased synthesis of mediators important in tissue remodeling, angiogenesis, and wound repair. The role of macrophages in the different rheumatic diseases is different according to their M1/M2 macrophages phenotype. Keywords: macrophage, rheumatic diseases

  16. Use of autologous blood in general surgery.

    Science.gov (United States)

    D'Amato, A; Ferrazza, G; Solinas, S; Pronio, A M; Montesani, C; Ribotta, G

    2000-01-01

    Autologous blood predonation is still not as widespread as it should be in general surgery practice, even if the method is well-known and has benefits established in international literature. Authors describe the impact of an autotransfusion program, in a general surgery university department, focusing on management and cost problems. A description of the efficacy of the program during a yearlong activity period is presented. An analysis has been made about the quantity of predonated blood/plasma units, the quantity actually transfused and use of homologous blood. The problems which occurred and the cost are discussed. The most used autotransfusion method was preoperative predeposit of autologous blood. The analysis of results focused on some organizational problems that need to be avoided in order to show the methods maximum benefits. In a large number of cases (some 50%) predeposit was not made because of several managing/technical problems. In another large number of cases (38%) the quantity of units predonated did not fully supply the needs and several patients received homologous products. In another number of cases predonated blood units were not used at all (61/34%). Predeposit, preoperative hemodilution and intraoperative recovery, are methods that should all be available in a general surgery department to manage in the best way the single patients blood/plasma needs, reducing post-transfusion complication. To optimize the program and minimize waste some guidelines must be established, with the aim of a rational and correct use of the procedure. Despite the value of the method, and the favor encountered by the patients, we must not forget that the use of autologous blood is not costless.

  17. Macrophages, PPARs, and Cancer

    Directory of Open Access Journals (Sweden)

    Jo A. Van Ginderachter

    2008-01-01

    Full Text Available Mononuclear phagocytes often function as control switches of the immune system, securing the balance between pro- and anti-inflammatory reactions. For this purpose and depending on the activating stimuli, these cells can develop into different subsets: proinflammatory classically activated (M1 or anti-inflammatory alternatively activated (M2 macrophages. The expression of the nuclear peroxisome proliferator-activated receptors (PPARs is regulated by M1- or M2-inducing stimuli, and these receptors are generally considered to counteract inflammatory M1 macrophages, while actively promoting M2 activation. This is of importance in a tumor context, where M1 are important initiators of inflammation-driven cancers. As a consequence, PPAR agonists are potentially usefull for inhibiting the early phases of tumorigenesis through their antagonistic effect on M1. In more established tumors, the macrophage phenotype is more diverse, making it more difficult to predict the outcome of PPAR agonism. Overall, in our view current knowledge provides a sound basis for the clinical evaluation of PPAR ligands as chemopreventive agents in chronic inflammation-associated cancer development, while cautioning against the unthoughtful application of these agents as cancer therapeutics.

  18. Cost effectiveness of autologous blood transfusion – A developing ...

    African Journals Online (AJOL)

    An autologous blood donation program was set up at National Orthopaedic Hospital, Igbobi Lagos in 1992 in response to the rising sero prevalence of HIV observed in our “relative replacement” donors. A retrospective batch analysis of patients who received autologous transfusion and those who received homologous ...

  19. Review of autologous blood transfusion at the Kenyatta National ...

    African Journals Online (AJOL)

    Autologous blood transfusion refers to transfusion of blood and/or blood components that are donated by the intended recipient (1). It is considered as one of the safest methods of blood transfusion (1,2). Different types of autologous blood include: preoperative blood deposit, preoperative haemodilution,intraope.

  20. Detection of accessory spleens with indium 111-labeled autologous platelets

    International Nuclear Information System (INIS)

    Davis, H.H. II; Varki, A.; Heaton, W.A.; Siegel, B.A.

    1980-01-01

    In two patients with recurrent immune thrombocytopenia, accessory splenic tissue was demonstrated by radionuclide imaging following administration of indium 111-labeled autologous platelets. In one of these patients, no accessory splenic tissue was seen on images obtained with technetium 99m sulfur colloid. This new technique provides a simple means for demonstrating accessory spleens and simultaneously evaluating the life-span of autologous platelets

  1. Disseminated Fusarium infection in autologous stem cell transplant recipient

    OpenAIRE

    Avelino-Silva, Vivian Iida; Ramos, Jessica Fernandes; Leal, Fabio Eudes; Testagrossa, Leonardo; Novis, Yana Sarkis

    2015-01-01

    Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusarium infection in an autologous bone marrow transplant recipient during pre-engraftment phase.

  2. Disseminated Fusarium infection in autologous stem cell transplant recipient

    Directory of Open Access Journals (Sweden)

    Vivian Iida Avelino-Silva

    2015-01-01

    Full Text Available Disseminated infection by Fusarium is a rare, frequently lethal condition in severely immunocompromised patients, including bone marrow transplant recipients. However, autologous bone marrow transplant recipients are not expected to be at high risk to develop fusariosis. We report a rare case of lethal disseminated Fusarium infection in an autologous bone marrow transplant recipient during pre-engraftment phase.

  3. Autologous Bone Grafts Use in Orthopaedic Practice in Abuja ...

    African Journals Online (AJOL)

    Background: There is widespread use of autologous bone grafts in orthopaedic practice in Nigeria but detailed indications, donor sites and complications following use have not been reported in different regions. Objective: This is to highlight the indications, sources and complications of autologous bone grafts use in Abuja, ...

  4. Inhibition of HIV-1 replication in macrophages by a heterodinucleotide of lamivudine and tenofovir.

    Science.gov (United States)

    Rossi, Luigia; Franchetti, Palmarisa; Pierigé, Francesca; Cappellacci, Loredana; Serafini, Sonja; Balestra, Emanuela; Perno, Carlo-Federico; Grifantini, Mario; Caliò, Raffaele; Magnani, Mauro

    2007-04-01

    (i) To generate a new heterodinucleotide (3TCpPMPA) comprising the drugs lamivudine and tenofovir which have been shown to act synergistically and (ii) to protect macrophages from 'de novo' HIV-1-infection through its administration. 3TCpPMPA was obtained by coupling the morpholidate derivative of tenofovir with the mono n-tri-butylammonium salt of lamivudine 5'-monophosphate. Stability and metabolism were evaluated in vitro and in vivo in mice. 3TCpPMPA was encapsulated into autologous erythrocytes by a procedure of hypotonic dialysis, isotonic resealing and reannealing. 3TCpPMPA-loaded erythrocytes were modified to increase their phagocytosis by human macrophages. Macrophages were infected by HIV-1(Ba-L) and inhibition of HIV-1 replication was assessed by HIV p24(gag) quantification. Pharmacokinetic studies in mice revealed a rapid disappearance of the heterodinucleotide from circulation (t(1/2)=15 min) without any advantage compared with the administration of single drugs. Adding free 3TCpPMPA to macrophages (18 h), a 90% inhibition of viral replication up to 35 days post-treatment was achieved, while only a 60% inhibition was obtained by the combined treatment 3TC and (R)PMPA. When 3TCpPMPA was selectively targeted to the macrophage compartment by a single addition of loaded erythrocytes, the protection of macrophages from 'de novo' infection (99% protection 3 weeks post-treatment) was nearly complete. Erythrocytes loaded with 3TCpPMPA and modified to increase their phagocytosis are able to protect macrophages from 'de novo' HIV-1 infection. 3TCpPMPA acts as an efficient antiviral pro-drug that, once inside macrophages, can be slowly converted into 3TCMP and (R)PMPA protecting these cells for a longer period of time.

  5. Macrophage immunoregulatory pathways in tuberculosis.

    Science.gov (United States)

    Rajaram, Murugesan V S; Ni, Bin; Dodd, Claire E; Schlesinger, Larry S

    2014-12-01

    Macrophages, the major host cells harboring Mycobacterium tuberculosis (M.tb), are a heterogeneous cell type depending on their tissue of origin and host they are derived from. Significant discord in macrophage responses to M.tb exists due to differences in M.tb strains and the various types of macrophages used to study tuberculosis (TB). This review will summarize current concepts regarding macrophage responses to M.tb infection, while pointing out relevant differences in experimental outcomes due to the use of divergent model systems. A brief description of the lung environment is included since there is increasing evidence that the alveolar macrophage (AM) has immunoregulatory properties that can delay optimal protective host immune responses. In this context, this review focuses on selected macrophage immunoregulatory pattern recognition receptors (PRRs), cytokines, negative regulators of inflammation, lipid mediators and microRNAs (miRNAs). Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Complications Following Autologous Latissimus Flap Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    Mufid Burgić

    2010-02-01

    Full Text Available Use of an autologous latissimus flap in breast reconstruction accounts for a supple and natural look of reconstructed breast. Most common postoperative complication, seroma, became more of a rule then an exception when it comes to postoperative evaluation of the patients who underwent this reconstructive procedure. A retrospective study analysing and evaluating different complication rates in 20 patients who underwent breast reconstruction by autologous latissimus flap, was conducted. All patients included in the study were operated at the Department of plastic surgery of Hôpital Civil in Strasbourg, France, between 1996 and 2008. The complication rates were noted as follows: seroma in 19 of our 20 patients (95%, late hypertrophic scarring in 3 patients (15%, postoperative surgical site hematoma in 3 patients (15%, and 2 patients (10% presented postoperative chronic back pain. Different options used in seroma treatment and prevention (subcutaneous-fascia anchor sutures of donor site, application of corticosteroids by injection into donor site postoperatively, passive drainage can reduce seroma formation and thus overall complication rates, leading to much faster patient’s recovery time and return to normal daily activities.

  7. Cartilage repair: Generations of autologous chondrocyte transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Marlovits, Stefan [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)]. E-mail: stefan.marlovits@meduniwien.ac.at; Zeller, Philip [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Singer, Philipp [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Resinger, Christoph [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Vecsei, Vilmos [Department of Traumatology, Center for Joint and Cartilage, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2006-01-15

    Articular cartilage in adults has a limited capacity for self-repair after a substantial injury. Surgical therapeutic efforts to treat cartilage defects have focused on delivering new cells capable of chondrogenesis into the lesions. Autologous chondrocyte transplantation (ACT) is an advanced cell-based orthobiologic technology used for the treatment of chondral defects of the knee that has been in clinical use since 1987 and has been performed on 12,000 patients internationally. With ACT, good to excellent clinical results are seen in isolated post-traumatic lesions of the knee joint in the younger patient, with the formation of hyaline or hyaline-like repair tissue. In the classic ACT technique, chondrocytes are isolated from small slices of cartilage harvested arthroscopically from a minor weight-bearing area of the injured knee. The extracellular matrix is removed by enzymatic digestion, and the cells are then expanded in monolayer culture. Once a sufficient number of cells has been obtained, the chondrocytes are implanted into the cartilage defect, using a periosteal patch over the defect as a method of cell containment. The major complications are periosteal hypertrophy, delamination of the transplant, arthrofibrosis and transplant failure. Further improvements in tissue engineering have contributed to the next generation of ACT techniques, where cells are combined with resorbable biomaterials, as in matrix-associated autologous chondrocyte transplantation (MACT). These biomaterials secure the cells in the defect area and enhance their proliferation and differentiation.

  8. Macrophages in Homeostatic Immune Function

    Directory of Open Access Journals (Sweden)

    Jonathan eJantsch

    2014-05-01

    Full Text Available Macrophages are not only involved in inflammatory and anti-infective processes, but also play an important role in maintaining tissue homeostasis. In this review, we summarize recent evidence investigating the role of macrophages in controlling angiogenesis, metabolism and salt and water balance. Particularly, we summarize the importance of macrophage tonicity enhancer binding protein (TonEBP, also termed nuclear factor of activated T-cells 5 [NFAT5] expression in the regulation of salt and water homeostasis. Further understanding of homeostatic macrophage function may lead to new therapeutic approaches to treat ischemia, hypertension and metabolic disorders.

  9. Predeposit autologous blood transfusion: Do we require to promote it?

    Directory of Open Access Journals (Sweden)

    Gurjit Singh

    2015-01-01

    Full Text Available Introduction: Safest blood a patient can receive is his own. Quest for safe blood transfusion has remained of prime concern. To meet this aspiration, various forms of autologous blood transfusions can be practiced. It is especially suitable for patients with rare blood groups and religious sects such as Jehovah′s witness autologous transfusion is extremely safe. Cross matching is not required; iso-immunization to a foreign body is excluded. Fear of transfusion transmissible disease can be ignored. Therefore, autologous blood transfusion is required to be revisited. Materials and Methods: This is a prospective study carried out at Padmashree Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune between July 2010 and May 2012. Study comprised of 100 patients divided into two groups, autologous and homologous. Benefits of autologous transfusion were studied. Results: There was no significant change in hematocrit and blood parameters after blood donation. That is mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (P < 0.001 after blood donation. Only one complication of vasovagal syncope was observed at the time of blood donation. Conclusion: Autologous blood transfusion is safe. Easy alternative to be practiced in elective surgeries, especially in patients with rare blood group or believers of Jehovah′s witness faith. It helps to reduce the shortfall in national blood inventory. Autologous blood donation should be practiced whenever possible.

  10. Biology of Bony Fish Macrophages

    Directory of Open Access Journals (Sweden)

    Jordan W. Hodgkinson

    2015-11-01

    Full Text Available Macrophages are found across all vertebrate species, reside in virtually all animal tissues, and play critical roles in host protection and homeostasis. Various mechanisms determine and regulate the highly plastic functional phenotypes of macrophages, including antimicrobial host defenses (pro-inflammatory, M1-type, and resolution and repair functions (anti-inflammatory/regulatory, M2-type. The study of inflammatory macrophages in immune defense of teleosts has garnered much attention, and antimicrobial mechanisms of these cells have been extensively studied in various fish models. Intriguingly, both similarities and differences have been documented for the regulation of lower vertebrate macrophage antimicrobial defenses, as compared to what has been described in mammals. Advances in our understanding of the teleost macrophage M2 phenotypes likewise suggest functional conservation through similar and distinct regulatory strategies, compared to their mammalian counterparts. In this review, we discuss the current understanding of the molecular mechanisms governing teleost macrophage functional heterogeneity, including monopoetic development, classical macrophage inflammatory and antimicrobial responses as well as alternative macrophage polarization towards tissues repair and resolution of inflammation.

  11. SIV Infection of Lung Macrophages.

    Directory of Open Access Journals (Sweden)

    Yue Li

    Full Text Available HIV-1 depletes CD4+ T cells in the blood, lymphatic tissues, gut and lungs. Here we investigated the relationship between depletion and infection of CD4+ T cells in the lung parenchyma. The lungs of 38 Indian rhesus macaques in early to later stages of SIVmac251 infection were examined, and the numbers of CD4+ T cells and macrophages plus the frequency of SIV RNA+ cells were quantified. We showed that SIV infected macrophages in the lung parenchyma, but only in small numbers except in the setting of interstitial inflammation where large numbers of SIV RNA+ macrophages were detected. However, even in this setting, the number of macrophages was not decreased. By contrast, there were few infected CD4+ T cells in lung parenchyma, but CD4+ T cells were nonetheless depleted by unknown mechanisms. The CD4+ T cells in lung parenchyma were depleted even though they were not productively infected, whereas SIV can infect large numbers of macrophages in the setting of interstitial inflammation without depleting them. These observations point to the need for future investigations into mechanisms of CD4+ T cell depletion at this mucosal site, and into mechanisms by which macrophage populations are maintained despite high levels of infection. The large numbers of SIV RNA+ macrophages in lungs in the setting of interstitial inflammation indicates that lung macrophages can be an important source for SIV persistent infection.

  12. Epigenetic regulation of macrophage function

    NARCIS (Netherlands)

    Hoeksema, M.A.

    2016-01-01

    Atherosclerosis is a lipid-driven chronic inflammatory disorder with a key role for macrophages in all disease stages. Macrophages are involved as scavengers of lipids, regulate inflammation, attract other immune cells and contribute to the resolution of inflammation, fibrosis and plaque stability.

  13. Autologous Stem Cell Transplant for AL Amyloidosis

    Directory of Open Access Journals (Sweden)

    Vivek Roy

    2012-01-01

    Full Text Available AL amyloidosis is caused by clonal plasma cells that produce immunoglobulin light chains which misfold and get deposited as amyloid fibrils. Therapy directed against the plasma cell clone leads to clinical benefit. Melphalan and corticosteroids have been the mainstay of treatment for a number of years and the recent availability of other effective agents (IMiDs and proteasome inhibitors has increased treatment options. Autologous stem cell transplant (ASCT has been used in the treatment of AL amyloidosis for many years. It is associated with high rates of hematologic response and improvement in organ function. However, transplant carries considerable risks. Careful patient selection is important to minimize transplant related morbidity and mortality and ensure optimal patient outcomes. As newer more affective therapies become available the role and timing of ASCT in the overall treatment strategy of AL amyloidosis will need to be continually reassessed.

  14. Surgical management and autologous intestinal reconstruction in short bowel syndrome

    NARCIS (Netherlands)

    Hommel, Matthijs J.; van Baren, Robertine; Haveman, Jan Willem

    Short bowel syndrome (SBS) is a serious condition with considerable morbidity and mortality. When treatment with parenteral nutrition fails and life-threatening complications occur, autologous intestinal reconstruction (AIR) should be considered before intestinal transplantation (ITx). Single or

  15. Autologous bone marrow mononuclear cell delivery to dilated ...

    African Journals Online (AJOL)

    Autologous bone marrow mononuclear cell delivery to dilated cardiomyopathy patients: A clinical trial. PLN Kaparthi, G Namita, LK Chelluri, VSP Rao, PK Shah, A Vasantha, SK Ratnakar, K Ravindhranath ...

  16. DMPD: Macrophage-stimulating protein and RON receptor tyrosine kinase: potentialregulators of macrophage inflammatory activities. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12472665 Macrophage-stimulating protein and RON receptor tyrosine kinase: potential...:545-53. (.png) (.svg) (.html) (.csml) Show Macrophage-stimulating protein and RON receptor tyrosine kinase:... potentialregulators of macrophage inflammatory activities. PubmedID 12472665 Title Macrophage-stimu

  17. Metabolic reprogramming in macrophage polarization

    Directory of Open Access Journals (Sweden)

    Silvia eGalván-Peña

    2014-09-01

    Full Text Available Studying the metabolism of immune cells in recent years has emphasized the tight link existing between the metabolic state and the phenotype of these cells. Macrophages in particular are a good example of this phenomenon. Whether the macrophage obtains its energy through glycolysis or through oxidative metabolism can give rise to different phenotypes. Classically activated or M1 macrophages are key players of the first line of defense against bacterial infections and are known to obtain energy through glycolysis. Alternatively activated or M2 macrophages on the other hand, are involved in tissue repair and wound healing and use oxidative metabolism to fuel their longer-term functions. Metabolic intermediates however, are not just a source of energy but can be directly implicated in a particular macrophage phenotype. In M1 macrophages, the Krebs cycle intermediate succinate regulates HIF1α, which is responsible for driving the sustained production of the pro-inflammatory cytokine IL1β. In M2 macrophages, the sedoheptulose kinase CARKL is critical for regulating the pentose phosphate pathway. The potential to target these events and impact on disease is an exciting prospect.

  18. Macrophage heterogeneity in lymphoid tissues.

    Science.gov (United States)

    den Haan, Joke M M; Martinez-Pomares, Luisa

    2013-09-01

    Macrophages in lymphoid organs exhibit a wide variety of phenotypes and functions. These cells excel in the removal of apoptotic cells that arise during the generation of immune cells and are thereby essential for the prevention of auto-immune responses. In addition to this macrophages in the secondary lymphoid organs form an important barrier for spreading of infections by phagocytosis of pathogens and the activation of both innate and adaptive immune responses. Thus, the remarkable ability of macrophages to phagocytose and handle a wide range of self and non-self material and to produce immunomediators is effectively exploited within lymphoid organs to regulate immune activation.

  19. The macrophage switch in obesity development

    Directory of Open Access Journals (Sweden)

    Angela eCastoldi

    2016-01-01

    Full Text Available Immune cell infiltration in (white adipose tissue during obesity is associated with the development of insulin resistance. In adipose tissue, the main population of leukocytes are macrophages. Macrophages can be classified into two major populations: M1, classically activated macrophages, and M2, alternatively activated macrophages, although recent studies have identified a broad range of macrophage subsets. During obesity, adipose tissue M1 macrophage numbers increase and correlate with adipose tissue inflammation and insulin resistance. Upon activation, pro-inflammatory M1 macrophages induce aerobic glycolysis. By contrast, in lean humans and mice, the number of M2 macrophages predominates. M2 macrophages secrete anti-inflammatory cytokines and utilize oxidative metabolism to maintain adipose tissue homeostasis. Here we review the immunologic and metabolic functions of adipose tissue macrophages and their different facets in obesity and the metabolic syndrome.

  20. Inflammatory effects of autologous, genetically modified autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

    Science.gov (United States)

    Pigott, J H; Ishihara, A; Wellman, M L; Russell, D S; Bertone, A L

    2013-01-01

    To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain. There were not any significant differences between autologous and genetically modified autologous MSC for synovial fluid total nucleated cell count, total protein, interleukin (IL)-6, IL-10, fetlock circumference, oedema score, pain-free range-of-motion, and soluble gene products that were detected for at least two days. Allogeneic and xenogeneic MSC produced a greater increase in peak of inflammation at 24 hours than either autologous MSC group. Genetically engineered MSC can act as vehicles to deliver gene products to the joint; further investigation into the therapeutic potential of this cell therapy is warranted. Intra-articular MSC injection resulted in a moderate acute inflammatory joint response that was greater for allogeneic and xenogeneic MSC than autologous MSC. Clinical management of this response may minimize this effect.

  1. Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

    Directory of Open Access Journals (Sweden)

    Alexander RW

    2013-04-01

    Full Text Available Robert W Alexander,1 David Harrell2 1Department of Surgery, School of Medicine and Dentistry, University of Washington, Seattle, WA, USA; 2Harvest-Terumo Inc, Plymouth, MA, USA Objectives: Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG with use of disposable, microcannula systems. Design: Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results: Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion: Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are

  2. Autologous Blood Transfusion for Postpartum Hemorrhage.

    Science.gov (United States)

    Greenawalt, Julia A; Zernell, Denise

    Postpartum hemorrhage (PPH) is a leading contributor to maternal morbidity and mortality in the United States and globally. Although the rate of PPH is generally decreasing nationally, severity of PPH appears to be increasing, potentially related to the various comorbidities associated with women of childbearing age. There is increasing evidence of risks associated with allogeneic blood transfusion, which has historically been the classic therapeutic approach for treatment to PPH. Pregnant women are particularly susceptible to the implications of sensitization to red cell antigens, a common sequela to allogenic blood transfusion. Autologous blood transfusion eliminates the potential of communicable disease transmission as well as the conceivable threat of a blood transfusion reaction. Recent technological advances allow cell salvage coupled with the use of a leukocyte filter to be used as an alternative approach for improving the outcome for women experiencing a PPH. Modest changes in standard operating procedure and continued training in use and application of cell salvaged blood may assist in minimizing negative outcomes from PPH. Salvaged blood has been demonstrated to be at least equal and often superior to banked blood. We discuss nursing implications for application of this technology for women with PPH. Continued research is warranted to evaluate the impact that application of cell salvage with filtration has on the patient experiencing a PPH.

  3. [Significance and technique of autologous chondrocyte transplantation].

    Science.gov (United States)

    Fritz, J; Gaissmaier, C; Schewe, B; Weise, K

    2005-08-01

    The bad risk for an early onset of osteoarthritis in the knee increases with the size of a cartilage defect. A collateral meniscus- or ligament-tear will enforce this hazard in addition. In order to avoid such a development, relevant full-thickness cartilage defects should be reconstructed biologically and attendant meniscus- or ligament-tears as well as varus- or valgus deformities should be treated. A number of studies, including some prospective-randomized trials, have shown that autologous chondrocyte transplantation (ACT) is the most reliable procedure for a surgical treatment of full-thickness cartilage defects larger than 4 cm (2) in adults. One disadvantage of ACT is the extensive approach to the joint and often a hypertrophy of the repair tissue. To solve these problems, some different biomaterials for a matrix-assisted ACT have been developed. The scaffold we use has a covering membrane upside and a collagen-sponge carrying the chondrocytes. By means of special surgical instruments a minimally invasive implantation is possible, reducing the side-effects of an extensive approach. Animal studies showed the regeneration of a hyaline cartilage using our described system. However, results of current clinical studies with the different scaffolds must be awaited before an universal application of matrix-assisted ACT can be recommended.

  4. Streptococcus salivarius-mediated CD8+T cell stimulation required antigen presentation by macrophages in oral squamous cell carcinoma.

    Science.gov (United States)

    Wang, Jie; Yang, Lina; Mao, Xiaohe; Li, Zaiye; Lin, Xiaoyu; Jiang, Canhua

    2018-05-15

    It has been shown that the peripheral blood mononuclear cells (PBMCs) from oral squamous cell carcinoma (OSCC) patients presented cytotoxic CD8 T cell response against Streptococcus salivarius (S. salivarius), of which the frequency was positively associated with recurrence-free survival in OSCC patients. To identify the conditions required for regulating S. salivarius-specific CD8 T cell-mediated cytotoxicity, we selectively depleted individual components of the PBMCs, and observed that the depletion of monocytes/macrophages, but not other immune cell subsets, significantly downregulated the S. salivarius-specific CD8 T cell cytotoxicity. Monocyte/macrophage alone was sufficient to reconstitute optimal granzyme B expression from S. salivarius-specific CD8 T cells. Also, both the memory and the naive CD8 T cells reacted to S. salivarius-stimulation, with the memory CD8 T cells presenting significantly higher S. salivarius-reactivity. Using M1- and M2-polarized macrophages from circulating monocytes, we found that M1-polarized macrophages, with significantly higher IL-12 expression and significantly lower IL-10 and MHC class II molecule expression, was more effective at promoting granzyme B responses in CD8 T cells, and required CD80/CD86 costimulating molecules for optimal responses. Interestingly, the tumor-associated macrophages (TAMs) from resected tumors presented characteristics of M2-polarized macrophages with high MHC class II expression and low IL-12 secretion. The frequency of tumor-infiltrating S. salivarius-specific cytotoxic CD8 T cell was inversely correlated with the level of IL-10 secretion and the MHC class II molecule expression in autologous TAMs. Together, we demonstrated that monocyte/macrophages presented essential antigen-presentation and costimulatory roles in CD8 T cell-mediated S. salivarius-specific granzyme B responses, and the polarization of macrophages could influence the potency of CD8 T cell responses. Copyright © 2018 Elsevier Inc

  5. Dynamics of Acute Local Inflammatory Response after Autologous Transplantation of Muscle-Derived Cells into the Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Anna Burdzinska

    2014-01-01

    Full Text Available The vast majority of myoblasts transplanted into the skeletal muscle die within the first week after injection. Inflammatory response to the intramuscular cell transfer was studied in allogeneic but not in autologous model. The aim of this study was to evaluate immune reaction to autotransplantation of myogenic cells and to assess its dynamics within the first week after injection. Muscle-derived cells or medium alone was injected into the intact skeletal muscles in autologous model. Tissue samples were collected 1, 3, and 7 days after the procedure. Our analysis revealed the peak increase of the gene expression of all evaluated cytokines (Il-1α, Il-1β, Il-6, Tgf-β, and Tnf-α at day 1. The mRNA level of analyzed cytokines normalized in subsequent time points. The increase of Il-β gene expression was further confirmed at the protein level. Analysis of the tissue sections revealed rapid infiltration of injected cell clusters with neutrophils and macrophages. The inflammatory infiltration was almost completely resolved at day 7. The survived cells were able to participate in the muscle regeneration process. Presented results demonstrate that autotransplanted muscle-derived cells induce classical early immune reaction in the site of injection which may contribute to cellular graft elimination.

  6. Cryopreservation of Autologous Blood (Red Blood Cells, Platelets and Plasma)

    Science.gov (United States)

    Ebine, Kunio

    Prevention of post-transfusion hepatitis is still a problem in cardiovascular surgery. We initiated the cryopreservation of autologous blood for the transfusion in elective cardiovascular surgery since 1981. This study includes 152 surgical cases in which autologous frozen, allogeneic frozen, and/or allogeneic non-frozen blood were used. In the 152 surgical cases, there were 69 cases in which autologous blood only (Group I) was used; 12 cases with autologous and allogeneic frozen blood (Group II); 46 cases with autologous and allgeneic frozen plus allogeneic non-frozen blood (Group III); and 25 cases with allogeneic frozen plus allogeneic non-frozen blood (Group IV). No hepatitis developed in Groups I (0%) and II (0%), but there was positive hepatitis in Groups III (4.3%) and IV (8.0%) . In 357 cases of those who underwent surgery with allogeneic non-frozen whole blood during the same period, the incidence rate of hepatitis was 13.7% (49/357). Patients awaiting elective surgery can store their own blood in the frozen state. Patients who undergo surgery with the cryoautotransfusion will not produce any infections or immunologic reactions as opposed to those who undergo surgery with the allogeneic non-frozen blood.

  7. Spanish Experience in Autologous Chondrocyte Implantation

    Science.gov (United States)

    Pérez-Cachafeiro, Santiago; Ruano-Raviña, Alberto; Couceiro-Follente, José; Benedí-Alcaine, Jose Antonio; Nebot-Sanchis, Ignacio; Casquete-Román, Ciriaco; Bello-Prats, Santiago; Couceiro-Sánchez, Gonzalo; Blanco, Francisco J.

    2010-01-01

    Introduction: The Spanish Ministry of Health commissioned the Galician Agency for Health Technology Assessment to monitor and follow-up Autologous Chondrocyte Implantation (ACI) used to treat chondral lesions of the knee in Spain. The objective of this monitoring was to assess efficacy and safety of the technique. Design: One-hundred and eleven consecutive patients with knee chondral lesions were included in a multi-center study between January 2001 and January 2005. ACI was used in these patients as a second-line treatment option (or a first-line treatment option if the cause was Osteocondritis dissecans). The Cincinnati score and the Short Form 36 (SF-36) questionnaire were used to assess the patients’ self-reported satisfaction with the outcomes of ACI. A descriptive analysis was performed and non-parametric tests were used to establish correlations and compare results among subgroups. A multivariate analysis was also performed to measure the effect of different variables on changes in the condition of the knee. Results: Eighty men (72%) and 31 women (21%) with an age range from 16 to 49 years, underwent ACI surgery. Among these subjects, the most common previous first-line treatment was debridement (64 individuals, 74.4%). The mean size of the lesion treated with ACI was 3.82 cm2, and the most frequent location of the lesion was the inner femoral condyle (53.6%). The patient satisfaction was high or very high in 36 subjects (66.7%). Overall knee joint assessment improved from 4.32 points to 6.78. All SF-36 questionnaire categories improved, notably those related to physical condition. Conclusions: The results of this study indicate that ACI is safe; however, further studies are mandated to assess the efficacy of ACI compared to alternative treatment options. PMID:20148094

  8. Effectiveness of autologous transfusion system in primary total hip and knee arthroplasty.

    LENUS (Irish Health Repository)

    Schneider, Marco M

    2014-01-01

    Autologous transfusion has become a cost-efficient and useful option in the treatment of patients with high blood loss following major orthopaedic surgery. However, the effectiveness of autologous transfusion in total joint replacement remains controversial.

  9. Treatment of osteochondritis dissecans of the femoral condyle with autologous bone grafts and matrix-supported autologous chondrocytes

    Science.gov (United States)

    Bruns, Juergen; Deuretzbacher, Georg; Ruether, Wolfgang; Fuerst, Martin; Niggemeyer, Oliver

    2009-01-01

    The objective of this study was to determine the clinical outcome of combined bone grafting and matrix-supported autologous chondrocyte transplantation in patients with osteochondritis dissecans of the knee. Between January 2003 and March 2005, 21 patients (mean age 29.33 years) with symptomatic osteochondritis dissecans (OCD) of the medial or lateral condyle (grade III or IV) of the knee underwent reconstruction of the joint surface by autologous bone grafts and matrix-supported autologous chondrocyte transplantation. Patients were followed up at three, six, 12 and 36 months to determine outcomes by clinical evaluation based on Lysholm score, IKDC and ICRS score. Clinical results showed a significant improvement of Lysholm-score and IKDC score. With respect to clinical assessment, 18 of 21 patients showed good or excellent results 36 months postoperatively. Our study suggests that treatment of OCD with autologous bone grafts and matrix-supported autologous chondrocytes is a possible alternative to osteochondral cylinder transfer or conventional ACT. PMID:19626325

  10. Improving diagnosis of appendicitis. Early autologous leukocyte scanning.

    Science.gov (United States)

    DeLaney, A R; Raviola, C A; Weber, P N; McDonald, P T; Navarro, D A; Jasko, I

    1989-10-01

    A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of apendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging111 In oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.

  11. [Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation].

    Science.gov (United States)

    Illés, Árpád; Simon, Zsófia; Udvardy, Miklós; Magyari, Ferenc; Jóna, Ádám; Miltényi, Zsófia

    2017-08-01

    Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

  12. Therapeutic Potential of Autologous Stem Cell Transplantation for Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Chaitanya Purandare

    2012-01-01

    Full Text Available Background. Cerebral palsy (CP is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient.

  13. Macrophage Heterogeneity in Respiratory Diseases

    Directory of Open Access Journals (Sweden)

    Carian E. Boorsma

    2013-01-01

    Full Text Available Macrophages are among the most abundant cells in the respiratory tract, and they can have strikingly different phenotypes within this environment. Our knowledge of the different phenotypes and their functions in the lung is sketchy at best, but they appear to be linked to the protection of gas exchange against microbial threats and excessive tissue responses. Phenotypical changes of macrophages within the lung are found in many respiratory diseases including asthma, chronic obstructive pulmonary disease (COPD, and pulmonary fibrosis. This paper will give an overview of what macrophage phenotypes have been described, what their known functions are, what is known about their presence in the different obstructive and restrictive respiratory diseases (asthma, COPD, pulmonary fibrosis, and how they are thought to contribute to the etiology and resolution of these diseases.

  14. Macrophages play a dual role during pulmonary tuberculosis in mice

    NARCIS (Netherlands)

    Leemans, Jaklien C.; Thepen, Theo; Weijer, Sebastiaan; Florquin, Sandrine; van Rooijen, Nico; van de Winkel, Jan G.; van der Poll, Tom

    2005-01-01

    Pulmonary macrophages provide the preferred hiding and replication site of Mycobacterium tuberculosis but display antimicrobial functions. This raises questions regarding the role of macrophages during tuberculosis. We depleted lungs of activated macrophages (activated macrophage(-) mice) and

  15. Labeling of autologous monocytes with 99mTc-HMPAO at very high specific radioactivity

    International Nuclear Information System (INIS)

    Hemert, Formijn J. van; Thurlings, Rogier; Dohmen, Serge E.; Voermans, Carlijn; Tak, Paul P.; Eck-Smit, Berthe L.F. van; Bennink, Roelof J.

    2007-01-01

    Rheumatoid arthritis of joints involves the accumulation of monocyte-derived macrophages in the affected synovial tissue. This process of cell migration can be portrayed scintigraphically in order to monitor noninvasive effects of therapy on the progress of the disease. Scintigraphic detection of inflammation by means of technetium 99m-hexamethylpropylene amine oxime ( 99m Tc-HMPAO)-labeled leukocytes provides a classic example. Present state-of-the-art methods in cell biology allow the isolation of cells like lymphocytes or monocytes, which are less abundant than main blood constituents but, instead, harbor particular functions like specific homing properties. To facilitate scintigraphic imaging of the cell functions involved, the relatively small population of cells must be labeled to radioactive yields as high as possible. We demonstrate that autologous monocytes isolated from 100 ml of peripheral blood can be radiolabeled to a yield of 10 (instead of 1) Bq per cell, allowing scintigraphic analysis of rheumatoid arthritis up to 20 h post injection of patients. The method is based on the instantaneous distribution of lipophilic 99m Tc-HMPAO between the hydrophobic inside of cells and the hydrophilic (aqueous) surrounding of cells, followed by decomposition of the radiopharmaceutical into compounds that are unable to cross the cellular membrane. The procedure provides a method of choice for cell-mediated scintigraphy at low availability of cells with the correct homing properties

  16. Therapeutic effect of autologous dendritic cell vaccine on patients with chronic hepatitis B: a clinical study.

    Science.gov (United States)

    Chen, Min; Li, Yong-Guo; Zhang, Da-Zhi; Wang, Zhi-Yi; Zeng, Wei-Qun; Shi, Xiao-Feng; Guo, Yuan; Guo, Shu-Hua; Ren, Hong

    2005-03-28

    To investigate the therapeutic effect of autologous HBsAg-loaded dendritic cells (DCs) on patients with chronic hepatitis B. Monocytes were isolated from fresh peripheral blood of 19 chronic HBV-infected patients by Ficoll-Hypaque density gradient centrifugation and cultured by plastic-adherence methods. DCs were induced and proliferated in the culture medium with recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF) and human interleukin-4 (rhIL-4). DCs pulsed with HBsAg for twelve hours were injected into patients subcutaneously twice at intervals of two weeks. Two patients received 100 mg oral lamivudine daily for 12 mo at the same time. HBV-DNA and viral markers in sera of patients were tested every two months. By the end of 2003, 11 of 19 (57.9%) patients had a clinical response to DC-treatment. HBeAg of 10 (52.6%) patients became negative, and the copies of HBV-DNA decreased 10(1.77+/-2.39) on average (t = 3.13, Pvaccine induced in vitro can effectively suppress HBV replication, reduce the virus load in sera, eliminate HBeAg and promote HBeAg/anti-HBe transformation. Not only the patients with high serum ALT levels but also those with normal ALT levels can respond to DC vaccine treatment, and the treatment combining DCs with lamivudine can eliminate viruses more effectively.

  17. IAP survivin regulates atherosclerotic macrophage survival

    NARCIS (Netherlands)

    Blanc-Brude, Olivier P.; Teissier, Elisabeth; Castier, Yves; Lesèche, Guy; Bijnens, Ann-Pascal; Daemen, Mat; Staels, Bart; Mallat, Ziad; Tedgui, Alain

    2007-01-01

    Inflammatory macrophage apoptosis is critical to atherosclerotic plaque formation, but its mechanisms remain enigmatic. We hypothesized that inhibitor of apoptosis protein (IAP) survivin regulates macrophage death in atherosclerosis. Western blot analysis revealed discrete survivin expression in

  18. Autologous Mesenchymal Stem Cells in Chronic Stroke

    Directory of Open Access Journals (Sweden)

    Ashu Bhasin

    2011-12-01

    Full Text Available Background: Cell transplantation is a ‘hype and hope’ in the current scenario. It is in the early stage of development with promises to restore function in chronic diseases. Mesenchymal stem cell (MSC transplantation in stroke patients has shown significant improvement by reducing clinical and functional deficits. They are feasible and multipotent and have homing characteristics. This study evaluates the safety, feasibility and efficacy of autologous MSC transplantation in patients with chronic stroke using clinical scores and functional imaging (blood oxygen level-dependent and diffusion tensor imaging techniques. Methods: Twelve chronic stroke patients were recruited; inclusion criteria were stroke lasting 3 months to 1 year, motor strength of hand muscles of at least 2, and NIHSS of 4–15, and patients had to be conscious and able to comprehend. Fugl Meyer (FM, modified Barthel index (mBI, MRC, Ashworth tone grade scale scores and functional imaging scans were assessed at baseline, and after 8 and 24 weeks. Bone marrow was aspirated under aseptic conditions and expansion of MSC took 3 weeks with animal serum-free media (Stem Pro SFM. Six patients were administered a mean of 50–60 × 106 cells i.v. followed by 8 weeks of physiotherapy. Six patients served as controls. This was a non-randomized experimental controlled trial. Results: Clinical and radiological scanning was normal for the stem cell group patients. There was no mortality or cell-related adverse reaction. The laboratory tests on days 1, 3, 5 and 7 were also normal in the MSC group till the last follow-up. The FM and mBI showed a modest increase in the stem cell group compared to controls. There was an increased number of cluster activation of Brodmann areas BA 4 and BA 6 after stem cell infusion compared to controls, indicating neural plasticity. Conclusion: MSC therapy aiming to restore function in stroke is safe and feasible. Further randomized controlled trials are needed

  19. Macrophage Heterogeneity and Plasticity: Impact of Macrophage Biomarkers on Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Joselyn Rojas

    2015-01-01

    Full Text Available Cardiovascular disease (CVD is a global epidemic, currently representing the worldwide leading cause of morbidity and mortality. Atherosclerosis is the fundamental pathophysiologic component of CVD, where the immune system plays an essential role. Monocytes and macrophages are key mediators in this aspect: due to their heterogeneity and plasticity, these cells may act as either pro- or anti-inflammatory mediators. Indeed, monocytes may develop heterogeneous functional phenotypes depending on the predominating pro- or anti-inflammatory microenvironment within the lesion, resulting in classic, intermediate, and non-classic monocytes, each with strikingly differing features. Similarly, macrophages may also adopt heterogeneous profiles being mainly M1 and M2, the former showing a proinflammatory profile while the latter demonstrates anti-inflammatory traits; they are further subdivided in several subtypes with more specialized functions. Furthermore, macrophages may display plasticity by dynamically shifting between phenotypes in response to specific signals. Each of these distinct cell profiles is associated with diverse biomarkers which may be exploited for therapeutic intervention, including IL-10, IL-13, PPAR-γ, LXR, NLRP3 inflammasomes, and microRNAs. Direct modulation of the molecular pathways concerning these potential macrophage-related targets represents a promising field for new therapeutic alternatives in atherosclerosis and CVD.

  20. Role of Osteal Macrophages in Bone Metabolism

    Directory of Open Access Journals (Sweden)

    Sun Wook Cho

    2015-03-01

    Full Text Available Macrophages have been shown to have pleiotropic functions in various pathophysiologies, especially in terms of anti-inflammatory and regenerative activity. Recently, the novel functions of bone marrow resident macrophages (called osteal macrophages were intensively studied in bone development, remodeling and tissue repair processes. This review discusses the current evidence for a role of osteal macrophages in bone modeling, remodeling, and fracture healing processes.

  1. Autologous Immune Enhancement Therapy for Cancer - Our experience since 2004

    Directory of Open Access Journals (Sweden)

    Hiroshi Terunuma

    2012-01-01

    disease (SD, whereas 18 had progressive disease (PD. Disease control rate was 66% including CR, PR and SD. After treatment for six months, the objective responses and disease control rate were 25% and 52%, respectively. There were no adverse effects in any of these patients. [17] Conclusion: Cancer has to be tackled with a multipronged approach and combining NK cell and CTL cell based AIET with conventional modalities of treatments such as Surgery, Chemotherapy and Radiotherapy as well as other modalities like Hyperthermia, Proton Beam therapy and low dose chemotherapy is effective even in advanced cancers which are refractory to conventional therapeutic modalities. References: 1.Rosenberg SA, Rapp HJ. Intralesional immunotherapy of melanoma with BCG. Med Clin North Am. 1976 May;60(3:419-30.2.Mazumder A, Eberlein TJ, Grimm EA, Wilson DJ, Keenan AM, Aamodt R, Rosenberg SA. Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. Cancer. 1984 Feb 15;53(4:896-9053.Takayama T, Sekine T, Makuuchi M, Yamasaki S, Kosuge T, Yamamoto J, Shimada K, Sakamoto M, Hirohashi S, Ohashi Y, Kakizoe T. Adoptive immunotherapy to lower postsurgical recurrence rates of hepatocellular carcinoma: a randomised trial. Lancet. 2000 ;356(9232:802-7.4.Sloan AE, Dansey R, Zamorano L, Barger G, Hamm C, Diaz F, Baynes R, Wood G. Adoptive immunotherapy in patients with recurrent malignant glioma: preliminary results of using autologous whole-tumor vaccine plus granulocyte-macrophage colony-stimulating factor and adoptive transfer of anti-CD3-activated lymphocytes. Neurosurg Focus. 2000; 9(6:e9.5.Recchia F, Candeloro G, Di Staso M, Necozione S, Bisegna R, Bratta M, Tombolini V, Rea S. Maintenance immunotherapy in recurrent or metastatic squamous cell carcinoma of the head and neck. J Immunother. 2008; 31(4:413-9.6.Wright SE, Rewers-Felkins KA, Quinlin IS, Phillips CA, Townsend M, Philip R, Dobrzanski MJ, Lockwood-Cooke PR, Robinson W. Cytotoxic

  2. Heterogeneity of macrophage activation in fish

    NARCIS (Netherlands)

    Forlenza, M.; Fink, I.R.; Raes, G.; Wiegertjes, G.F.

    2011-01-01

    In this review, we focus on four different activation states of fish macrophages. In vitro, stimulation with microbial ligands induces the development of innate activated macrophages whereas classically activated macrophages can be induced by stimulation with LPS in combination with (recombinant)

  3. Characterization of macrophage adhesion molecule

    International Nuclear Information System (INIS)

    Remold-O'Donnell, E.; Savage, B.

    1988-01-01

    Macrophage adhesion molecule (MAM), an abundant surface molecule which functions in the adhesion and spreading of guinea pig macrophages on surfaces, is characterized as a heterodimer of the trypsin- and plasmin-sensitive glycopeptide gp160 (MAM-α) and the glycopeptide gp93 (MAM-β). The density of MAM molecules is estimated at 630,000 per macrophage on the basis of quantitative binding of 125 I-labeled monoclonal antibody. The glycopeptide subunits display microheterogeneity on isoelectrofocusing; the pI is 5.8-6.3 for gp160 (MAM-α) and 6.4-7.0 for gp93 (MAM-β). A neutrophil gp160, gp93 molecule was shown to be indistinguishable from macrophage MAM on the basis of electrophoresis, isoelectrofocusing, and reactivity with 10 monoclonal antibodies. A related heterodimer of gp93 associated with a larger, antigenically different glycopeptide (gp180, gp93)was identified on circulating lymphocytes. Cumulative properties indicate that MAM is the guinea pig analog of human Mo1 and mouse Mac-1

  4. HIV-1 and the macrophage

    NARCIS (Netherlands)

    Bol, Sebastiaan M.; Cobos-Jimenez, Viviana; Kootstra, Neeltje A.; van 't Wout, Angelique B.

    2011-01-01

    Macrophages and CD4(+) T cells are natural target cells for HIV-1, and both cell types contribute to the establishment of the viral reservoir that is responsible for continuous residual virus replication during antiretroviral therapy and viral load rebound upon treatment interruption. Scientific

  5. Resorbable screws for fixation of autologous bone grafts

    NARCIS (Netherlands)

    Raghoebar, GM; Liem, RSB; Bos, RRM; van der Wal, JE; Vissink, A

    The aim of this study was to evaluate the suitability of resorbable screws made of poly (D,L-lactide) acid (PDLLA) for fixation of autologous bone grafts related to graft regeneration and osseointegration of dental implants. In eight edentulous patients suffering from insufficient retention of their

  6. Management of Bone Gaps with Intramedullary Autologous Fibular ...

    African Journals Online (AJOL)

    ... 7 consecutive patients who presented with bone gaps that were managed with intramedullary non vascularised fibular strut graft. Method: Intramedulary Autologous fibular strut graft was used to breach the bone and the whole length augmented with cancellous graft and bridged with bone plate; external fixators or k wires.

  7. Experience with predonated autologous blood transfusion in open ...

    African Journals Online (AJOL)

    Objectives: To find out the practicability, the acceptability, the effectiveness and the safety level of pre-donated, autologous blood transfusion (ABT) in patients who underwent open prostatectomy. Study design: Prospective. Patients and methods: It was a prospective study carried out in Nigeria over a 5-year period.

  8. Review of autologous blood transfusion at the Kenyatta National ...

    African Journals Online (AJOL)

    Objective: This study was performed over a three- month period to establish the pattern of autologous blood transfusion with specific focus on age, sex, type of surgery, duration of hospital stay and religious beliefs. Design: Hospital based prospective study. Setting: The study was conducted at the Kenyatta National Hospital ...

  9. Surgical Patients\\' Knowledge and Acceptance of Autologous Blood ...

    African Journals Online (AJOL)

    Background: Homologous blood transfusion carries a well-documented array of risks especially in an HIV endemic environment like Nigeria. It is therefore imperative to consider other forms of restoring blood volume in surgical patients. Autologous blood transfusion (ABT) is one of the ways the problem of HIV transmission ...

  10. Ten years of preoperative autologous blood donation in Accra ...

    African Journals Online (AJOL)

    Background - Preoperative autologous blood donation (PABD) is utilized to circumvent the use of allogenic blood for various reasons. Objective - To describe the distribution in terms of demographic characteristic, trends in participation and result of screening test of the PABD programme of the Accra Area Blood Center from ...

  11. Autologous epidermal cell suspension: A promising treatment for chronic wounds.

    Science.gov (United States)

    Zhao, Hongliang; Chen, Yan; Zhang, Cuiping; Fu, Xiaobing

    2016-02-01

    Chronic wounds have become an increasing medical and economic problem of aging societies because they are difficult to manage. Skin grafting is an important treatment method for chronic wounds, which are refractory to conservative therapy. The technique involving epidermal cell suspensions was invented to enable the possibility of treating larger wounds with only a small piece of donor skin. Both uncultured and cultured autologous epidermal cell suspensions can be prepared and survive permanently on the wound bed. A systematic search was conducted of EMBASE, Cochrane Library, PubMed and web of science by using Boolean search terms, from the establishment of the database until May 31, 2014. The bibliographies of all retrieved articles in English were searched. The search terms were: (epithelial cell suspension OR keratinocyte suspension) and chronic and wound. From the included, 6 studies are descriptive interventions and discussed the use of autologous keratinocyte suspension to treat 61 patients' chronic wound. The various methods of preparation of epidermal cell suspension are described. The advantages and shortcomings of different carriers for epidermal cell suspensions are also summarised. Both uncultured and cultured autologous epidermal cell suspensions have been used to treat chronic wounds. Although the limitations of these studies include the small number of patient populations with chronic wounds and many important problems that remain to be solved, autologous epidermal cell suspension is a promising treatment for chronic wounds. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  12. Bortezomib consolidation after autologous stem cell transplantation in multiple myeloma

    DEFF Research Database (Denmark)

    Mellqvist, Ulf-Henrik; Gimsing, Peter; Hjertner, Oyvind

    2013-01-01

    The Nordic Myeloma Study Group conducted an open randomized trial to compare bortezomib as consolidation therapy given after high-dose therapy and autologous stem cell transplantation (ASCT) with no consolidation in bortezomib-naive patients with newly diagnosed multiple myeloma. Overall, 370...

  13. Determinants of the Use of Autologous Blood in Elective General ...

    African Journals Online (AJOL)

    Objective: The study reports the 7 year experience of the authors with autologous blood transfusion in elective general surgery using the predeposit method. Material and Method: Patients aged 18 years and older, presenting for elective surgery and for whom blood donation was required were encouraged to predonate one ...

  14. Autologous hematopoietic stem cell transplantation for autoimmune diseases.

    NARCIS (Netherlands)

    Gratwohl, A.; Passweg, J.R.; Bocelli-Tyndall, C.; Fassas, A.; Laar, J.M. van; Farge, D.; Andolina, M.; Arnold, R.; Carreras, E.; Finke, J.; Kotter, I.; Kozak, T.; Lisukov, I.; Lowenberg, B.; Marmont, A.; Moore, J.; Saccardi, R.; Snowden, J.A.; Hoogen, F.H.J. van den; Wulffraat, N.M.; Zhao, X.; Tyndall, A.

    2005-01-01

    Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune

  15. The Influence of Barrier Membranes on Autologous Bone Grafts

    NARCIS (Netherlands)

    Gielkens, P. F. M.; Schortinghuis, J.; de Jong, J. R.; Paans, A. M. J.; Ruben, J. L.; Raghoebar, G. M.; Stegenga, B.; Bos, R. R. M.

    2008-01-01

    In implant dentistry, there is continuing debate regarding whether a barrier membrane should be applied to cover autologous bone grafts in jaw augmentation. A membrane would prevent graft remodeling with resorption and enhance graft incorporation. We hypothesized that membrane coverage does not

  16. Vaccination with apoptosis colorectal cancer cell pulsed autologous ...

    African Journals Online (AJOL)

    To investigate vaccination with apoptosis colorectal cancer (CRC) cell pulsed autologous dendritic cells (DCs) in advanced CRC, 14 patients with advanced colorectal cancer (CRC) were enrolled and treated with DCs vaccine to assess toxicity, tolerability, immune and clinical responses to the vaccine. No severe toxicity ...

  17. Do autologous blood and PRP injections effectively treat tennis elbow?

    Science.gov (United States)

    Widstrom, Luke; Slattengren, Andrew

    2016-09-01

    Both approaches reduce pain, but the improvement with platelet-rich plasma (PRP) is not clinically meaningful. Autologous blood injections (ABIs) are more effective than corticosteroid injections for reducing pain and disability in patients with tennis elbow in both the short and long term.

  18. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala

    2010-04-28

    The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the

  19. Use of containers with sterilizing filter in autologous serum eyedrops.

    Science.gov (United States)

    López-García, José S; García-Lozano, Isabel

    2012-11-01

    To assess the effect of the use of containers with an adapted sterilizing filter on the contamination of autologous serum eyedrops. Prospective, consecutive, comparative, and randomized study. Thirty patients with Sjögren syndrome. One hundred seventy-six autologous serum containers used in home therapy were studied; 48 of them included an adapted filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were conventional containers. Containers equipped with a filter were tested at 7, 14, 21, and 28 days of use, whereas conventional containers were studied after 7 days of use. In addition, testing for contamination was carried out in 14 conventional containers used during in-patient therapy every week for 4 weeks. In all cases, the preparation of the autologous serum was similar. Blood agar and chocolate agar were used as regular culture media for the microbiologic studies, whereas Sabouraud agar with chloramphenicol was the medium for fungal studies. Microbiologic contamination of containers with autologous serum eyedrops. Only one of the containers with an adapted sterilizing filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month of treatment, whereas the contamination rate among conventional containers reached 28.9% after 7 days of treatment. The most frequent germs found in the samples were coagulase-negative Staphylococcus (48.6%). With regard the containers used in the in-patient setting, 2 (14.3%) became contaminated after 2 weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated after 1 month of treatment. Using containers with an adapted filter significantly reduces the contamination rates in autologous serum eyedrops, thus extending the use of such container by the patients for up to 4 weeks with virtually no contamination risks. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  20. Macrophage and T-cell gene expression in a model of early infection with the protozoan Leishmania chagasi.

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    Nicholas A Ettinger

    2008-06-01

    Full Text Available Visceral leishmaniasis is a potentially fatal infectious disease caused by the protozoan parasite Leishmania infantum/chagasi in the New World, or by L. donovani or L. infantum/chagasi in the Old World. Infection leads to a variety of outcomes ranging from asymptomatic infection to active disease, characterized by fevers, cachexia, hepatosplenomegaly and suppressed immune responses. We reasoned that events occurring during the initial few hours when the parasite encounters cells of the innate and adaptive immune systems are likely to influence the eventual immune response that develops. Therefore, we performed gene expression analysis using Affymetrix U133Plus2 microarray chips to investigate a model of early infection with human monocyte-derived macrophages (MDMs challenged with wild-type L. chagasi parasites, with or without subsequent co-culture with Leishmania-naïve, autologous T-cells. Microarray data generated from total RNA were analyzed with software from the Bioconductor Project and functional clustering and pathway analysis were performed with DAVID and Gene Set Enrichment Analysis (GSEA, respectively. Many transcripts were down-regulated by infection in cultures containing macrophages alone, and the pattern indicated a lack of a classically activated phenotype. By contrast, the addition of autologous Leishmania-naïve T cells to infected macrophages resulted in a pattern of gene expression including many markers of type 1 immune cytokine activation (IFN-gamma, IL-6, IL-1alpha, IL-1beta. There was simultaneous up-regulation of a few markers of immune modulation (IL-10 cytokine accumulation; TGF-beta Signaling Pathway. We suggest that the initial encounter between L. chagasi and cells of the innate and adaptive immune system stimulates primarily type 1 immune cytokine responses, despite a lack of classical macrophage activation. This local microenvironment at the site of parasite inoculation may determine the initial course of immune T

  1. Treatment of severe osteochondral defects of the knee by combined autologous bone grafting and autologous chondrocyte implantation using fibrin gel

    NARCIS (Netherlands)

    Konst, Y.E.; Benink, R.J.; Veldstra, R.; van der Krieke, T.J.; Helder, M.N.; van Royen, B.J.

    2012-01-01

    Purpose: Severe symptomatic and unstable osteochondral defects of the knee are difficult to treat. A variety of surgical techniques have been developed. However, the optimal surgical technique is still controversial. We present a novel technique in which autologous bone grafting is combined with

  2. The phenotype of murine wound macrophages.

    Science.gov (United States)

    Daley, Jean M; Brancato, Samielle K; Thomay, Alan A; Reichner, Jonathan S; Albina, Jorge E

    2010-01-01

    The phenotype of wound macrophages has not been studied by direct examination of these cells, yet macrophages recruited to sites of injury are described as alternatively activated macrophages, requiring IL-4 or IL-13 for phenotypic expression. This study characterized wound macrophage phenotype in the PVA sponge wound model in mice. Eighty-five percent of wound macrophages isolated 1 day after injury expressed Gr-1, but only 20% of those isolated at 7 days expressed this antigen. Macrophages from 1-, 3-, and 7-day wounds expressed markers of alternative activation,including mannose receptor, dectin-1, arginase 1,and Ym1, but did not contain iNOS. Day 1 wound macrophages produced more TNF-alpha, more IL-6, and less TGF-beta than Day 7 wound macrophages. Wound macrophages did not produce IL-10. The cytokines considered necessary for alternative activation of macrophages,IL-4 and IL-13, were not detected in the wound environment and were not produced by wound cells.Wound macrophages did not contain PStat6. Wound fluids inhibited IL-13-dependent phosphorylation of Stat6 and contained IL-13Ralpha2, a soluble decoy receptor for IL-13. The phenotype of wound macrophages was not altered in mice lacking IL-4Ralpha, which is required for Stat6-dependent signaling of IL-4 and IL-13.Wound macrophages exhibit a complex phenotype,which includes traits associated with alternative and classical activation and changes as the wound matures.The wound macrophage phenotype does not require IL-4 or IL-13.

  3. Storage xyloglucans: potent macrophages activators.

    Science.gov (United States)

    do Rosário, Marianna Maia Taulois; Kangussu-Marcolino, Mônica Mendes; do Amaral, Alex Evangelista; Noleto, Guilhermina Rodrigues; Petkowicz, Carmen Lúcia de Oliveira

    2011-01-15

    Storage xyloglucans from the seeds of Copaifera langsdorffii, Hymenaea courbaril and Tamarindus indica were obtained by aqueous extraction from the milled and defatted cotyledons, XGC, XGJ and XGT, respectively. The resulting fractions showed similar monosaccharide composition with Glc:Xyl:Gal molar ratios of 2.4:1.5:1.0, 3.8:1.5:1,0 and 3.6:2.4:1.0 for XGC, XGJ and XGT, respectively. High-performance size-exclusion chromatography of the polysaccharides showed unimodal profiles, and the average molar mass (M(w)) was obtained for XGC (9.6 × 10⁵ g/mol), XGJ (9.1 × 10⁵ g/mol) and XGT (7.3 × 10⁵ g/mol). The immunomodulatory effects of the xyloglucans on peritoneal macrophages were evaluated. Phagocytic activity was observed in macrophages treated with XGT. The effect of XGT was tested on the production of O₂(.-) and NO. At 25 μg/ml XGT caused a 100% increase in NO production when compared to the control group; however, it did not affect O₂(.-) production in the absence of PMA. The production of TNF-α, interleukins 1β and 6 by macrophages in the presence of the xyloglucans was evaluated. The polysaccharides affected the production of the cytokines by macrophages to different degrees. XGC caused an enhancement of IL-1β and TNF-α production, compared to the other xyloglucans. For IL-6 production, XGT gave greater stimulation than XGC and XGJ, reaching 87% at 50 μg/ml. XGJ promoted a statistically significant effect on all cytokine productions tested. The results indicate that the xyloglucans from C. langsdorffii, H. courbaril and T. indica can be classified as biological response modifiers (BRM). Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Effects of ischemia on lung macrophages.

    Directory of Open Access Journals (Sweden)

    Aigul Moldobaeva

    Full Text Available Angiogenesis after pulmonary ischemia is initiated by reactive O(2 species and is dependent on CXC chemokine growth factors, and its magnitude is correlated with the number of lavaged macrophages. After complete obstruction of the left pulmonary artery in mice, the left lung is isolated from the peripheral circulation until 5-7 days later, when a new systemic vasculature invades the lung parenchyma. Consequently, this model offers a unique opportunity to study the differentiation and/or proliferation of monocyte-derived cells within the lung. In this study, we questioned whether macrophage subpopulations were differentially expressed and which subset contributed to growth factor release. We characterized the change in number of all macrophages (MHCII(int, CD11C+, alveolar macrophages (MHCII(int, CD11C+, CD11B- and mature lung macrophages (MHCII(int, CD11C+, CD11B+ in left lungs from mice immediately (0 h or 24 h after left pulmonary artery ligation (LPAL. In left lung homogenates, only lung macrophages increased 24 h after LPAL (vs. 0 h; p<0.05. No changes in proliferation were seen in any subset by PCNA expression (0 h vs. 24 h lungs. When the number of monocytic cells was reduced with clodronate liposomes, systemic blood flow to the left lung 14 days after LPAL decreased by 42% (p<0.01 compared to vehicle controls. Furthermore, when alveolar macrophages and lung macrophages were sorted and studied in vitro, only lung macrophages secreted the chemokine MIP-2α (ELISA. These data suggest that ischemic stress within the lung contributes to the differentiation of immature monocytes to lung macrophages within the first 24 h after LPAL. Lung macrophages but not alveolar macrophages increase and secrete the proangiogenic chemokine MIP-2α. Overall, an increase in the number of lung macrophages appears to be critical for neovascularization in the lung, since clodronate treatment decreased their number and attenuated functional angiogenesis.

  5. Bio-artificial pleura using an autologous dermal fibroblast sheet

    Science.gov (United States)

    Kanzaki, Masato; Takagi, Ryo; Washio, Kaoru; Kokubo, Mami; Yamato, Masayuki

    2017-10-01

    Air leaks (ALs) are observed after pulmonary resections, and without proper treatment, can produce severe complications. AL prevention is a critical objective for managing patients after pulmonary resection. This study applied autologous dermal fibroblast sheets (DFS) to close ALs. For sealing ALs in a 44-year-old male human patient with multiple bullae, a 5 × 15-mm section of skin was surgically excised. From this skin specimen, primary dermal fibroblasts were isolated and cultured for 4 weeks to produce DFSs that were harvested after a 10-day culture. ALs were completely sealed using surgical placement of these autologous DFSs. DFS were found to be a durable long-term AL sealant, exhibiting requisite flexibility, elasticity, durability, biocompatibility, and usability, resulting reliable AL closure. DFS should prove to be an extremely useful tissue-engineered pleura substitute.

  6. Autologous Fat Transfer in a Patient with Lupus Erythematosus Profundus

    Directory of Open Access Journals (Sweden)

    Jimi Yoon

    2012-10-01

    Full Text Available Lupus erythematosus profundus, a form of chronic cutaneous lupus erythematosus, is a rare inflammatory disease involving in the lower dermis and subcutaneous tissues. It primarily affects the head, proximal upper arms, trunk, thighs, and presents as firm nodules, 1 to 3 cm in diameter. The overlying skin often becomes attached to the subcutaneous nodules and is drawn inward to produce deep, saucerized depressions. We present a rare case of lupus erythematosus profundus treated with autologous fat transfer.

  7. Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

    Directory of Open Access Journals (Sweden)

    Grace E Cooper

    Full Text Available Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function. Human monocyte-derived macrophages (MDM were exposed to H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV or UV-irradiated virus. No infection of MDM was seen upon exposure to UV-irradiated virus but incubation with live X31 or M37 resulted in significant levels of viral detection by flow cytometry or RT-PCR respectively. Infection resulted in significantly diminished uptake of S. pneumoniae by MDM and significantly decreased expression of CD36 at both the cell surface and mRNA level. Concurrently, there was a significant increase in IFNβ gene expression in response to infection and we observed a significant decrease in bacterial phagocytosis (p = 0.031 and CD36 gene expression (p = 0.031 by MDM cultured for 24 h in 50IU/ml IFNβ. Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was mimicked by transfection reagent alone. When MDM were incubated with CD36 blocking antibodies no effect on phagocytic ability was observed. These data indicate that autologous IFNβ production by virally-infected cells can inhibit bacterial phagocytosis, but that decreased CD36 expression by these cells does not play a major role in this functional deficiency.

  8. Wound Macrophages as Key Regulators of Repair

    Science.gov (United States)

    Brancato, Samielle K.; Albina, Jorge E.

    2011-01-01

    Recent results call for the reexamination of the phenotype of wound macrophages and their role in tissue repair. These results include the characterization of distinct circulating monocyte populations with temporally restricted capacities to migrate into wounds and the observation that the phenotype of macrophages isolated from murine wounds partially reflects those of their precursor monocytes, changes with time, and does not conform to current macrophage classifications. Moreover, findings in genetically modified mice lacking macrophages have confirmed that these cells are essential to normal wound healing because their depletion results in retarded and abnormal repair. This mini-review focuses on current knowledge of the phenotype of wound macrophages, their origin and fate, and the specific macrophage functions that underlie their reparative role in injured tissues, including the regulation of the cellular infiltration of the wound and the production of transforming growth factor-β and vascular endothelial growth factor. PMID:21224038

  9. Herpes zoster after autologous hematopoietic stem cell transplantation

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    Kelli Borges dos Santos

    Full Text Available ABSTRACT Background: The autologous hematopoietic stem cell transplantation procedure involves immunosuppression of the patient. Thus, the patient has an elevated risk for several diseases, such as infections with the varicella-zoster virus. Prevention protocols have been proposed based on the use of acyclovir from the first day of conditioning, and maintaining this drug for 30-100 days after the procedure or for as much as one year. The objective of this work was to evaluate the incidence of herpes zoster after autologous transplantations related to the early suspension of acyclovir. Methods: A retrospective study was carried out based on the collection of data from 231 medical records of transplant patients in the Bone Marrow Transplant Unit of the teaching hospital of the Universidade Federal de Juiz de Fora in the period between 2004 and 2014. Results: Fourteen (6.1% patients had herpes zoster in the post-transplant period on average within six months of the procedure. Patients with multiple myeloma (64.3% were the most affected. There was a statistically significant difference in the age of the patients, with older individuals having a greater chance of developing the infection (p-value = 0.002. There were no significant differences for the other variables analyzed. Conclusion: The early suspension of acyclovir can be safe in patients who receive autologous hematopoietic stem cell transplants. However some groups may benefit from extended prophylaxis with acyclovir, particularly older patients and patients with multiple myeloma.

  10. Gallium-67 scanning and autologous transplantation for lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Mansberg, R.; Bautovich, G.J.; Forsyth, C.J.; Joshua, D.E.; Gibson, J. [Royal Prince Alfred Hospital, Sydney, NSW (Australia). Department of Nuclear Medicine and Haematology

    1998-06-01

    Full text: Gallium-67 ({sup 67}Ga) scanning in the malignant Iymphomas has been performed for over 20 years. Its major contributions are in staging and in detecting relapse, residual or progressive disease. Autologous bone marrow or peripheral blood stem cell transplantation is now an accepted therapy for refractory and relapsed Iymphoma. Between May 1991 and December 1995, 19 patients underwent autologous bone marrow or peripheral blood stem cell transplantation for Non-Hodgkin`s Iymphoma or Hodgkin`s disease. Five patients had high grade Non-Hodgkin`s Iymphoma with widespread disease and did not undergo {sup 67}Ga scanning. There was one transplant related death. Thirteen patients had {sup 67}Ga scanning pre- and post-transplantation. Six patients remained in clinical remission with no evidence of gallium avid active disease at a median of 11 months (range 3 to 19 months) post-transplant. Five of these patients had intermediate grade Non-Hodgkin`s Iymphoma and one had Hodgkin`s disease. The other seven patients all demonstrated evidence of active disease on {sup 67}Ga scanning and subsequent clinical relapse. In all patients shown to have {sup 67}Ga avid disease pre-transplant, {sup 67}Ga scanning post-transplant is useful in detecting relapse These results suggest that {sup 67}Ga avid disease pre-transplant, {sup 67}Ga scanning post-autologous transplantation as it is for conventional chemotherapy and radiotherapy

  11. Gallium-67 scanning and autologous transplantation for lymphoma

    International Nuclear Information System (INIS)

    Mansberg, R.; Bautovich, G.J.; Forsyth, C.J.; Joshua, D.E.; Gibson, J.

    1998-01-01

    Full text: Gallium-67 ( 67 Ga) scanning in the malignant Iymphomas has been performed for over 20 years. Its major contributions are in staging and in detecting relapse, residual or progressive disease. Autologous bone marrow or peripheral blood stem cell transplantation is now an accepted therapy for refractory and relapsed Iymphoma. Between May 1991 and December 1995, 19 patients underwent autologous bone marrow or peripheral blood stem cell transplantation for Non-Hodgkin's Iymphoma or Hodgkin's disease. Five patients had high grade Non-Hodgkin's Iymphoma with widespread disease and did not undergo 67 Ga scanning. There was one transplant related death. Thirteen patients had 67 Ga scanning pre- and post-transplantation. Six patients remained in clinical remission with no evidence of gallium avid active disease at a median of 11 months (range 3 to 19 months) post-transplant. Five of these patients had intermediate grade Non-Hodgkin's Iymphoma and one had Hodgkin's disease. The other seven patients all demonstrated evidence of active disease on 67 Ga scanning and subsequent clinical relapse. In all patients shown to have 67 Ga avid disease pre-transplant, 67 Ga scanning post-transplant is useful in detecting relapse These results suggest that 67 Ga avid disease pre-transplant, 67 Ga scanning post-autologous transplantation as it is for conventional chemotherapy and radiotherapy

  12. Tissue-engineered autologous grafts for facial bone reconstruction.

    Science.gov (United States)

    Bhumiratana, Sarindr; Bernhard, Jonathan C; Alfi, David M; Yeager, Keith; Eton, Ryan E; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M; Lopez, Mandi J; Eisig, Sidney B; Vunjak-Novakovic, Gordana

    2016-06-15

    Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care-the use of bone harvested from another region in the body-has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material and crafted it into an anatomically correct shape using image-guided micromilling to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either nonseeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. Copyright © 2016, American Association for the Advancement of Science.

  13. Autologous Matrix-Induced Chondrogenesis in the Knee: A Review.

    Science.gov (United States)

    Lee, Yee Han Dave; Suzer, Ferzan; Thermann, Hajo

    2014-07-01

    Autologous matrix-induced chondrogenesis (AMIC) is a 1-step cartilage restoration technique that combines microfracture with the use of an exogenous scaffold. This matrix covers and mechanically stabilizes the clot. There have been an increasing number of studies performed related to the AMIC technique and an update of its use and results is warranted. Using the PubMed database, a literature search was performed using the terms "AMIC" or "Autologous Matrix Induced Chondrogenesis." A total of 19 basic science and clinical articles were identified. Ten studies that were published on the use of AMIC for knee chondral defects were identified and the results of 219 patients were analyzed. The improvements in Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee Subjective, Lysholm and Tegner scores at 2 years were comparable to the published results from autologous chondrocyte implantation (ACI) and matrix ACI techniques for cartilage repair. Our systematic review of the current state of the AMIC technique suggests that it is a promising 1-stage cartilage repair technique. The short-term clinical outcomes and magnetic resonance imaging results are comparable to other cell-based methods. Further studies with AMIC in randomized studies versus other repair techniques such as ACI are needed in the future.

  14. High-resolution transcriptome of human macrophages.

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    Marc Beyer

    Full Text Available Macrophages are dynamic cells integrating signals from their microenvironment to develop specific functional responses. Although, microarray-based transcriptional profiling has established transcriptional reprogramming as an important mechanism for signal integration and cell function of macrophages, current knowledge on transcriptional regulation of human macrophages is far from complete. To discover novel marker genes, an area of great need particularly in human macrophage biology but also to generate a much more thorough transcriptome of human M1- and M1-like macrophages, we performed RNA sequencing (RNA-seq of human macrophages. Using this approach we can now provide a high-resolution transcriptome profile of human macrophages under classical (M1-like and alternative (M2-like polarization conditions and demonstrate a dynamic range exceeding observations obtained by previous technologies, resulting in a more comprehensive understanding of the transcriptome of human macrophages. Using this approach, we identify important gene clusters so far not appreciated by standard microarray techniques. In addition, we were able to detect differential promoter usage, alternative transcription start sites, and different coding sequences for 57 gene loci in human macrophages. Moreover, this approach led to the identification of novel M1-associated (CD120b, TLR2, SLAMF7 as well as M2-associated (CD1a, CD1b, CD93, CD226 cell surface markers. Taken together, these data support that high-resolution transcriptome profiling of human macrophages by RNA-seq leads to a better understanding of macrophage function and will form the basis for a better characterization of macrophages in human health and disease.

  15. Quantitative GPCR and ion channel transcriptomics in primary alveolar macrophages and macrophage surrogates

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    Groot-Kormelink Paul J

    2012-10-01

    Full Text Available Abstract Background Alveolar macrophages are one of the first lines of defence against invading pathogens and play a central role in modulating both the innate and acquired immune systems. By responding to endogenous stimuli within the lung, alveolar macrophages contribute towards the regulation of the local inflammatory microenvironment, the initiation of wound healing and the pathogenesis of viral and bacterial infections. Despite the availability of protocols for isolating primary alveolar macrophages from the lung these cells remain recalcitrant to expansion in-vitro and therefore surrogate cell types, such as monocyte derived macrophages and phorbol ester-differentiated cell lines (e.g. U937, THP-1, HL60 are frequently used to model macrophage function. Methods The availability of high throughput gene expression technologies for accurate quantification of transcript levels enables the re-evaluation of these surrogate cell types for use as cellular models of the alveolar macrophage. Utilising high-throughput TaqMan arrays and focussing on dynamically regulated families of integral membrane proteins, we explore the similarities and differences in G-protein coupled receptor (GPCR and ion channel expression in alveolar macrophages and their widely used surrogates. Results The complete non-sensory GPCR and ion channel transcriptome is described for primary alveolar macrophages and macrophage surrogates. The expression of numerous GPCRs and ion channels whose expression were hitherto not described in human alveolar macrophages are compared across primary macrophages and commonly used macrophage cell models. Several membrane proteins known to have critical roles in regulating macrophage function, including CXCR6, CCR8 and TRPV4, were found to be highly expressed in macrophages but not expressed in PMA-differentiated surrogates. Conclusions The data described in this report provides insight into the appropriate choice of cell models for

  16. Macrophage and nerve interaction in endometriosis.

    Science.gov (United States)

    Wu, Jinjie; Xie, Hongyu; Yao, Shuzhong; Liang, Yanchun

    2017-03-14

    Dysregulation of the immune system in endometriotic milieus has been considered to play a pivotal role in the pathogenesis of endometriosis. Macrophage recruitment and nerve fiber infiltration are the two major characteristics of this aberrant immune environment. First, the recruitment of macrophages and their polarization phenotype within the endometriotic lesion have been demonstrated to facilitate the development and maintenance of endometriosis. M1 phenotype of macrophages has the capacity to secrete multiple cytokines for inflammatory response, while M2 macrophage possesses an opposite property that can mediate the process of immunosuppression and neuroangiogenesis. Upon secretion of multiple abnormal signal molecules by the endometriotic lesion, macrophages could alter their location and phenotype. These changes facilitate the accommodation of the aberrant microenvironment and the exacerbation of disease progression. Second, the infiltration of nerve fibers and their abnormal distribution are proved to be involved in the generation of endometriosis-associated pain and inflammatory response. An imbalance in sensory and sympathetic innervation and the abnormal secretion of different cytokines could mediate neurogenesis and subsequent peripheral neuroinflammation in endometriosis. Although endometriosis creates an inflammatory milieu promoting macrophage infiltration and an imbalanced innervation, interaction between macrophages and nerve fibers in this process remains unknown. The aim of this review is to highlight the role of macrophage and nerve interaction in endometriosis, where macrophage recruitment and neurogenesis can be the underlying mechanism of neuroinflammation and pathogenesis of endometriosis.

  17. Development and maintainance of resident macrophages

    Science.gov (United States)

    Perdiguero, Elisa Gomez; Geissmann, Frederic

    2016-01-01

    The molecular and cellular mechanisms that underlie the many roles of macrophages in health and disease states in vivo remain poorly understood. The purpose of this Review is to present and discuss current knowledge on the developmental biology of macrophages, as it underlies the concept of a layered myeloid system composed of ‘resident’ macrophages that mostly originate from yolk sac progenitors and of ‘passenger’ or ‘transitory’ myeloid cells that originate and renew from bone marrow hematopoietic stem cells, and to provide a framework to investigate the functions of macrophages in vivo. PMID:26681456

  18. Macrophage Plasticity in Skeletal Muscle Repair

    Directory of Open Access Journals (Sweden)

    Elena Rigamonti

    2014-01-01

    Full Text Available Macrophages are one of the first barriers of host defence against pathogens. Beyond their role in innate immunity, macrophages play increasingly defined roles in orchestrating the healing of various injured tissues. Perturbations of macrophage function and/or activation may result in impaired regeneration and fibrosis deposition as described in several chronic pathological diseases. Heterogeneity and plasticity have been demonstrated to be hallmarks of macrophages. In response to environmental cues they display a proinflammatory (M1 or an alternative anti-inflammatory (M2 phenotype. A lot of evidence demonstrated that after acute injury M1 macrophages infiltrate early to promote the clearance of necrotic debris, whereas M2 macrophages appear later to sustain tissue healing. Whether the sequential presence of two different macrophage populations results from a dynamic shift in macrophage polarization or from the recruitment of new circulating monocytes is a subject of ongoing debate. In this paper, we discuss the current available information about the role that different phenotypes of macrophages plays after injury and during the remodelling phase in different tissue types, with particular attention to the skeletal muscle.

  19. Macrophage antioxidant protection within atherosclerotic plaques.

    Science.gov (United States)

    Gieseg, Steven P; Leake, David S; Flavall, Elizabeth M; Amit, Zunika; Reid, Linzi; Yang, Ya-Ting

    2009-01-01

    Macrophage cells within inflammatory lesions are exposed to a wide range of degrading and cytotoxic molecules including reactive oxygen species. Unlike neutrophils, macrophages do not normally die in this environment but continue to generate oxidants, phagocytose cellular remains, and release a range of cyto-active agents which modulate the immune response. It is this potential of the macrophage cell to survive in an oxidative environment that allows the growth and complexity of advanced atherosclerotic plaques. This review will examine the oxidants encountered by macrophages within an atherosclerotic plaque and describe some of the potential antioxidant mechanisms which enable macrophages to function within inflammatory lesions. Ascorbate, a-tocopherol, and glutathione appear to be central to the protection of macrophages yet additional antioxidant mechanisms appear to be involved. Gamma-Interferon causes macrophages to generate 7,8-dihydroneopterin, neopterin and 3-hydroxyanthranilic acid both of which have antioxidant properties. Manganese superoxide dismutase is also upregulated in macrophages. The evidence that these antioxidants provide further protection, so allowing the macrophage cells to survive within sites of chronic inflammation such as atherosclerotic plaques, will be described.

  20. Treatment of Adult Severe Traumatic Brain Injury Using Autologous Bone Marrow Mononuclear Cells

    Science.gov (United States)

    2014-12-01

    Our primary hypothesis is that bone marrow mononuclear cell (BMMNC) autologous transplantation after TBI is safe. Our secondary hypothesis is that...AD_________________ Award Number: W81XWH-11-1-0460 TITLE: TREATMENT OF ADULT SEVERE TRAUMATIC BRAIN INJURY USING AUTOLOGOUS BONE MARROW ... AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS” 5a. CONTRACT NUMBER 5b. GRANT NUMBER: W81XWH-11-1-0460 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Charles S. Cox

  1. DMPD: Iron regulation of hepatic macrophage TNFalpha expression. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11841920 Iron regulation of hepatic macrophage TNFalpha expression. Tsukamoto H. Fr...ee Radic Biol Med. 2002 Feb 15;32(4):309-13. (.png) (.svg) (.html) (.csml) Show Iron regulation of hepatic m...acrophage TNFalpha expression. PubmedID 11841920 Title Iron regulation of hepatic macrophage TNFalpha expres

  2. DMPD: Nuclear receptors in macrophages: a link between metabolism and inflammation. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18022390 Nuclear receptors in macrophages: a link between metabolism and inflammati... Show Nuclear receptors in macrophages: a link between metabolism and inflammation. PubmedID 18022390 Title ...Nuclear receptors in macrophages: a link between metabolism and inflammation. Aut

  3. Evidence for M2 macrophages in granulomas from pulmonary sarcoidosis : a new aspect of macrophage heterogeneity

    NARCIS (Netherlands)

    Shamaei, Masoud; Mortaz, Esmaeil; Pourabdollah, Mihan; Garssen, Johan; Tabarsi, Payam; Velayati, Aliakbar; Adcock, Ian M

    BACKGROUND: Sarcoidosis is a granulomatous disease of unknown etiology. Macrophages play a key role in granuloma formation with the T cells, having a significant impact on macrophage polarization (M1 and M2) and the cellular composition of the granuloma. This study evaluates macrophage polarization

  4. DMPD: Macrophage activation by endogenous danger signals. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18161744 Macrophage activation by endogenous danger signals. Zhang X, Mosser DM. J ...Pathol. 2008 Jan;214(2):161-78. (.png) (.svg) (.html) (.csml) Show Macrophage activation by endogenous dange...r signals. PubmedID 18161744 Title Macrophage activation by endogenous danger signals. Authors Zhang X, Moss

  5. DMPD: Regulation of endogenous apolipoprotein E secretion by macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18388328 Regulation of endogenous apolipoprotein E secretion by macrophages. Kockx ...svg) (.html) (.csml) Show Regulation of endogenous apolipoprotein E secretion by macrophages. PubmedID 18388...328 Title Regulation of endogenous apolipoprotein E secretion by macrophages. Aut

  6. DMPD: Macrophage differentiation and function in health and disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18251777 Macrophage differentiation and function in health and disease. Naito M. Pa...thol Int. 2008 Mar;58(3):143-55. (.png) (.svg) (.html) (.csml) Show Macrophage differentiation and function in health... and disease. PubmedID 18251777 Title Macrophage differentiation and function in health and disease

  7. DMPD: Macrophage migration inhibitory factor and host innate immune responses tomicrobes. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14620137 Macrophage migration inhibitory factor and host innate immune responses to...microbes. Calandra T. Scand J Infect Dis. 2003;35(9):573-6. (.png) (.svg) (.html) (.csml) Show Macrophage migration... inhibitory factor and host innate immune responses tomicrobes. PubmedID 14620137 Title Macrophage migration

  8. DMPD: Cellular signaling in macrophage migration and chemotaxis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11073096 Cellular signaling in macrophage migration and chemotaxis. Jones GE. J Leu...koc Biol. 2000 Nov;68(5):593-602. (.png) (.svg) (.html) (.csml) Show Cellular signaling in macrophage migration... and chemotaxis. PubmedID 11073096 Title Cellular signaling in macrophage migration and chemotaxis. Autho

  9. Siglec-1 initiates formation of the virus-containing compartment and enhances macrophage-to-T cell transmission of HIV-1.

    Directory of Open Access Journals (Sweden)

    Jason E Hammonds

    2017-01-01

    Full Text Available HIV-1 particles assemble and bud from the plasma membrane of infected T lymphocytes. Infected macrophages, in contrast, accumulate particles within an apparent intracellular compartment known as the virus-containing compartment or VCC. Many aspects of the formation and function of the VCC remain unclear. Here we demonstrate that VCC formation does not actually require infection of the macrophage, but can be reproduced through the exogenous addition of non-infectious virus-like particles or infectious virions to macrophage cultures. Particles were captured by Siglec-1, a prominent cell surface lectin that attaches to gangliosides on the lipid envelope of the virus. VCCs formed within infected macrophages were readily targeted by the addition of ganglioside-containing virus-like particles to the extracellular media. Depletion of Siglec-1 from the macrophage or depletion of gangliosides from viral particles prevented particle uptake into the VCC and resulted in substantial reductions of VCC volume. Furthermore, Siglec-1-mediated virion capture and subsequent VCC formation was required for efficient trans-infection of autologous T cells. Our results help to define the nature of this intracellular compartment, arguing that it is a compartment formed by particle uptake from the periphery, and that this compartment can readily transmit virus to target T lymphocytes. Inhibiting or eliminating the VCC may be an important component of strategies to reduce HIV transmission and to eradicate HIV reservoirs.

  10. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

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    Jaewoo Pak

    2016-08-01

    Full Text Available This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs and homogenized extracellular matrix (ECM in the form of adipose stromal vascular fraction (SVF, along with hyaluronic acid (HA and platelet-rich plasma (PRP activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI data, functional rating index, range of motion (ROM, and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees.

  11. Nicotine Impairs Macrophage Control of Mycobacterium tuberculosis.

    Science.gov (United States)

    Bai, Xiyuan; Stitzel, Jerry A; Bai, An; Zambrano, Cristian A; Phillips, Matthew; Marrack, Philippa; Chan, Edward D

    2017-09-01

    Pure nicotine impairs macrophage killing of Mycobacterium tuberculosis (MTB), but it is not known whether the nicotine component in cigarette smoke (CS) plays a role. Moreover, the mechanisms by which nicotine impairs macrophage immunity against MTB have not been explored. To neutralize the effects of nicotine in CS extract, we used a competitive inhibitor to the nicotinic acetylcholine receptor (nAChR)-mecamylamine-as well as macrophages derived from mice with genetic disruption of specific subunits of nAChR. We also determined whether nicotine impaired macrophage autophagy and whether nicotine-exposed T regulatory cells (Tregs) could subvert macrophage anti-MTB immunity. Mecamylamine reduced the CS extract increase in MTB burden by 43%. CS extract increase in MTB was also significantly attenuated in macrophages from mice with genetic disruption of either the α7, β2, or β4 subunit of nAChR. Nicotine inhibited autophagosome formation in MTB-infected THP-1 cells and primary murine alveolar macrophages, as well as increased the intracellular MTB burden. Nicotine increased migration of THP-1 cells, consistent with the increased number of macrophages found in the lungs of smokers. Nicotine induced Tregs to produce transforming growth factor-β. Naive mouse macrophages co-cultured with nicotine-exposed Tregs had significantly greater numbers of viable MTB recovered with increased IL-10 production and urea production, but no difference in secreted nitric oxide as compared with macrophages cocultured with unexposed Tregs. We conclude that nicotine in CS plays an important role in subverting macrophage control of MTB infection.

  12. Mycobacteria, Metals, and the Macrophage

    Science.gov (United States)

    Niederweis, Michael; Wolschendorf, Frank; Mitra, Avishek; Neyrolles, Olivier

    2015-01-01

    Summary Mycobacterium tuberculosis is a facultative intracellular pathogen that thrives inside host macrophages. A key trait of M. tuberculosis is to exploit and manipulate metal cation trafficking inside infected macrophages to ensure survival and replication inside the phagosome. Here we describe the recent fascinating discoveries that the mammalian immune system responds to infections with M. tuberculosis by overloading the phagosome with copper and zinc, two metals which are essential nutrients in small quantities but are toxic in excess. M. tuberculosis has developed multi-faceted resistance mechanisms to protect itself from metal toxicity including control of uptake, sequestration inside the cell, oxidation, and efflux. The host response to infections combines this metal poisoning strategy with nutritional immunity mechanisms that deprive M. tuberculosis from metals such as iron and manganese to prevent bacterial replication. Both immune mechanisms rely on the translocation of metal transporter proteins to the phagosomal membrane during the maturation process of the phagosome. This review summarizes these recent findings and discusses how metal-targeted approaches might complement existing TB chemotherapeutic regimens with novel anti-infective therapies. PMID:25703564

  13. A broken krebs cycle in macrophages.

    Science.gov (United States)

    O'Neill, Luke A J

    2015-03-17

    Macrophages undergo metabolic rewiring during polarization but details of this process are unclear. In this issue of Immunity, Jha et al. (2015) report a systems approach for unbiased analysis of cellular metabolism that reveals key metabolites and metabolic pathways required for distinct macrophage polarization states. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Macrophages in skin injury and repair

    NARCIS (Netherlands)

    Mahdavian Delavary, B.; van der Veer, W.M.; van Egmond, M.; Niessen, F.B.; Beelen, R.H.J.

    2011-01-01

    After recruitment to the wound bed, monocytes differentiate into macrophages. Macrophages play a central role in all stages of wound healing and orchestrate the wound healing process. Their functional phenotype is dependent on the wound microenvironment, which changes during healing, hereby altering

  15. Metabolic regulation of macrophages in tissues

    NARCIS (Netherlands)

    van den Bossche, Jan; Saraber, Doina L.

    2018-01-01

    Macrophages are innate immune cells that provide host defense and have tissue-specific roles in the maintenance of organ homeostasis and integrity. In most cases macrophages keep us healthy but when their balanced response to damage or homeostatic signals is perturbed, they can drive chronic

  16. Macrophages Promote Axon Regeneration with Concurrent Neurotoxicity

    NARCIS (Netherlands)

    Gensel, J.C.; Nakamura, S.; Guan, Z.; Rooijen, van N.; Ankeny, D.P.; Popovich, P.G.

    2009-01-01

    Activated macrophages can promote regeneration of CNS axons. However, macrophages also release factors that kill neurons. These opposing functions are likely induced simultaneously but are rarely considered together in the same experimental preparation. A goal of this study was to unequivocally

  17. Human malignant astrocytes express macrophage phenotype

    NARCIS (Netherlands)

    Leenstra, S.; Das, P. K.; Troost, D.; de Boer, O. J.; Bosch, D. A.

    1995-01-01

    Six well-characterized specimens of cultured astrocytoma cells were investigated with a panel of macrophage markers. Our results show that the macrophage markers OKM-1(CD11b), OKM5(CD36), EBM11(CD68), HAM56, Factor 13, alpha-1-antichymotrypsin, alpha-1-antitrypsin, ferritin and lysozyme are clearly

  18. Macrophage polarization: the epigenetic point of view

    NARCIS (Netherlands)

    van den Bossche, Jan; Neele, Annette E.; Hoeksema, Marten A.; de Winther, Menno P. J.

    2014-01-01

    The first functions of macrophages to be identified by Metchnikoff were phagocytosis and microbial killing. Although these are important features, macrophages are functionally very complex and involved in virtually all aspects of life, from immunity and host defense, to homeostasis, tissue repair

  19. Unraveling Macrophage Heterogeneity in Erythroblastic Islands

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    Katie Giger Seu

    2017-09-01

    Full Text Available Mammalian erythropoiesis occurs within erythroblastic islands (EBIs, niches where maturing erythroblasts interact closely with a central macrophage. While it is generally accepted that EBI macrophages play an important role in erythropoiesis, thorough investigation of the mechanisms by which they support erythropoiesis is limited largely by inability to identify and isolate the specific macrophage sub-population that constitute the EBI. Early studies utilized immunohistochemistry or immunofluorescence to study EBI morphology and structure, while more recent efforts have used flow cytometry for high-throughput quantitative characterization of EBIs and their central macrophages. However, these approaches based on the expectation that EBI macrophages are a homogeneous population (F4/80+/CD169+/VCAM-1+ for example provide an incomplete picture and potentially overlook critical information about the nature and biology of the islands and their central macrophages. Here, we present a novel method for analysis of EBI macrophages from hematopoietic tissues of mice and rats using multispectral imaging flow cytometry (IFC, which combines the high-throughput advantage of flow cytometry with the morphological and fluorescence features derived from microscopy. This method provides both quantitative analysis of EBIs, as well as structural and morphological details of the central macrophages and associated cells. Importantly, the images, combined with quantitative software features, can be used to evaluate co-expression of phenotypic markers which is crucial since some antigens used to identify macrophages (e.g., F4/80 and CD11b can be expressed on non-erythroid cells associated with the islands instead of, or in addition to the central macrophage itself. We have used this method to analyze native EBIs from different hematopoietic tissues and evaluated the expression of several markers that have been previously reported to be expressed on EBI macrophages. We

  20. Macrophage Polarization in Health and Disease

    Science.gov (United States)

    Cassetta, Luca; Cassol, Edana; Poli, Guido

    2011-01-01

    Macrophages are terminally differentiated cells of the mononuclear phagocyte system that also encompasses dendritic cells, circulating blood monocytes, and committed myeloid progenitor cells in the bone marrow. Both macrophages and their monocytic precursors can change their functional state in response to microenvironmental cues exhibiting a marked heterogeneity. However, there are still uncertainties regarding distinct expression patterns of surface markers that clearly define macrophage subsets, particularly in the case of human macrophages. In addition to their tissue distribution, macrophages can be functionally polarized into M1 (proinflammatory) and M2 (alternatively activated) as well as regulatory cells in response to both exogenous infections and solid tumors as well as by systems biology approaches. PMID:22194670

  1. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

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    Afonso José Pereira Cortez

    2011-02-01

    Full Text Available BACKGROUND: Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. OBJECTIVES: To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. METHODS: A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. RESULTS: The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. CONCLUSION: Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not

  2. Autologous fat grafting for cosmetic enhancement of the perioral region.

    Science.gov (United States)

    Glasgold, Mark; Lam, Samuel M; Glasgold, Robert

    2007-11-01

    The role of volume loss in the progression of facial aging is widely accepted as an important cause. The aging appearance of the perioral region and lower face is significantly affected by this volume loss, which contributes to the development of labiomental folds, the loss of definition of the jawline, and worsening of skin texture, among other manifestations. Autologous fat transfer can effectively replace this lost volume and contribute to any facial rejuvenation plan. Fat can replace larger volumes than off-the-shelf fillers and provides a potentially permanent solution.

  3. Facial fat necrosis following autologous fat transfer and its management

    Directory of Open Access Journals (Sweden)

    Sweta Rai

    2014-01-01

    Full Text Available Autologous fat transfer (AFT is an increasingly popular cosmetic procedure practiced by dermatologic surgeons worldwide. As this is an office based procedure performed under local or tumescent anaesthesia with fat transferred within the same individual and limited associated down time its is considered relatively safe and risk free in the cosmetic surgery arena. We describe a case of AFT related fat necrosis causing significant facial dysmorphia and psychosocial distress. We also discuss the benefits and risks of AFT highlighting common causes of fat graft failure.

  4. LOCAL CORTICOSTEROID VS. AUTOLOGOUS BLOOD FOR PLANTAR FASCIITIS

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    Syam Sunder B

    2017-01-01

    Full Text Available BACKGROUND Plantar fasciitis is the most common cause of heel pain for which professional care is sought. Initially thought of as an inflammatory process, plantar fasciitis is a disorder of degenerative changes in the fascia and maybe more accurately termed plantar fasciosis. Traditional therapeutic efforts have been directed at decreasing the presumed inflammation. These treatments include icing, Nonsteroidal Anti-inflammatory Drugs (NSAIDs, rest and activity modification, corticosteroids, botulinum toxin type A, splinting, shoe modifications and orthosis. Other treatment techniques have been directed at resolving the degeneration caused by the disease process. In general, these techniques are designed to create an acute inflammatory reaction with the goal of restarting the healing process. These techniques include autologous blood injection, Platelet-Rich Plasma (PRP injection, nitroglycerin patches, Extracorporeal Shock Wave Therapy (ESWT and surgical procedures. Recently, research has focused on regenerative therapies with high expectations of success. The use of autologous growth factors is thought to heal through collagen regeneration and the stimulation of a well-ordered angiogenesis. These growth factors are administered in the form of autologous whole blood or Platelet-Rich Plasma (PRP. Platelets can be isolated using simple cell-separating systems. The degranulation of the alpha granules in the platelets releases many different growth factors that play a role in tissue regeneration processes. Platelet-derived growth factor, transforming growth factor-P, vascular-derived endothelial growth factor, epithelial growth factor, hepatocyte growth factor and insulin-like growth factor are examples of such growth factors. Injections with autologous growth factors are becoming common in clinical practice. The present study was an attempt to compare the efficacy of autologous blood injection in plantar fasciitis by comparing it with the local

  5. Autologous Fat Transfer: An Aesthetic and Functional Refinement for Parotidectomy

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    Pierre G. Vico

    2014-01-01

    Full Text Available Parotidectomy is a surgical procedure associated to functional (Frey’s syndrome as well as aesthetic (facial asymmetry complications that can be very disturbing for the patient. Several procedures have been described to primarily avoid or secondarily reconstruct the facial defect and treat the neurological iatrogenic syndrome. Autologous fat transfer was primarily used in 10 cases to avoid such complications. It is an easy technique widely used in cosmetic and reconstructive surgery. This technique gives very satisfying long-term results on the cosmetic as well as on the physiological point of view.

  6. Autologous 111In-oxine-labeled granulocytes in Yersinia infections

    International Nuclear Information System (INIS)

    Becker, W.; Boerner, W.; Fischbach, W.

    1985-01-01

    Autologous 111 In-oxine-labeled granulocytes have proved to be valuable for the localization of inflammatory bowel diseases, especially Crohn's disease and ulcerative colitis. Other rare inflammatory bowel diseases also yield positive 111 In scans. One case of Yersinia infection of the terminal ileum (Yersinia enterocolitica) showing an accumulation of 111 In-oxine-labeled granulocytes 0.5, 4, and 24 h after the reinjection of the labeled cells is described. The 4-day fecal excretion of 111 In-oxine granulocytes showed a slight inflammatory activity of the terminal ileum. One negative scan is reported in a cotrimoxazole-treated patient with Yersinia infection. (orig.)

  7. Pulmonary heart valve replacement using stabilized acellular xenogeneic scaffolds; effects of seeding with autologous stem cells

    Directory of Open Access Journals (Sweden)

    Harpa Marius Mihai

    2015-12-01

    Full Text Available Background: We hypothesized that an ideal heart valve replacement would be acellular valve root scaffolds seeded with autologous stem cells. To test this hypothesis, we prepared porcine acellular pulmonary valves, seeded them with autologous adipose derived stem cells (ADSCs and implanted them in sheep and compared them to acellular valves.

  8. Human macrophage responses to clinical isolates from the Mycobacterium tuberculosis complex discriminate between ancient and modern lineages.

    Directory of Open Access Journals (Sweden)

    Damien Portevin

    2011-03-01

    Full Text Available The aim of the present study was to determine whether there is a correlation between phylogenetic relationship and inflammatory response amongst a panel of clinical isolates representative of the global diversity of the human Mycobacterium tuberculosis Complex (MTBC. Measurement of cytokines from infected human peripheral blood monocyte-derived macrophages revealed a wide variation in the response to different strains. The same pattern of high or low response to individual strains was observed for different pro-inflammatory cytokines and chemokines, and was conserved across multiple human donors. Although each major phylogenetic lineage of MTBC included strains inducing a range of cytokine responses, we found that overall inflammatory phenotypes differed significantly across lineages. In particular, comparison of evolutionarily modern lineages demonstrated a significant skewing towards lower early inflammatory response. The differential response to ancient and modern lineages observed using GM-CSF derived macrophages was also observed in autologous monocyte-derived dendritic cells and murine bone marrow-derived macrophages, but not in human unfractionated peripheral blood mononuclear cells. We hypothesize that the reduced immune responses to modern lineages contribute to more rapid disease progression and transmission, which might be a selective advantage in the context of expanding human populations. In addition to the lineage effects, the large strain-to-strain variation in innate immune responses elicited by MTBC will need to be considered in tuberculosis vaccine development.

  9. HIV-1 Latency in Monocytes/Macrophages

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    Amit Kumar

    2014-04-01

    Full Text Available Human immunodeficiency virus type 1 (HIV-1 targets CD4+ T cells and cells of the monocyte/macrophage lineage. HIV pathogenesis is characterized by the depletion of T lymphocytes and by the presence of a population of cells in which latency has been established called the HIV-1 reservoir. Highly active antiretroviral therapy (HAART has significantly improved the life of HIV-1 infected patients. However, complete eradication of HIV-1 from infected individuals is not possible without targeting latent sources of infection. HIV-1 establishes latent infection in resting CD4+ T cells and findings indicate that latency can also be established in the cells of monocyte/macrophage lineage. Monocyte/macrophage lineage includes among others, monocytes, macrophages and brain resident macrophages. These cells are relatively more resistant to apoptosis induced by HIV-1, thus are important stable hideouts of the virus. Much effort has been made in the direction of eliminating HIV-1 resting CD4+ T-cell reservoirs. However, it is impossible to achieve a cure for HIV-1 without considering these neglected latent reservoirs, the cells of monocyte/macrophage lineage. In this review we will describe our current understanding of the mechanism of latency in monocyte/macrophage lineage and how such cells can be specifically eliminated from the infected host.

  10. The Many Alternative Faces of Macrophage Activation.

    Science.gov (United States)

    Hume, David A

    2015-01-01

    Monocytes and macrophages provide the first line of defense against pathogens. They also initiate acquired immunity by processing and presenting antigens and provide the downstream effector functions. Analysis of large gene expression datasets from multiple cells and tissues reveals sets of genes that are co-regulated with the transcription factors that regulate them. In macrophages, the gene clusters include lineage-specific genes, interferon-responsive genes, early inflammatory genes, and genes required for endocytosis and lysosome function. Macrophages enter tissues and alter their function to deal with a wide range of challenges related to development and organogenesis, tissue injury, malignancy, sterile, or pathogenic inflammatory stimuli. These stimuli alter the gene expression to produce "activated macrophages" that are better equipped to eliminate the cause of their influx and to restore homeostasis. Activation or polarization states of macrophages have been classified as "classical" and "alternative" or M1 and M2. These proposed states of cells are not supported by large-scale transcriptomic data, including macrophage-associated signatures from large cancer tissue datasets, where the supposed markers do not correlate with other. Individual macrophage cells differ markedly from each other, and change their functions in response to doses and combinations of agonists and time. The most studied macrophage activation response is the transcriptional cascade initiated by the TLR4 agonist lipopolysaccharide. This response is reviewed herein. The network topology is conserved across species, but genes within the transcriptional network evolve rapidly and differ between mouse and human. There is also considerable divergence in the sets of target genes between mouse strains, between individuals, and in other species such as pigs. The deluge of complex information related to macrophage activation can be accessed with new analytical tools and new databases that provide

  11. Autologous hematopoietic stem cells for refractory Crohn's disease.

    Science.gov (United States)

    DiNicola, C A; Zand, A; Hommes, D W

    2017-05-01

    Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.

  12. Subcutaneous autologous serum therapy in chronic spontaneous urticaria

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    Kiran Vasant Godse

    2017-01-01

    Full Text Available Background: There is a felt need for trying newer therapeutic modalities in patients with chronic spontaneous urticaria, especially in the subset of patients classified as non-responders to antihistamines. Autologous serum therapy is an upcoming modality of treatment, and we decided to study its efficacy by subcutaneous route. Aims: To evaluate the effectiveness of subcutaneous autologous serum therapy (AST in CSU. Methods: This was a single blind, placebo-controlled parallel group, randomized, controlled study. Twenty-four patients with CSU (11M: 13 F were given subcutaneous AST and seventeen patients (7 M: 10F patients were given subcutaneous injection normal saline (placebo, along with levocetirizine in an on-demand basis in both groups. Results: Urticaria activity score (UAS came down from 35.74 to 7 at the end of 9 weeks and the patients' requirement of antihistamines also reduced remarkably from 5.8 to 1.7 per week in the serum group. Sub-cutaneous saline group did not show statistically significant fall in UAS. Saline group showed UAS 32.8 at zero week to 22.1 at the end of 9 weeks. DLQI showed significant fall in serum group, from 14.26 to 4 at the end of 9 weeks. Conclusion: Subcutaneous autoserum therapy is effective in treatment of CSU.

  13. MR imaging of osteochondral grafts and autologous chondrocyte implantation

    Energy Technology Data Exchange (ETDEWEB)

    Trattnig, S. [Medical University of Vienna, MR Centre of Excellence, Department of Radiology, Vienna (Austria); University Hospital of Vienna, MR-Center, Department of Radiology, Vienna (Austria); Millington, S.A. [Medical University of Vienna, MR Centre of Excellence, Department of Radiology, Vienna (Austria); Medical University of Vienna, Department of Trauma Surgery, Center for Joints and Cartilage, Vienna (Austria); Szomolanyi, P. [Medical University of Vienna, MR Centre of Excellence, Department of Radiology, Vienna (Austria); Marlovits, S. [Medical University of Vienna, Department of Trauma Surgery, Center for Joints and Cartilage, Vienna (Austria)

    2007-01-15

    Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible. (orig.)

  14. Alteration of Skin Properties with Autologous Dermal Fibroblasts

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    Rajesh L. Thangapazham

    2014-05-01

    Full Text Available Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

  15. Autologous Bone Marrow Mononuclear Cells Intrathecal Transplantation in Chronic Stroke

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    Alok Sharma

    2014-01-01

    Full Text Available Cell therapy is being widely explored in the management of stroke and has demonstrated great potential. It has been shown to assist in the remodeling of the central nervous system by inducing neurorestorative effect through the process of angiogenesis, neurogenesis, and reduction of glial scar formation. In this study, the effect of intrathecal administration of autologous bone marrow mononuclear cells (BMMNCs is analyzed on the recovery process of patients with chronic stroke. 24 patients diagnosed with chronic stroke were administered cell therapy, followed by multidisciplinary neurorehabilitation. They were assessed on functional independence measure (FIM objectively, along with assessment of standing and walking balance, ambulation, and hand functions. Out of 24 patients, 12 improved in ambulation, 10 in hand functions, 6 in standing balance, and 9 in walking balance. Further factor analysis was done. Patients of the younger groups showed higher percentage of improvement in all the areas. Patients who underwent cell therapy within 2 years after the stroke showed better changes. Ischemic type of stroke had better recovery than the hemorrhagic stroke. This study demonstrates the potential of autologous BMMNCs intrathecal transplantation in improving the prognosis of functional recovery in chronic stage of stroke. Further clinical trials are recommended. This trial is registered with NCT02065778.

  16. Autologous Blood Injection and Wrist Immobilisation for Chronic Lateral Epicondylitis

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    Nicola Massy-Westropp

    2012-01-01

    Full Text Available Purpose. This study explored the effect of autologous blood injection (with ultrasound guidance to the elbows of patients who had radiologically assessed degeneration of the origin of extensor carpi radialis brevis and failed cortisone injection/s to the lateral epicondylitis. Methods. This prospective longitudinal series involved preinjection assessment of pain, grip strength, and function, using the patient-rated tennis elbow evaluation. Patients were injected with blood from the contralateral limb and then wore a customised wrist support for five days, after which they commenced a stretching, strengthening, and massage programme with an occupational therapist. These patients were assessed after six months and then finally between 18 months and five years after injection, using the patient-rated tennis elbow evaluation. Results. Thirty-eight of 40 patients completed the study, showing significant improvement in pain; the worst pain decreased by two to five points out of a 10-point visual analogue for pain. Self-perceived function improved by 11–25 points out of 100. Women showed significant increase in grip, but men did not. Conclusions. Autologous blood injection improved pain and function in a worker’s compensation cohort of patients with chronic lateral epicondylitis, who had not had relief with cortisone injection.

  17. Monocyte/macrophage-derived soluble CD163

    DEFF Research Database (Denmark)

    Andersen, Morten N; Abildgaard, Niels; Maniecki, Maciej B

    2014-01-01

    in bone marrow samples than in the matched blood samples, which indicate a localized production of sCD163 within the bone marrow microenvironment. CONCLUSIONS: Soluble CD163 was found to be a prognostic marker in patients with multiple myeloma. This may indicate that macrophages and/or monocytes have......OBJECTIVES: Macrophages play an important role in cancer by suppression of adaptive immunity and promotion of angiogenesis and metastasis. Tumor-associated macrophages strongly express the hemoglobin scavenger receptor CD163, which can also be found as a soluble protein in serum and other body...

  18. Dexamethasone targeted directly to macrophages induces macrophage niches that promote erythroid expansion

    DEFF Research Database (Denmark)

    Falchi, Mario; Varricchio, Lilian; Martelli, Fabrizio

    2015-01-01

    Cultures of human CD34(pos) cells stimulated with erythroid growth factors plus dexamethasone, a model for stress erythropoiesis, generate numerous erythroid cells plus a few macrophages (approx. 3%; 3:1 positive and negative for CD169). Interactions occurring between erythroblasts and macrophages...... in these cultures and the biological effects associated with these interactions were documented by live phase-contrast videomicroscopy. Macrophages expressed high motility interacting with hundreds/thousands of erythroblasts per hour. CD169(pos) macrophages established multiple rapid 'loose' interactions...... with proerythroblasts leading to formation of transient erythroblastic island-like structures. By contrast, CD169(neg) macrophages established 'tight' interactions with mature erythroblasts and phagocytosed these cells. 'Loose' interactions of CD169(pos) macrophages were associated with proerythroblast cytokinesis (the...

  19. Macrophage Polarization in Obesity and Type 2 Diabetes: Weighing Down our Understanding of Macrophage Function?

    Directory of Open Access Journals (Sweden)

    Michael James Kraakman

    2014-09-01

    Full Text Available Obesity and type 2 diabetes are now recognized as chronic pro-inflammatory diseases. In the last decade, the role of the macrophage in particular has become increasingly implicated in their pathogenesis. Abundant literature now establishes that monocytes get recruited to peripheral tissues (ie pancreas, liver and adipose tissue to become resident macrophages and contribute to local inflammation, development of insulin resistance or even pancreatic dysfunction. Furthermore, an accumulation of evidence has established an important role for macrophage polarisation in the development of metabolic diseases. The general view in obesity is that there is an imbalance in the ratio of M1/M2 macrophages, with M1 pro-inflammatory macrophages being enhanced compared with M2 anti-inflammatory macrophages being down-regulated, leading to chronic inflammation and the propagation of metabolic dysfunction. However, there is emerging evidence revealing a more complex scenario with the spectrum of macrophage states exceeding well beyond the M1/M2 binary classification and confused further by human and animal models exhibiting different macrophage profiles. In this review we will discuss the recent findings regarding macrophage polarization in obesity and type 2 diabetes.

  20. Intimal lining layer macrophages but not synovial sublining macrophages display an IL-10 polarized-like phenotype in chronic synovitis

    NARCIS (Netherlands)

    Ambarus, Carmen A.; Noordenbos, Troy; de Hair, Maria J. H.; Tak, Paul P.; Baeten, Dominique L. P.

    2012-01-01

    Introduction: Synovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets in this process remains largely unknown. The main in vitro polarized macrophage subsets are classically (M1) and alternatively (M2) activated macrophages,

  1. Macrophage Recognition of Crystals and Nanoparticles

    Science.gov (United States)

    Nakayama, Masafumi

    2018-01-01

    Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However, it is unlikely that macrophages have evolutionally acquired receptors specific for crystals or recently emerged nanoparticles. Several recent studies have reported that some crystal particles are negatively charged and are recognized by scavenger receptor family members in a charge-dependent manner. Alternatively, a model for receptor-independent phagocytosis of crystals has also been proposed. This review focuses on the mechanisms by which macrophages recognize crystals and nanoparticles. PMID:29434606

  2. Macrophage Recognition of Crystals and Nanoparticles

    Directory of Open Access Journals (Sweden)

    Masafumi Nakayama

    2018-01-01

    Full Text Available Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However, it is unlikely that macrophages have evolutionally acquired receptors specific for crystals or recently emerged nanoparticles. Several recent studies have reported that some crystal particles are negatively charged and are recognized by scavenger receptor family members in a charge-dependent manner. Alternatively, a model for receptor-independent phagocytosis of crystals has also been proposed. This review focuses on the mechanisms by which macrophages recognize crystals and nanoparticles.

  3. Macrophage Recognition of Crystals and Nanoparticles.

    Science.gov (United States)

    Nakayama, Masafumi

    2018-01-01

    Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However, it is unlikely that macrophages have evolutionally acquired receptors specific for crystals or recently emerged nanoparticles. Several recent studies have reported that some crystal particles are negatively charged and are recognized by scavenger receptor family members in a charge-dependent manner. Alternatively, a model for receptor-independent phagocytosis of crystals has also been proposed. This review focuses on the mechanisms by which macrophages recognize crystals and nanoparticles.

  4. Botanical polysaccharides: macrophage immunomodulation and therapeutic potential.

    Science.gov (United States)

    Schepetkin, Igor A; Quinn, Mark T

    2006-03-01

    Botanical polysaccharides exhibit a number of beneficial therapeutic properties, and it is thought that the mechanisms involved in these effects are due to the modulation of innate immunity and, more specifically, macrophage function. In this review, we summarize our current state of understanding of the macrophage modulatory effects of botanical polysaccharides isolated from a wide array of different species of flora, including higher plants, mushrooms, lichens and algae. Overall, the primary effect of botanical polysaccharides is to enhance and/or activate macrophage immune responses, leading to immunomodulation, anti-tumor activity, wound-healing and other therapeutic effects. Furthermore, botanical and microbial polysaccharides bind to common surface receptors and induce similar immunomodulatory responses in macrophages, suggesting that evolutionarily conserved polysaccharide structural features are shared between these organisms. Thus, the evaluation of botanical polysaccharides provides a unique opportunity for the discovery of novel therapeutic agents and adjuvants that exhibit beneficial immunomodulatory properties.

  5. Epigenetic Regulation of Monocyte and Macrophage Function

    NARCIS (Netherlands)

    Hoeksema, Marten A.; de Winther, Menno P. J.

    2016-01-01

    Monocytes and macrophages are key players in tissue homeostasis and immune responses. Epigenetic processes tightly regulate cellular functioning in health and disease. Recent Advances: Recent technical developments have allowed detailed characterizations of the transcriptional circuitry underlying

  6. Extracellular Vesicles Released from Mycobacterium tuberculosis-Infected Neutrophils Promote Macrophage Autophagy and Decrease Intracellular Mycobacterial Survival

    Science.gov (United States)

    Alvarez-Jiménez, Violeta D.; Leyva-Paredes, Kahiry; García-Martínez, Mariano; Vázquez-Flores, Luis; García-Paredes, Víctor Gabriel; Campillo-Navarro, Marcia; Romo-Cruz, Israel; Rosales-García, Víctor Hugo; Castañeda-Casimiro, Jessica; González-Pozos, Sirenia; Hernández, José Manuel; Wong-Baeza, Carlos; García-Pérez, Blanca Estela; Ortiz-Navarrete, Vianney; Estrada-Parra, Sergio; Serafín-López, Jeanet; Wong-Baeza, Isabel; Chacón-Salinas, Rommel; Estrada-García, Iris

    2018-01-01

    Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb). In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs) (100–1,000 nm in diameter) to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication. We previously demonstrated that human neutrophils infected in vitro with Mtb H37Rv release EVs (EV-TB), but the effect of these EVs on other cells relevant for the control of Mtb infection, such as macrophages, has not been completely analyzed. In this study, we characterized the EVs produced by non-stimulated human neutrophils (EV-NS), and the EVs produced by neutrophils stimulated with an activator (PMA), a peptide derived from bacterial proteins (fMLF) or Mtb, and observed that the four EVs differed in their size. Ligands for toll-like receptor (TLR) 2/6 were detected in EV-TB, and these EVs favored a modest increase in the expression of the co-stimulatory molecules CD80, a higher expression of CD86, and the production of higher amounts of TNF-α and IL-6, and of lower amounts of TGF-β, in autologous human macrophages, compared with the other EVs. EV-TB reduced the amount of intracellular Mtb in macrophages, and increased superoxide anion production in these cells. TLR2/6 ligation and superoxide anion production are known inducers of autophagy; accordingly, we found that EV-TB induced higher expression of the autophagy-related marker LC3-II in macrophages, and the co-localization of LC3-II with Mtb inside infected macrophages. The intracellular mycobacterial load increased when autophagy was inhibited with

  7. Extracellular Vesicles Released from Mycobacterium tuberculosis-Infected Neutrophils Promote Macrophage Autophagy and Decrease Intracellular Mycobacterial Survival

    Directory of Open Access Journals (Sweden)

    Violeta D. Alvarez-Jiménez

    2018-02-01

    Full Text Available Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb. In the lungs, macrophages and neutrophils are the first immune cells that have contact with the infecting mycobacteria. Neutrophils are phagocytic cells that kill microorganisms through several mechanisms, which include the lytic enzymes and antimicrobial peptides that are found in their lysosomes, and the production of reactive oxygen species. Neutrophils also release extracellular vesicles (EVs (100–1,000 nm in diameter to the extracellular milieu; these EVs consist of a lipid bilayer surrounding a hydrophilic core and participate in intercellular communication. We previously demonstrated that human neutrophils infected in vitro with Mtb H37Rv release EVs (EV-TB, but the effect of these EVs on other cells relevant for the control of Mtb infection, such as macrophages, has not been completely analyzed. In this study, we characterized the EVs produced by non-stimulated human neutrophils (EV-NS, and the EVs produced by neutrophils stimulated with an activator (PMA, a peptide derived from bacterial proteins (fMLF or Mtb, and observed that the four EVs differed in their size. Ligands for toll-like receptor (TLR 2/6 were detected in EV-TB, and these EVs favored a modest increase in the expression of the co-stimulatory molecules CD80, a higher expression of CD86, and the production of higher amounts of TNF-α and IL-6, and of lower amounts of TGF-β, in autologous human macrophages, compared with the other EVs. EV-TB reduced the amount of intracellular Mtb in macrophages, and increased superoxide anion production in these cells. TLR2/6 ligation and superoxide anion production are known inducers of autophagy; accordingly, we found that EV-TB induced higher expression of the autophagy-related marker LC3-II in macrophages, and the co-localization of LC3-II with Mtb inside infected macrophages. The intracellular mycobacterial load increased when autophagy was inhibited

  8. The Many Alternative Faces of Macrophage Activation

    Science.gov (United States)

    Hume, David A.

    2015-01-01

    Monocytes and macrophages provide the first line of defense against pathogens. They also initiate acquired immunity by processing and presenting antigens and provide the downstream effector functions. Analysis of large gene expression datasets from multiple cells and tissues reveals sets of genes that are co-regulated with the transcription factors that regulate them. In macrophages, the gene clusters include lineage-specific genes, interferon-responsive genes, early inflammatory genes, and genes required for endocytosis and lysosome function. Macrophages enter tissues and alter their function to deal with a wide range of challenges related to development and organogenesis, tissue injury, malignancy, sterile, or pathogenic inflammatory stimuli. These stimuli alter the gene expression to produce “activated macrophages” that are better equipped to eliminate the cause of their influx and to restore homeostasis. Activation or polarization states of macrophages have been classified as “classical” and “alternative” or M1 and M2. These proposed states of cells are not supported by large-scale transcriptomic data, including macrophage-associated signatures from large cancer tissue datasets, where the supposed markers do not correlate with other. Individual macrophage cells differ markedly from each other, and change their functions in response to doses and combinations of agonists and time. The most studied macrophage activation response is the transcriptional cascade initiated by the TLR4 agonist lipopolysaccharide. This response is reviewed herein. The network topology is conserved across species, but genes within the transcriptional network evolve rapidly and differ between mouse and human. There is also considerable divergence in the sets of target genes between mouse strains, between individuals, and in other species such as pigs. The deluge of complex information related to macrophage activation can be accessed with new analytical tools and new databases

  9. Macrophage Polarization in Metabolism and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-08-01

    Full Text Available BACKGROUND: Obesity is now recognized as the main cause of the worldwide epidemic of type 2 diabetes. Obesity-associated chronic inflammation is a contributing key factor for type 2 diabetes and cardiovascular disease. Numbers of studies have clearly demonstrated that the immune system and metabolism are highly integrated. CONTENT: Macrophages are an essential component of innate immunity and play a central role in inflammation and host defense. Moreover, these cells have homeostatic functions beyond defense, including tissue remodeling in ontogenesis and orchestration of metabolic functions. Diversity and plasticity are hallmarks of cells of the monocyte-macrophage lineage. In response to interferons (IFNs, toll-like receptor (TLR, or interleukin (IL-4/IL-13 signals, macrophages undergo M1 (classical or M2 (alternative activation. Progress has now been made in defining the signaling pathways, transcriptional networks, and epigenetic mechanisms underlying M1, M2 or M2-like polarized activation. SUMMARY: In response to various signals, macrophages may undergo classical M1 activation (stimulated by TLR ligands and IFN-γ or alternative M2 activation (stimulated by IL-4/IL-13; these states mirror the T helper (Th1–Th2 polarization of T cells. Pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicate in initiating and sustaining inflammation, meanwhile M2 or M2-like activated cells associated with resolution or smoldering chronic inflammation. Identification of the mechanisms and molecules that are associated with macrophage plasticity and polarized activation provides a basis for macrophage centered diagnostic and therapeutic strategies. KEYWORDS: obesity, adipose tissue, inflammation, macrophage polarization.

  10. Macrophage Recognition of Crystals and Nanoparticles

    OpenAIRE

    Nakayama, Masafumi

    2018-01-01

    Inhalation of exogenous crystals such as silica, asbestos, and carbon nanotubes can cause lung fibrosis and cancer. Endogenous crystals such as monosodium urate, cholesterol, and hydroxyapatite are associated with pathogenesis of gout, atherosclerosis, and osteoarthritis, respectively. These crystal-associated-inflammatory diseases are triggered by the macrophage NLRP3 inflammasome activation and cell death. Therefore, it is important to understand how macrophages recognize crystals. However,...

  11. Endometriosis, a disease of the macrophage

    OpenAIRE

    Capobianco, Annalisa; Rovere-Querini, Patrizia

    2013-01-01

    Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularized endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where ...

  12. Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

    Directory of Open Access Journals (Sweden)

    Paulo Cesar Fagundes Neves

    2013-09-01

    Full Text Available OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6-8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each: control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model.

  13. Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing.

    Science.gov (United States)

    Neves, Paulo César Fagundes; Abib, Simone de Campos Vieira; Neves, Rogério Fagundes; Pircchio, Oronzo; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Simões, Ricardo Santos; Moreira, Marcia Bento; Laurino, Cristiano Frota de Souza

    2013-09-01

    The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. A total of 128 male New Zealand albino rabbits, between 6-8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model.

  14. Macrophages in intestinal homeostasis and inflammation

    Science.gov (United States)

    Bain, Calum C; Mowat, Allan McI

    2014-01-01

    The intestine contains the largest pool of macrophages in the body which are essential for maintaining mucosal homeostasis in the face of the microbiota and the constant need for epithelial renewal but are also important components of protective immunity and are involved in the pathology of inflammatory bowel disease (IBD). However, defining the biological roles of intestinal macrophages has been impeded by problems in defining the phenotype and origins of different populations of myeloid cells in the mucosa. Here, we discuss how multiple parameters can be used in combination to discriminate between functionally distinct myeloid cells and discuss the roles of macrophages during homeostasis and how these may change when inflammation ensues. We also discuss the evidence that intestinal macrophages do not fit the current paradigm that tissue-resident macrophages are derived from embryonic precursors that self-renew in situ, but require constant replenishment by blood monocytes. We describe our recent work demonstrating that classical monocytes constantly enter the intestinal mucosa and how the environment dictates their subsequent fate. We believe that understanding the factors that drive intestinal macrophage development in the steady state and how these may change in response to pathogens or inflammation could provide important insights into the treatment of IBD. PMID:24942685

  15. Endometriosis, a disease of the macrophage

    Directory of Open Access Journals (Sweden)

    Annalisa eCapobianco

    2013-01-01

    Full Text Available Endometriosis, a common cause of pelvic pain and female infertility, depends on the growth of vascularised endometrial tissue at ectopic sites. Endometrial fragments reach the peritoneal cavity during the fertile years: local cues decide whether they yield endometriotic lesions. Macrophages are recruited at sites of hypoxia and tissue stress, where they clear cell debris and heme-iron and generate pro-life and pro-angiogenesis signals. Macrophages are abundant in endometriotic lesions, where are recruited and undergo alternative activation. In rodents macrophages are required for lesions to establish and to grow; bone-marrow derived Tie-2 expressing macrophages specifically contribute to lesions neovasculature, possibly because they concur to the recruitment of circulating endothelial progenitors, and sustain their survival and the integrity of the vessel wall. Macrophages sense cues (hypoxia, cell death, iron overload in the lesions and react delivering signals to restore the local homeostasis: their action represents a necessary, non-redundant step in the natural history of the disease. Endometriosis may be due to a misperception of macrophages about ectopic endometrial tissue. They perceive it as a wound, they activate programs leading to ectopic cell survival and tissue vascularization. Clearing this misperception is a critical area for the development of novel medical treatments of endometriosis, an urgent and unmet medical need.

  16. Macrophages and nerve fibres in peritoneal endometriosis.

    Science.gov (United States)

    Tran, Lu Vinh Phuc; Tokushige, Natsuko; Berbic, Marina; Markham, Robert; Fraser, Ian S

    2009-04-01

    Endometriosis is considered to be an inflammatory disease, and macrophages are the most numerous immune cells in endometriotic lesions. However, the mechanisms underlying the elevation of macrophages and their role in the pathogenesis and manifestations of endometriosis still remain unclear. The number of macrophages stained for CD68 in endometriotic lesions (n = 24) and in peritoneum distant from the lesions (n = 14) from women with endometriosis was compared with the number of macrophages in normal peritoneum from women without endometriosis (n = 18). Peritoneal lesions were also double-stained for CD68 and protein gene product 9.5 to study the relationship between macrophages and nerve fibres. The densities of macrophages in peritoneal endometriotic lesions and unaffected peritoneum from women with endometriosis were both significantly higher than that in normal peritoneum from women without endometriosis (P peritoneal lesions from women with endometriosis compared with normal peritoneum from women without endometriosis. These cells may well play roles in the growth and development of endometriotic lesions and in the generation of pain through interaction with nerve fibres.

  17. Autologous stem cell transplantation in the treatment of Hodgkin's disease

    Directory of Open Access Journals (Sweden)

    Tarabar Olivera

    2009-01-01

    Full Text Available Background/Aim. High-dose chemotherapy with autologous stem cell transplantacion (ASCT has shown to produce long-term disease-free survival in patients with chemotherapysensitive Hodgkin disease. The aim of the study was to evaluate efficacy of ASCT in the treatment of Hodgkin's disease. Methods. Between May 1997 and September 2008, 34 patients with Hodgkin's disease in median age of 25 (range 16-60 years, underwent ASCT. Autologous SCT were performed as consolidation therapy in one poor-risk patients with complete response (CR and in 10 patients in partial remission (PR after induction chemotherapy (32.5%, for chemosensitive relapse (CSR 1 and CSR 2 in 47% patients and in 20.5% patients with chemoresistant disease (CRD. All except one patient were in stage III/IV, extranodal site of disease had 24 patients and bulky disease had l0 patients. All the patients received a uniform preparatory regimen (BEAM. Results. An overall response was achieved in 30 of 32 evaluated patients, with 62.5% in CR and 31.25% in PR. After applying radiotherapy, two patients with PR after ASCT reached CR. Median follow-up was 15.5 months (range 3-133 months. The probability of overall survival (OS and progression-free survival (PFS at a 3-year period for all patients was 51.9 % and 48.9%, respectively. For 22 patients in CR after ASCT, a 3-year DFS was 66.5%. Estimates of 2.5-year survival were 14.3%, 61.9% and 100% for CRD, CSR and for patients with CR/PR, respectively (p < 0.01. However, when patients undergoing consolidation were analyzed separately from those in CSR, no significant difference in OS and PFS was observed according to the disease status at ASCT. In univariate analysis for OS, PFS i DFS, extranodal site of disease and disease bulk had no predictive value. Twelve patients died. The main cause of death was Hodgkin's disease. Transplant-related mortality was 3.1%. One patient with CRD developed secondary acute myeloid leukemia and died 28 months after the

  18. A prospective, randomized study of preoperative autologous donation for hip replacement surgery.

    Science.gov (United States)

    Billote, Dinna B; Glisson, Silas N; Green, David; Wixson, Richard L

    2002-08-01

    Preoperative autologous blood donation is commonly performed to meet potential perioperative transfusion needs and is a common practice prior to total hip arthroplasty. Using standardized transfusion guidelines, we prospectively analyzed the effectiveness of preoperative autologous donation as a method for decreasing allogeneic transfusion among patients undergoing unilateral primary total hip replacement who were eligible to donate autologous blood. Patients who were scheduled for primary total hip replacement surgery and who had a preoperative baseline hemoglobin level >or=120 g/L were randomized either to donate two units of blood (autologous donors) or not to donate any blood (nondonors). The donors and nondonors were compared with regard to demographic data, blood-loss volumes, hemoglobin measurements, and transfusion rates. Randomization continued until data were obtained from at least forty patients per treatment group. Of the ninety-six patients who completed the study, forty-two were autologous donors and fifty-four were nondonors. There were no significant differences between the donors and nondonors with regard to age, male:female ratio, estimated blood volume, baseline physical condition, or operative blood loss. The hemoglobin values at the time of enrollment (baseline), at the time of hospital discharge, and six weeks postoperatively were not significantly different between the two groups, although values at the time of admission (129 +/- 13 g/L versus 138 +/- 12 g/L) and in the recovery room (104 +/- 12 g/L versus 115 +/- 13 g/L) were significantly lower in the autologous donor group (p group required an allogeneic transfusion. Twenty-nine (69%) of the forty-two donors received an autologous transfusion. Thirty-four (41%) of eighty-two autologous units were wasted. At a charge of $379 per autologous unit, there was an additional cost of $758 for each patient in the donor group. Preoperative autologous donation provided no benefit for nonanemic

  19. Th1-like human T-cell clones recognizing Leishmania gp63 inhibit Leishmania major in human macrophages

    DEFF Research Database (Denmark)

    Kemp, M; Hey, A S; Bendtzen, K

    1994-01-01

    The major surface protease of Leishmania major, gp63, has been suggested as a vaccine candidate for cutaneous leishmaniasis. In this study gp63 was purified from L. major promastigotes. A panel of human T-cell clones recognizing this protein were generated from individuals who had previously had...... self-healing cutaneous leishmaniasis. The T-cell clones expressed CD4, and the alpha chain of the T-cell antigen receptor. GP63 reactive T-cell clones activated by antigen or by immobilized anti-CD3 antibody released relative large amounts of interferon-gamma and no or little interleukin-4, thereby...... resembling Th1 cells. Autologous mononuclear cells and Epstein-Barr virus-transformed B cell lines were equally efficient in presenting the antigen to the T cells. The gp63 reactive T cells induced resistance to infection in cultured human macrophages by L. major. The data confirm that human CD4+ T cells...

  20. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    International Nuclear Information System (INIS)

    Torpey, D.J. III.

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with 51 Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant

  1. Mobilization of hematopoietic progenitor cells for autologous transportation: consensus recommendations

    Directory of Open Access Journals (Sweden)

    Fernando Barroso Duarte

    Full Text Available SUMMARY Selected patients with certain hematological malignancies and solid tumors have the potential to achieve long-term survival with autologous hematopoietic progenitor cell transplant. The collection of these cells in peripheral blood avoids multiple bone marrow aspirations, results in faster engraftment and allows treatment of patients with infection, fibrosis, or bone marrow hypocellularity. However, for the procedure to be successful, it is essential to mobilize a sufficient number of progenitor cells from the bone marrow into the blood circulation. Therefore, a group of Brazilian experts met in order to develop recommendations for mobilization strategies adapted to the reality of the Brazilian national health system, which could help minimize the risk of failure, reduce toxicity and improve the allocation of financial resources.

  2. Surgical management and autologous intestinal reconstruction in short bowel syndrome.

    Science.gov (United States)

    Hommel, Matthijs J; van Baren, Robertine; Haveman, Jan Willem

    2016-04-01

    Short bowel syndrome (SBS) is a serious condition with considerable morbidity and mortality. When treatment with parenteral nutrition fails and life-threatening complications occur, autologous intestinal reconstruction (AIR) should be considered before intestinal transplantation (ITx). Single or combined ITx should be reserved for patients with severe liver disease and as last resort in the treatment of SBS. Longitudinal intestinal lengthening and tailoring (LILT) has proven its value in AIR, but its availability depends on the expertise of the surgeons. Serial transverse enteroplasty (STEP) has similar success rates as LILT and fewer patients progress to ITx. STEP is also applicable at small bowel dilatation in ultra-short bowel syndrome. The scope may be widened when duodenal dilatation can be treated as well. Spiral intestinal lengthening and tailoring (SILT) is a promising alternative. More research is needed to confirm these findings. Therefore we suggest an international data registry for all intestinal lengthening procedures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Transcriptomic biomarkers of altered erythropoiesis to detect autologous blood transfusion.

    Science.gov (United States)

    Salamin, Olivier; Mignot, Jonathan; Kuuranne, Tiia; Saugy, Martial; Leuenberger, Nicolas

    2018-03-01

    Autologous blood transfusion is a powerful means of improving performance and remains one of the most challenging methods to detect. Recent investigations have identified 3 candidate reticulocytes genes whose expression was significantly influenced by blood transfusion. Using quantitative reverse transcription polymerase chain reaction as an alternative quantitative method, the present study supports that delta-aminolevulinate synthase 2 (ALAS2), carbonic anhydrase (CA1), and solute carrier family 4 member 1 (SLC4A1) genes are down-regulated post-transfusion. The expression of these genes exhibited stronger correlation with immature reticulocyte fraction than with reticulocytes percentage. Moreover, the repression of reticulocytes' gene expression was more pronounced than the diminution of immature reticulocyte fraction and reticulocyte percentage following blood transfusion. It suggests that the 3 candidate genes are reliable predictors of bone marrow's response to blood transfusion and that they represent potential biomarkers for the detection of this method prohibited in sports. Copyright © 2017 John Wiley & Sons, Ltd.

  4. Immunisation of colorectal cancer patients with autologous tumour cells

    DEFF Research Database (Denmark)

    Diederichsen, Axel Cosmus Pyndt; Stenholm, A C; Kronborg, O

    1998-01-01

    . There was an inverse relation between survival and HLA class II expression. This highlights an essential problem, in the absence of CD80 expression the expression of HLA class II may induce anergy. In future attempts to develop improved vaccines this problem should be addressed.......Patients with colorectal cancer were entered into a clinical phase I trial of immunotherapy with an autologous tumour cell/bacillus Calmette-Guerin (BCG) vaccine. We attempted to describe the possible effects and side effects of the immunisation, and further to investigate whether expression...... of immune-response-related surface molecules on the tumour cells in the vaccine correlated with survival. The first and second vaccine comprised of 107 irradiated tumour cells mixed with BCG, the third of irradiated tumour cells only. Thirty-nine patients were considered, but only 6 patients fulfilled...

  5. MR imaging of autologous chondrocyte implantation of the knee

    Energy Technology Data Exchange (ETDEWEB)

    James, S.L.J.; Connell, D.A.; Saifuddin, A.; Skinner, J.A.; Briggs, T.W.R. [RNOH Stanmore, Department of Radiology, Stanmore, Middlesex (United Kingdom)

    2006-05-15

    Autologous chondrocyte implantation (ACI) is a surgical technique that is increasingly being used in the treatment of full-thickness defects of articular cartilage in the knee. It involves the arthroscopic harvesting and in vitro culture of chondrocytes that are subsequently implanted into a previously identified chondral defect. The aim is to produce a repair tissue that closely resembles hyaline articular cartilage that gradually becomes incorporated, restoring joint congruity. Over the long term, it is hoped that this will prevent the progression of full-thickness articular cartilage defects to osteoarthritis. This article reviews the indications and operative procedure performed in ACI. Magnetic resonance imaging (MRI) sequences that provide optimal visualization of articular cartilage in the post-operative period are discussed. Normal appearances of ACI on MRI are presented along with common complications that are encountered with this technique. (orig.)

  6. Radiation-induced autologous in situ tumor vaccines

    International Nuclear Information System (INIS)

    Guha, Chandan

    2014-01-01

    Radiation therapy (RT) has been used as a definitive treatment for many solid tumors. While tumoricidal properties of RT are instrumental for standard clinical application, irradiated tumors can potentially serve as a source of tumor antigens in vivo, where dying tumor cells would release tumor antigens and danger signals and serve as autologous in situ tumor vaccines. Using murine tumor models of prostate, metastatic lung cancer and melanoma, we have demonstrated evidence of radiation-enhanced tumor-specific immune response that resulted in improved primary tumor control and reduction in systemic metastasis and cure. We will discuss the immunogenic properties of RT and determine how immunotherapeutic approaches can synergize with RT in boosting immune cells cell function. (author)

  7. Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients

    Directory of Open Access Journals (Sweden)

    Zabel Peter

    2005-07-01

    Full Text Available Abstract Backround Cigarette smoke exposure including biologically active lipopolysaccharide (LPS in the particulate phase of cigarette smoke induces activation of alveolar macrophages (AM and alveolar epithelial cells leading to production of inflammatory mediators. This represents a crucial mechanism in the pathogenesis of chronic obstructive pulmonary disease (COPD. Respiratory pathogens are a major cause of exacerbations leading to recurrent cycles of injury and repair. The interaction between pathogen-associated molecular patterns and the host is mediated by pattern recognition receptors (PRR's. In the present study we characterized the expression of Toll-like receptor (TLR- 2, TLR4 and CD14 on human AM compared to autologous monocytes obtained from patients with COPD, healthy smokers and non-smokers. Methods The study population consisted of 14 COPD patients without evidence for acute exacerbation, 10 healthy smokers and 17 healthy non-smokers stratified according to age. The expression of TLR2, TLR4 and CD14 surface molecules on human AM compared to autologous monocytes was assessed ex vivo using FACS analysis. In situ hybridization was performed on bronchoalveolar lavage (BAL cells by application of the new developed HOPE-fixative. Results The expression of TLR2, TLR4 and CD14 on AM from COPD patients, smokers and non-smokers was reduced as compared to autologous monocytes. Comparing AM we detected a reduced expression of TLR2 in COPD patients and smokers. In addition TLR2 mRNA and protein expression was increased after LPS stimulation on non-smokers AM in contrast to smokers and COPD patients. Conclusion Our data suggest a smoke related change in the phenotype of AM's and the cellular response to microbial stimulation which may be associated with impairment of host defenses in the lower respiratory tract.

  8. Randomized phase II trial of autologous dendritic cell vaccines versus autologous tumor cell vaccines in metastatic melanoma: 5-year follow up and additional analyses.

    Science.gov (United States)

    Dillman, Robert O; Cornforth, Andrew N; Nistor, Gabriel I; McClay, Edward F; Amatruda, Thomas T; Depriest, Carol

    2018-03-06

    Despite improved survival following checkpoint inhibitors, there is still a potential role for anti-cancer therapeutic vaccines. Because of biological heterogeneity and neoantigens resulting from each patient's mutanome, autologous tumor may be the best source of tumor-associated antigens (TAA) for vaccines. Ex vivo loading of autologous dendritic cells with TAA may be associated with superior clinical outcome compared to injecting irradiated autologous tumor cells. We conducted a randomized phase II trial to compare autologous tumor cell vaccines (TCV) and autologous dendritic cell vaccines (DCV) loaded with autologous TAA. Short-term autologous tumor cell lines were established from metastatic tumor. Vaccines were admixed with 500 micrograms of GM-CSF and injected weekly for 3 weeks, then at weeks 8, 12,16, 20, and 24. The primary endpoint was overall survival. Secondary objectives were identification of adverse events, and results of delayed type hypersensitivity (DTH) reactions to intradermal tumor cell injections. Forty-two patients were randomized. All were followed from randomization until death or for five years; none were lost to follow-up. DCV was associated with longer survival: median 43.4 versus 20.5 months (95% CI, 18.6 to > 60 versus 9.3 to 32.3 months) and a 70% reduction in the risk of death (hazard ratio = 0.304, p = 0.0053, 95% CI, 0.131 to 0.702). Tumor DTH reactions were neither prognostic nor predictive. The most common treatment-related adverse events were mild to moderate local injection site reactions and flu-like symptoms; but grade 2 treatment-related adverse events were more frequent with TCV. Serum marker analyses at week-0 and week-4 showed that serum markers were similar at baseline in each arm, but differed after vaccination. This is the only human clinical trial comparing DCV and TCV as platforms for autologous TAA presentation. DCV was associated with minimal toxicity and long-term survival in patients with metastatic

  9. Human induced pluripotent stem cells on autologous feeders.

    Directory of Open Access Journals (Sweden)

    Kazutoshi Takahashi

    Full Text Available BACKGROUND: For therapeutic usage of induced Pluripotent Stem (iPS cells, to accomplish xeno-free culture is critical. Previous reports have shown that human embryonic stem (ES cells can be maintained in feeder-free condition. However, absence of feeder cells can be a hostile environment for pluripotent cells and often results in karyotype abnormalities. Instead of animal feeders, human fibroblasts can be used as feeder cells of human ES cells. However, one still has to be concerned about the existence of unidentified pathogens, such as viruses and prions in these non-autologous feeders. METHODOLOGY/PRINCIPAL FINDINGS: This report demonstrates that human induced Pluripotent Stem (iPS cells can be established and maintained on isogenic parental feeder cells. We tested four independent human skin fibroblasts for the potential to maintain self-renewal of iPS cells. All the fibroblasts tested, as well as their conditioned medium, were capable of maintaining the undifferentiated state and normal karyotypes of iPS cells. Furthermore, human iPS cells can be generated on isogenic parental fibroblasts as feeders. These iPS cells carried on proliferation over 19 passages with undifferentiated morphologies. They expressed undifferentiated pluripotent cell markers, and could differentiate into all three germ layers via embryoid body and teratoma formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that autologous fibroblasts can be not only a source for iPS cells but also be feeder layers. Our results provide a possibility to solve the dilemma by using isogenic fibroblasts as feeder layers of iPS cells. This is an important step toward the establishment of clinical grade iPS cells.

  10. DMPD: Shaping of monocyte and macrophage function by adenosine receptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17056121 Shaping of monocyte and macrophage function by adenosine receptors. Hasko ...G, Pacher P, Deitch EA, Vizi ES. Pharmacol Ther. 2007 Feb;113(2):264-75. Epub 2006 Sep 14. (.png) (.svg) (.html) (.csml) Show Shapi...ng of monocyte and macrophage function by adenosine receptors. PubmedID 17056121 Title Shapi

  11. DMPD: The actions of bacterial DNA on murine macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534106 The actions of bacterial DNA on murine macrophages. Sester DP, Stacey KJ, ...Sweet MJ, Beasley SJ, Cronau SL, Hume DA. J Leukoc Biol. 1999 Oct;66(4):542-8. (.png) (.svg) (.html) (.csml) Show The... actions of bacterial DNA on murine macrophages. PubmedID 10534106 Title The actions of bacterial D

  12. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  13. BMP pathway regulation of and by macrophages.

    Directory of Open Access Journals (Sweden)

    Megha Talati

    Full Text Available Pulmonary arterial hypertension (PAH is a disease of progressively increasing pulmonary vascular resistance, associated with mutations of the type 2 receptor for the BMP pathway, BMPR2. The canonical signaling pathway for BMPR2 is through the SMAD family of transcription factors. BMPR2 is expressed in every cell type, but the impact of BMPR2 mutations affecting SMAD signaling, such as Bmpr2delx4+, had only previously been investigated in smooth muscle and endothelium. In the present study, we created a mouse with universal doxycycline-inducible expression of Bmpr2delx4+ in order to determine if broader expression had an impact relevant to the development of PAH. We found that the most obvious phenotype was a dramatic, but patchy, increase in pulmonary inflammation. We crossed these double transgenic mice onto an NF-κB reporter strain, and by luciferase assays on live mice, individual organs and isolated macrophages, we narrowed down the origin of the inflammatory phenotype to constitutive activation of tissue macrophages. Study of bone marrow-derived macrophages from mutant and wild-type mice suggested a baseline difference in differentiation state in Bmpr2 mutants. When activated with LPS, both mutant and wild-type macrophages secrete BMP pathway inhibitors sufficient to suppress BMP pathway activity in smooth muscle cells (SMC treated with conditioned media. Functionally, co-culture with macrophages results in a BMP signaling-dependent increase in scratch closure in cultured SMC. We conclude that SMAD signaling through BMP is responsible, in part, for preventing macrophage activation in both live animals and in cells in culture, and that activated macrophages secrete BMP inhibitors in sufficient quantity to cause paracrine effect on vascular smooth muscle.

  14. A macrophage activation switch (MAcS)-index for assessment of monocyte/macrophage activation

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Lauridsen, Mette; Knudsen, Troels Bygum

    2008-01-01

    BACKGROUND: The monocyte/macrophage system plays important roles in host defense, regulation of immune responses, tissue repair, neovascularization, and inflammation. These diverse roles are performed by specific subpopulations of macrophages that are differently activated by surrounding stimuli...... is expressed exclusively on monocytes and macrophages, and its expression is strongly induced by anti-inflammatory stimuli like IL10 and glucocorticoid, making CD163 an ideal M2 macrophage marker (2). Furthermore a soluble variant of CD163 (sCD163) is shed from the cell surface to plasma by protease mediated...... for the resolution of inflammation. Clin Exp Immunol. 2005 Dec;142(3):481-9. 2. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M. The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol. 2004 Dec;25(12):677-86. 3. Weaver LK, Hintz-Goldstein KA, Pioli PA, Wardwell...

  15. Use of autologous platelet - Rich plasma in the treatment of intrabony defects

    Directory of Open Access Journals (Sweden)

    Sharath K Shetty

    2009-01-01

    Treatment of intrabony defects by autologous PRP gel alone caused significant soft tissue clinical improvement as well as hard tissue defect fill as evidenced by SSD view in spiral computed tomography.

  16. Local administration of autologous platelet-rich plasma in a female patient with skin ulcer defect

    Directory of Open Access Journals (Sweden)

    S M Noskov

    2011-01-01

    Full Text Available The paper describes a clinical observation of the efficiency of local therapy with autologous platelet-rich plasma for .skin ulcer defect in a female with chronic lymphocytic leukemia

  17. Rapid deterioration of preexisting renal insufficiency after autologous mesenchymal stem cell therapy

    Directory of Open Access Journals (Sweden)

    Jun-Seop Kim

    2017-06-01

    Full Text Available Administration of autologous mesenchymal stem cells (MSCs has been shown to improve renal function and histological findings in acute kidney injury (AKI models. However, its effects in chronic kidney disease (CKD are unclear, particularly in the clinical setting. Here, we report our experience with a CKD patient who was treated by intravenous infusion of autologous MSCs derived from adipose tissue in an unknown clinic outside of Korea. The renal function of the patient had been stable for several years before MSC administration. One week after the autologous MSC infusion, the preexisting renal insufficiency was rapidly aggravated without any other evidence of AKI. Hemodialysis was started 3 months after MSC administration. Renal biopsy findings at dialysis showed severe interstitial fibrosis and inflammatory cell infiltration, with a few cells expressing CD34 and CD117, 2 surface markers of stem cells. This case highlights the potential nephrotoxicity of autologous MSC therapy in CKD patients.

  18. Comparison of immune reconstitution after allogeneic vs. autologous stem cell transplantation in 182 pediatric recipients

    Directory of Open Access Journals (Sweden)

    V. Wiegering

    2017-03-01

    Conclusion: Children undergoing a HSCT show a different pattern of immune reconstitution in the allogeneic and autologous setting. This might influence the outcome and should affect the clinical handling of infectious prophylaxis and re-vaccinations.

  19. Ultrasound Diagnosis and Treatment of Breast Lumps after Breast Augmentation with Autologous Fat Grafting

    Directory of Open Access Journals (Sweden)

    Masaaki Shida, MD, PhD

    2017-12-01

    Conclusions:. The appropriate treatment for breast lumps after breast augmentation with autologous fat grafting must be selected according to the nature of the lumps. Ultrasound is essential for diagnosing the breast lump type and determining the best treatment.

  20. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Directory of Open Access Journals (Sweden)

    Mohssen Hakimi

    Full Text Available One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC. The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group. In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG, whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  1. The Efficacy and Safety of Autologous Transfusion in Unilateral Total Knee Arthroplasty

    OpenAIRE

    Yoo, Moon-Jib; Park, Hee-Gon; Ryu, Jee-Won; Kim, Jeong-Sang

    2015-01-01

    Purpose Although allogeneic blood transfusion is the most common method of transfusion in total knee arthroplasty (TKA), there are reports showing significant decrease in the amount of allogeneic transfusion and incidence of side effects after combined use of autologous transfusion. The purpose of this study is to investigate the efficacy of using an autologous transfusion device in TKA. Materials and Methods Patients who underwent TKA at our institution from January 2003 to January 2014 were...

  2. Comparative analysis of autologous blood transfusion and allogeneic blood transfusion in surgical patients

    OpenAIRE

    Long, Miao-Yun; Liu, Zhong-Han; Zhu, Jian-Guang

    2014-01-01

    Objective: To investigate application effects of autologous blood transfusion and allogeneic blood transfusion in surgically treated patients receiving spine surgery, abdomen surgery and ectopic pregnancy surgery. Methods: 130 patients who would undergo selective operations were divided into autologous transfusion group and allogeneic transfusion group. Both groups received the same anesthesia, and there was no significant difference in transfusion volume or fluid infusion volume. Results: Th...

  3. The composite of bone marrow concentrate and PRP as an alternative to autologous bone grafting.

    Science.gov (United States)

    Hakimi, Mohssen; Grassmann, Jan-Peter; Betsch, Marcel; Schneppendahl, Johannes; Gehrmann, Sebastian; Hakimi, Ahmad-Reza; Kröpil, Patric; Sager, Martin; Herten, Monika; Wild, Michael; Windolf, Joachim; Jungbluth, Pascal

    2014-01-01

    One possible alternative to the application of autologous bone grafts represents the use of autologous bone marrow concentrate (BMC). The purpose of our study was to evaluate the potency of autologous platelet-rich plasma (PRP) in combination with BMC. In 32 mini-pigs a metaphyseal critical-size defect was surgically created at the proximal tibia. The animals were allocated to four treatment groups of eight animals each (1. BMC+CPG group, 2. BMC+CPG+PRP group, 3. autograft group, 4. CPG group). In the BMC+CPG group the defect was filled with autologous BMC in combination with calcium phosphate granules (CPG), whereas in the BMC+CPG+PRP group the defect was filled with the composite of autologous BMC, CPG and autologous PRP. In the autograft group the defect was filled with autologous cancellous graft, whereas in the CPG group the defect was filled with CPG solely. After 6 weeks radiological and histomorphometrical analysis showed significantly more new bone formation in the BMC+CPG+PRP group compared to the BMC+CPG group and the CPG group. There were no significant differences between the BMC+CPG+PRP group and the autograft group. In the PRP platelets were enriched significantly about 4.7-fold compared to native blood. In BMC the count of mononuclear cells increased significantly (3.5-fold) compared to the bone marrow aspirate. This study demonstrates that the composite of BMC+CPG+PRP leads to a significantly higher bone regeneration of critical-size defects at the proximal tibia in mini-pigs than the use of BMC+CPG without PRP. Furthermore, within the limits of the present study the composite BMC+CPG+PRP represents a comparable alternative to autologous bone grafting.

  4. Latissimus Dorsi and Immediate Fat Transfer (LIFT for Complete Autologous Breast Reconstruction

    Directory of Open Access Journals (Sweden)

    James M. Economides, MD

    2018-01-01

    Conclusion:. Autologous augmentation of the LD flap with lipotransfer has been used to avoid placement of an implant. We improve the technique by performing lipotransfer during index reconstruction. Furthermore, we perform lipotransfer prior to disorigination of the LD muscle to minimize trauma to the flap and increase the efficiency of fat grafting. Our experience demonstrates that this technique is a viable autologous alternative to microsurgical breast reconstruction.

  5. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    Science.gov (United States)

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. Treatment of osteonecrosis of the femoral head using autologous cultured osteoblasts: a case report

    Directory of Open Access Journals (Sweden)

    Kim Seok-Jung

    2008-02-01

    Full Text Available Abstract Introduction Osteonecrosis of the femoral head is a progressive disease that leads to femoral head collapse and osteoarthritis. Our goal in treating osteonecrosis is to preserve, not to replace, the femoral head. Case presentation We present the case of a patient with bilateral osteonecrosis of the femoral head treated with autologous cultured osteoblast injection. Conclusion Although our experience is limited to one patient, autologous cultured osteoblast transplantation appears to be effective for treating the osteonecrosis of femoral head.

  7. Autologous bone graft versus demineralized bone matrix in internal fixation of ununited long bones

    OpenAIRE

    Rubenbauer Bianka; Löffler Thomas; Zaspel Johannes; Wittmann Alexandra; Pieske Oliver; Trentzsch Heiko; Piltz Stefan

    2009-01-01

    Abstract Background Non-unions are severe complications in orthopaedic trauma care and occur in 10% of all fractures. The golden standard for the treatment of ununited fractures includes open reduction and internal fixation (ORIF) as well as augmentation with autologous-bone-grafting. However, there is morbidity associated with the bone-graft donor site and some patients offer limited quantity or quality of autologous-bone graft material. Since allogene bone-grafts are introduced on the marke...

  8. Current developments in the tissue engineering of autologous heart valves: moving towards clinical use.

    Science.gov (United States)

    Apte, Sameer S; Paul, Arghya; Prakash, Satya; Shum-Tim, Dominique

    2011-01-01

    The use of tissue-engineering methods to create autologous heart valve constructs has the potential to overcome the fundamental drawbacks of more traditional valve prostheses. Traditional mechanical valves, while durable, increase the risk for endocarditis and thrombogenesis, and require the recipient to continue lifelong anticoagulant therapy. Homograft or xenograft heart valve prostheses are associated with immune reaction and progressive deterioration with limited durability. Most importantly, neither option is capable of growth and remodeling in vivo and both options place the patient at risk for valve-related complications and reoperation. These shortcomings have prompted the application of tissue-engineering techniques to create fully autologous heart valve replacements. Future clinically efficacious tissue-engineered autologous valves should be nonthrombogenic, biocompatible, capable of growth and remodeling in vivo, implantable with current surgical techniques, hemodynamically perfect, durable for the patient's life and most importantly, significantly improve quality of life for the patient. In order to meet these expectations, the nature of the ideal biochemical milieu for conditioning an autologous heart valve will need to be elucidated. In addition, standardized criteria by which to quantitatively evaluate a tissue-engineered heart valve, as well as noninvasive analytical techniques for use in long-term animal models, will be required. This article highlights the advances, challenges and future clinical prospects in the field of tissue engineering of autologous heart valves, focusing on progress made by studies that have investigated a fully autologous, tissue-engineered pulmonary valve replacement in vivo.

  9. Easy-to-prepare autologous platelet-rich plasma in the treatment of refractory corneal ulcers.

    Science.gov (United States)

    Wu, Tzu En; Chen, Chiung Ju; Hu, Chao-Chien; Cheng, Cheng-Kuo

    2015-01-01

    As platelets are rich in growth factors for tissue regeneration, autologous platelet-rich plasma (PRP) has been used to treat some refractory corneal defects. Although PRP is effective, the cost of its preparation is very high. This article presents three cases of refractory corneal ulcer under the prescription of autologous PRP. The autologous PRP used in these cases was easily prepared in the blood bank laboratory. In this paper, we collected three patients with refractory corneal ulcer who were unresponsive to conventional treatment. The patients presented with neurotrophic ulcer, exposure corneal ulcer, and limbal deciency with corneal ulcer after hepatitic keratitis. Although we easily prepared autologous PRP eye drops using simple laboratory centrifugation, this preparation still had a clinical effect on corneal defect. The mean intervention time was 24 ± 6.9 days. The case with exposure corneal ulcer had significant wound healing and the other two cases felt subjective symptom relief. There were some clinical improvements of refractory corneal ulcers in our three cases. We present the clinical results of three cases and report an easy procedure for the preparation of autologous PRP. Autologous PRP prepared simply in the laboratory, it may be an alternative option for treating refractory corneal ulcer.

  10. Ontogeny and Polarization of Macrophages in Inflammation: Blood monocytes versus tissue macrophages.

    Directory of Open Access Journals (Sweden)

    Adwitia eDey

    2015-01-01

    Full Text Available The explosion of new information in recent years on the origin of macrophages in the steady-state and in the context of inflammation has opened up numerous new avenues of investigation and possibilities for therapeutic intervention. In contrast to the classical model of macrophage development, it is clear that tissue-resident macrophages can develop from yolk sac-derived erythromyeloid progenitors, fetal liver progenitors and bone marrow-derived monocytes. Under both homeostatic conditions and in response to pathophysiological insult, the contribution of these distinct sources of macrophages varies significantly between tissues. Furthermore, while all of these populations of macrophages appear to be capable of adopting the polarized M1/M2 phenotypes, their respective contribution to inflammation, resolution of inflammation and tissue repair remains poorly understood and is likely to be tissue- and disease-dependent. A better understanding of the ontology and polarization capacity of macrophages in homeostasis and disease will be essential for the development of novel therapies that target the inherent plasticity of macrophages in the treatment of acute and chronic inflammatory disease.

  11. Biodegradation of carbon nanohorns in macrophage cells

    Science.gov (United States)

    Zhang, Minfang; Yang, Mei; Bussy, Cyrill; Iijima, Sumio; Kostarelos, Kostas; Yudasaka, Masako

    2015-02-01

    With the rapid developments in the medical applications of carbon nanomaterials such as carbon nanohorns (CNHs), carbon nanotubes, and graphene based nanomaterials, understanding the long-term fate, health impact, excretion, and degradation of these materials has become crucial. Herein, the in vitro biodegradation of CNHs was determined using a non-cellular enzymatic oxidation method and two types of macrophage cell lines. Approximately 60% of the CNHs was degraded within 24 h in a phosphate buffer solution containing myeloperoxidase. Furthermore, approximately 30% of the CNHs was degraded by both RAW 264.7 and THP-1 macrophage cells within 9 days. Inflammation markers such as pro-inflammatory cytokines interleukin 6 and tumor necrosis factor α were not induced by exposure to CNHs. However, reactive oxygen species were generated by the macrophage cells after uptake of CNHs, suggesting that these species were actively involved in the degradation of the nanomaterials rather than in an inflammatory pathway induction.With the rapid developments in the medical applications of carbon nanomaterials such as carbon nanohorns (CNHs), carbon nanotubes, and graphene based nanomaterials, understanding the long-term fate, health impact, excretion, and degradation of these materials has become crucial. Herein, the in vitro biodegradation of CNHs was determined using a non-cellular enzymatic oxidation method and two types of macrophage cell lines. Approximately 60% of the CNHs was degraded within 24 h in a phosphate buffer solution containing myeloperoxidase. Furthermore, approximately 30% of the CNHs was degraded by both RAW 264.7 and THP-1 macrophage cells within 9 days. Inflammation markers such as pro-inflammatory cytokines interleukin 6 and tumor necrosis factor α were not induced by exposure to CNHs. However, reactive oxygen species were generated by the macrophage cells after uptake of CNHs, suggesting that these species were actively involved in the degradation of the

  12. Concurrent administration of high-dose rituximab before and after autologous stem-cell transplantation for relapsed aggressive B-cell non-Hodgkin's lymphomas.

    Science.gov (United States)

    Khouri, Issa F; Saliba, Rima M; Hosing, Chitra; Okoroji, Grace-Julia; Acholonu, Sandra; Anderlini, Paolo; Couriel, Daniel; De Lima, Marcos; Donato, Michele L; Fayad, Luis; Giralt, Segio; Jones, Roy; Korbling, Martin; Maadani, Farzaneh; Manning, John T; Pro, Barbara; Shpall, Elizabeth; Younes, Anas; McLaughlin, Peter; Champlin, Richard E

    2005-04-01

    We investigated the efficacy and safety of administering high-dose rituximab (HD-R) in combination with high-dose carmustine, cytarabine, etoposide, and melphalan chemotherapy and autologous stem-cell transplantation (SCT) in patients with recurrent B-cell aggressive non-Hodgkin's lymphoma (NHL). Sixty-seven consecutive patients were treated. Rituximab was administered during stem-cell mobilization (1 day before chemotherapy at 375 mg/m(2) and 7 days after chemotherapy at 1,000 mg/m(2)), together with granulocyte colony-stimulating factor 10 mug/kg and granulocyte-macrophage colony-stimulating factor 250 microg/m(2) administered subcutaneously daily. HD-R of 1,000 mg/m(2) was administered again days 1 and 8 after transplantation. The results of this treatment were retrospectively compared with those of a historical control group receiving the same preparative regimen without rituximab. With a median follow-up time for the study group of 20 months, the overall survival rate at 2-years was 80% (95% CI, 65% to 89%) for the study group and 53% (95% CI, 34% to 69%) for the control group (P = .002). Disease-free survival was 67% (95% CI, 51% to 79%) for the study group and 43% (95% CI, 26% to 60%) for the control group (P = .004). The median time to recovery of absolute neutrophil count to >/= 500 cells/microL was 11 days (range, 8 to 37 days) for the rituximab group and 10 days (range, 8 to 17 days) for the matched control group (P = .001). However, infections were not significantly increased in patients treated with rituximab. The results of this study suggest that using HD-R and autologous SCT is a feasible and promising treatment for patients with B-cell aggressive NHL.

  13. Cranberry Proanthocyanidins - Protein complexes for macrophage activation.

    Science.gov (United States)

    Carballo, Sergio M; Haas, Linda; Krueger, Christian G; Reed, Jess D

    2017-09-20

    In this work we characterize the interaction of cranberry (Vaccinium macrocarpon) proanthocyanidins (PAC) with bovine serum albumin (BSA) and hen egg-white lysozyme (HEL) and determine the effects of these complexes on macrophage activation and antigen presentation. We isolated PAC from cranberry and complexed the isolated PAC with BSA and HEL. The properties of the PAC-protein complexes were studied by matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS), gel electrophoresis and zeta-potential. The effects of PAC-BSA complexes on macrophage activation were studied in RAW 264.7 macrophage like cells after treatment with lipopolysaccharide (LPS). Fluorescence microscopy was used to study the endocytosis of PAC-BSA complexes. The effects of the PAC complexes on macrophage antigen presentation were studied in an in vitro model of HEL antigen presentation by mouse peritoneal mononuclear cells to a T-cell hybridoma. The mass spectra of the PAC complexes with BSA and HEL differed from the spectra of the proteins alone by the presence of broad shoulders on the singly and doubly charged protein peaks. Complexation with PAC altered the electrophoretic mobility shift assay in native agarose gel and the electrophoretic mobility (ζ-potential) values. These results indicate that the PAC-protein complexes are stable and alter the protein structure without precipitating the protein. Fluorescence microscopy showed that the RAW 264.7 macrophages endocytosed BSA and PAC-BSA complexes in discrete vesicles that surrounded the nucleus. Macrophages treated with increasing amounts of PAC-BSA complexes had significantly reduced COX-2 and iNOS expression in response to treatment with lipopolysaccharide (LPS) in comparison to the controls. The PAC-HEL complexes modulated antigen uptake, processing and presentation in murine peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL

  14. Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

    Science.gov (United States)

    Chistiakov, Dimitry A.; Nikiforov, Nikita G.

    2016-01-01

    Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances. PMID:27493969

  15. Targeting macrophage Histone deacetylase 3 stabilizes atherosclerotic lesions

    NARCIS (Netherlands)

    Hoeksema, Marten A.; Gijbels, Marion J. J.; van den Bossche, Jan; van der Velden, Saskia; Sijm, Ayestha; Neele, Annette E.; Seijkens, Tom; Stöger, J. Lauran; Meiler, Svenja; Boshuizen, Marieke C. S.; Dallinga-Thie, Geesje M.; Levels, Johannes H. M.; Boon, Louis; Mullican, Shannon E.; Spann, Nathanael J.; Cleutjens, Jack P.; Glass, Chris K.; Lazar, Mitchell A.; de Vries, Carlie J. M.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Lutgens, Esther; de Winther, Menno P. J.

    2014-01-01

    Macrophages are key immune cells found in atherosclerotic plaques and critically shape atherosclerotic disease development. Targeting the functional repertoire of macrophages may hold novel approaches for future atherosclerosis management. Here, we describe a previously unrecognized role of the

  16. Macrophages and Their Role in Atherosclerosis: Pathophysiology and Transcriptome Analysis

    Directory of Open Access Journals (Sweden)

    Yuri V. Bobryshev

    2016-01-01

    Full Text Available Atherosclerosis can be regarded as a chronic inflammatory state, in which macrophages play different and important roles. Phagocytic proinflammatory cells populate growing atherosclerotic lesions, where they actively participate in cholesterol accumulation. Moreover, macrophages promote formation of complicated and unstable plaques by maintaining proinflammatory microenvironment. At the same time, anti-inflammatory macrophages contribute to tissue repair and remodelling and plaque stabilization. Macrophages therefore represent attractive targets for development of antiatherosclerotic therapy, which can aim to reduce monocyte recruitment to the lesion site, inhibit proinflammatory macrophages, or stimulate anti-inflammatory responses and cholesterol efflux. More studies are needed, however, to create a comprehensive classification of different macrophage phenotypes and to define their roles in the pathogenesis of atherosclerosis. In this review, we provide an overview of the current knowledge on macrophage diversity, activation, and plasticity in atherosclerosis and describe macrophage-based cellular tests for evaluation of potential antiatherosclerotic substances.

  17. Distribution of macrophage polarization markers in human atherosclerosis

    NARCIS (Netherlands)

    Stöger, J. Lauran; Gijbels, Marion J. J.; van der Velden, Saskia; Manca, Marco; van der Loos, Chris M.; Biessen, Erik A. L.; Daemen, Mat J. A. P.; Lutgens, Esther; de Winther, Menno P. J.

    2012-01-01

    Objective: Macrophages are decisive in the chronic inflammatory processes that drive atherogenesis. The purpose of this study was to explore the presence and spatial distribution of polarized macrophage populations in human atherosclerosis. Methods & results: We used transcriptomics and

  18. Particulate Systems for Targeting of Macrophages: Basic and Therapeutic Concepts

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moien; Parhamifar, Ladan; Ahmadvand, Davoud

    2012-01-01

    Particulate systems in the form of liposomes, polymeric micelles, polymeric nano- and microparticles, and many others offer a rational approach for selective delivery of therapeutic agents to the macrophage from different physiological portals of entry. Particulate targeting of macrophages and in...... at a particular subset of macrophages. Advances in basic and therapeutic concepts of particulate targeting of macrophages and related nanotechnology approaches for immune cell modifications are discussed.Copyright © 2012 S. Karger AG, Basel...

  19. Macrophage phenotype modulation by CXCL4 in vascular disease

    Directory of Open Access Journals (Sweden)

    Christian Albert Gleissner

    2012-01-01

    Full Text Available During atherogenesis, blood monocytes transmigrate into the subendothelial space and differentiate towards macrophages and foam cells. The major driver of this differentiation process is macrophage colony-stimulation factor (M-CSF. M-CSF-induced macrophages are important promoters of atherogenesis as demonstrated in M-CSF and M-CSF receptor knock out mice. However, M-CSF is not the only relevant promoter of macrophage differentiation. The platelet chemokine CXCL4 prevents monocyte apoptosis and promotes macrophage differentiation in vitro. It is secreted from activated platelets and has effects on various cell types relevant in atherogenesis. Knocking out the Pf4 gene coding for CXCL4 in Apoe-/- mice leads to reduced atherogenesis. Thus, it seems likely that CXC4-induced macrophages may have specific pro-atherogenic capacities. We have studied CXC4-induced differentiation of human macrophages using gene chips, systems biology and functional in vitro and ex vivo experiments. Our data indicate that CXCL4-induced macrophages are distinct from both their M-CSF-induced counterparts and other known macrophage polarizations like M1 macrophages (induced by LPS and interferon-gamma or M2 macrophages (induced by interleukin-4. CXCL4-induced macrophages have distinct phenotypic and functional characteristics, e.g. the complete loss of the hemoglobin-haptoglobin (Hb-Hp scavenger receptor CD163 which is necessary for effective hemoglobin clearance after plaque hemorrhage. Lack of CD163 is accompanied by the inability to upregulate the atheroprotective enzyme heme oxygenase-1 in response to Hb-Hp complexes.This review covers the current knowledge about CXCL4-induced macrophages, which based on their unique properties we have suggested to call these macrophages M4. CXCL4 may represent an important driver of macrophage heterogeneity within atherosclerotic lesions. Further dissecting its effects on macrophage differentiation may help to identify novel

  20. Autologous blood stem-cell transplantation in patients with advanced Hodgkin's disease and prior radiation to the pelvic site

    International Nuclear Information System (INIS)

    Koerbling, M.H.; Holle, R.; Haas, R.; Knauf, W.; Doerken, B.H.; Ho, A.D.; Kuse, R.; Pralle, H.; Fliedner, T.M.; Hunstein, W.

    1990-01-01

    Patients with relapsed Hodgkin's disease who respond to salvage therapy are successfully treated with cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) followed by autologus bone marrow transplantation (ABMT). Because of heavy pretreatment including radiation to the pelvic site, marrow harvest was not feasible in those patients. We therefore used blood-derived hemopoietic precursor cells as an alternative stem-cell source to rescue them after superdose chemotherapy. Hemopoietic precursor cells were mobilized into the peripheral blood either by chemotherapeutic induction of transient myelosuppression followed by an overshooting of blood stem-cell concentration, or by continuous intravenous (IV) granulocyte-macrophage colony-stimulating factor (GM-CSF) administration. The median time to reach 1,000 WBC per microliter, 500 polymorphonuclear cells (PMN) per microliter, or 20,000 platelets per microliter was 10, 20.5, and 38 days, respectively, for 50% of all patients. The platelet counts of two patients never dropped below 20,000/microL following autologous blood stem-cell transplantation (ABSCT), whereas two other patients had to be supported with platelets for 75 and 86 days posttransplant until a stable peripheral platelet count of 20,000/microL was attained. Among the 11 assessable patients, seven are in unmaintained complete remission (CR) at a median follow-up of 318 days. This is a first report on a series of ABSCTs in patients with advanced Hodgkin's disease proving that, despite prior damage to the marrow site, the circulating stem-cell pool is still a sufficient source of hemopoietic precursor cells for stem-cell rescue

  1. DMPD: Mechanisms for the anti-inflammatory effects of adiponectin in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18336664 Mechanisms for the anti-inflammatory effects of adiponectin in macrophages...(.html) (.csml) Show Mechanisms for the anti-inflammatory effects of adiponectin in macrophages. PubmedID 18336664 Title Mechanism

  2. Wip1-dependent modulation of macrophage migration and phagocytosis

    DEFF Research Database (Denmark)

    Tang, Yiting; Pan, Bing; Zhou, Xin

    2017-01-01

    macrophage migration and phagocytosis associated with atherosclerotic plaque formation. Wip1 deficiency increases migratory and phagocytic activities of the macrophage under stress conditions. Enhanced migration of Wip1-/- macrophages is mediated by Rac1-GTPase and PI3K/AKT signalling pathways. Elevated...

  3. Bone marrow macrophages support prostate cancer growth in bone.

    Science.gov (United States)

    Soki, Fabiana N; Cho, Sun Wook; Kim, Yeo Won; Jones, Jacqueline D; Park, Serk In; Koh, Amy J; Entezami, Payam; Daignault-Newton, Stephanie; Pienta, Kenneth J; Roca, Hernan; McCauley, Laurie K

    2015-11-03

    Resident macrophages in bone play important roles in bone remodeling, repair, and hematopoietic stem cell maintenance, yet their role in skeletal metastasis remains under investigated. The purpose of this study was to determine the role of macrophages in prostate cancer skeletal metastasis, using two in vivo mouse models of conditional macrophage depletion. RM-1 syngeneic tumor growth was analyzed in an inducible macrophage (CSF-1 receptor positive cells) ablation model (MAFIA mice). There was a significant reduction in tumor growth in the tibiae of macrophage-ablated mice, compared with control non-ablated mice. Similar results were observed when macrophage ablation was performed using liposome-encapsulated clodronate and human PC-3 prostate cancer cells where tumor-bearing long bones had increased numbers of tumor associated-macrophages. Although tumors were consistently smaller in macrophage-depleted mice, paradoxical results of macrophage depletion on bone were observed. Histomorphometric and micro-CT analyses demonstrated that clodronate-treated mice had increased bone volume, while MAFIA mice had reduced bone volume. These results suggest that the effect of macrophage depletion on tumor growth was independent of its effect on bone responses and that macrophages in bone may be more important to tumor growth than the bone itself. In conclusion, resident macrophages play a pivotal role in prostate cancer growth in bone.

  4. Markers of mouse macrophage development detected by monoclonal antibodies

    NARCIS (Netherlands)

    P.J. Leenen (Pieter); M.F.T.R. de Bruijn (Marella F.T.R); J.S. Voerman (Jane); P.A. Campbell (Priscilla); W. van Ewijk (Willem)

    1994-01-01

    textabstractIn this review, we present and discuss a selected panel of antibody-defined markers expressed during different stages of mouse macrophage development. We distinguish four categories of markers, which are characteristic of: (1) macrophage precursors and immature macrophages (ER-MP12,

  5. Drug Trafficking into Macrophages via the Endocytotic Receptor CD163

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Moestrup, Søren Kragh

    2015-01-01

    In inflammatory diseases, macrophages are a main producer of a range of cytokines regulating the inflammatory state. This also includes inflammation induced by tumor growth, which recruits so-called tumor-associated macrophages supporting tumor growth. Macrophages are therefore relevant targets f...

  6. The changes in hair growth pattern after autologous hair transplantation.

    Science.gov (United States)

    Lee, S H; Kim, D W; Jun, J B; Lee, S J; Kim, J C; Kim, N H

    1999-08-01

    Recently donor dominance has been emphasized in autologous hair transplantation while the influence of the recipient site has been considered negligible. In fact, there have been few studies that show this. This study was performed to examine the influence of the recipient site on transplanted hairs. A clinical study of 19 leprosy patients was performed. These patients had received single hair transplantation due to madarosis and were admitted to The Leprosy Mission, Jesus Hospital, Taegu, Korea, or had visited its outpatient clinic. In this study, the rate of growth, thickness of shaft, and graying rate between the transplanted eyebrow hair in the recipient site and scalp hair near the donor site were compared to observe the changes in the growth pattern of the hairs after transplantation. For most of the patients, the growth rate and graying rate of transplanted hairs were lower than those of hairs in the donor site. It seems that the recipient site may have an influence on the transplanted hairs. Further studies are needed, including clinical, histopathologic, and molecular biological methods.

  7. Quality Improvement Methodologies Increase Autologous Blood Product Administration

    Science.gov (United States)

    Hodge, Ashley B.; Preston, Thomas J.; Fitch, Jill A.; Harrison, Sheilah K.; Hersey, Diane K.; Nicol, Kathleen K.; Naguib, Aymen N.; McConnell, Patrick I.; Galantowicz, Mark

    2014-01-01

    Abstract: Whole blood from the heart–lung (bypass) machine may be processed through a cell salvaging device (i.e., cell saver [CS]) and subsequently administered to the patient during cardiac surgery. It was determined at our institution that CS volume was being discarded. A multidisciplinary team consisting of anesthesiologists, perfusionists, intensive care physicians, quality improvement (QI) professionals, and bedside nurses met to determine the challenges surrounding autologous blood delivery in its entirety. A review of cardiac surgery patients’ charts (n = 21) was conducted for analysis of CS waste. After identification of practices that were leading to CS waste, interventions were designed and implemented. Fishbone diagram, key driver diagram, Plan–Do–Study–Act (PDSA) cycles, and data collection forms were used throughout this QI process to track and guide progress regarding CS waste. Of patients under 6 kg (n = 5), 80% had wasted CS blood before interventions, whereas those patients larger than 36 kg (n = 8) had 25% wasted CS before interventions. Seventy-five percent of patients under 6 kg who had wasted CS blood received packed red blood cell transfusions in the cardiothoracic intensive care unit within 24 hours of their operation. After data collection and didactic education sessions (PDSA Cycle I), CS blood volume waste was reduced to 5% in all patients. Identification and analysis of the root cause followed by implementation of education, training, and management of change (PDSA Cycle II) resulted in successful use of 100% of all CS blood volume. PMID:24783313

  8. Micro-Autologous Fat Transplantation for Treating a Gummy Smile.

    Science.gov (United States)

    Huang, Shu-Hung; Huang, Yu-Hao; Lin, Yun-Nan; Lee, Su-Shin; Chou, Chih-Kang; Lin, Tsung-Ying; Takahashi, Hidenobu; Kuo, Yur-Ren; Lai, Chung-Sheng; Lin, Sin-Daw; Lin, Tsai-Ming

    2018-03-16

    A gummy smile is treated using a number of techniques, including botulinum toxin injection and various surgical interventions. Micro-autologous fat transplantation (MAFT) is a potentially advantageous alternative approach that has not been previously evaluated. This study sought to determine the long-term results of MAFT in patients with a gummy smile. Seven patients with gummy smiles were evaluated for MAFT treatment between October 2015 and April 2017. Centrifuged purified fat was micro-transplanted into the nasolabial groove, ergotrid, and upper lip areas using the MAFT-GUN while the patients were under total intravenous anesthesia. The mean age of the 7 patients was 31 years (range, 23-40 years). The mean operating time for MAFT was 52 minutes (range, 40-72 minutes), and the mean volume of fat delivered to the nasolabial groove, ergotrid, and upper lip was 16.1 mL. The mean decreases of gingival display in the right canine incisor, left canine incisor, right canine, and left canine teeth were 4.9, 4.6, 3.8, and 4.4 mm, respectively. The smiles of the 7 patients showed significant improvement at an average follow-up time of 12.9 months. Gummy smile treatment using MAFT is an effective, reliable, and relatively simple method, with high patient satisfaction and minimal risk of complications.

  9. Autologous Platelet-rich Plasma after Third Molar Surgery.

    Science.gov (United States)

    Gandevivala, Adil; Sangle, Amit; Shah, Dinesh; Tejnani, Avneesh; Sayyed, Aatif; Khutwad, Gaurav; Patel, Arpit Arunbhai

    2017-01-01

    The aim of this study is to compare the efficacy of autologous platelet-rich plasma (PRP) in the third molar impactions, with respect to: pain, swelling, healing, and periodontal status distal to the second molar in patients who need surgical removal of bilateral impacted mandibular third molars. Twenty-five patients of both sexes aged between 16 and 60 years who required bilateral surgical removal of their impacted third molars and met the inclusion criteria were included in the study. After surgical extraction of the third molar, primary closure was performed in the control group, whereas PRP was placed in the socket followed by primary closure in the case group. The outcome variables were pain, swelling, wound healing, and periodontal probe depth that were follow-up period of 2 months. Quantitative data are presented as mean. Statistical significance was checked by t -test. There was a difference in the pain (0.071) and facial swelling (0.184), reduction between test and control on day 3, but it was not found to be significant. Periodontal pocket depth (0.001) and wound healing (0.001) less in case group compared with the control group was found to be significant. The use of PRP lessens the severity of immediate postoperative sequelae and decreases preoperative pocket depth.

  10. Tissue engineering bone using autologous progenitor cells in the peritoneum.

    Science.gov (United States)

    Shen, Jinhui; Nair, Ashwin; Saxena, Ramesh; Zhang, Cheng Cheng; Borrelli, Joseph; Tang, Liping

    2014-01-01

    Despite intensive research efforts, there remains a need for novel methods to improve the ossification of scaffolds for bone tissue engineering. Based on a common phenomenon and known pathological conditions of peritoneal membrane ossification following peritoneal dialysis, we have explored the possibility of regenerating ossified tissue in the peritoneum. Interestingly, in addition to inflammatory cells, we discovered a large number of multipotent mesenchymal stem cells (MSCs) in the peritoneal lavage fluid from mice with peritoneal catheter implants. The osteogenic potential of these peritoneal progenitor cells was demonstrated by their ability to easily infiltrate decalcified bone implants, produce osteocalcin and form mineralized bone in 8 weeks. Additionally, when poly(l-lactic acid) scaffolds loaded with bone morphogenetic protein-2 (a known osteogenic differentiation agent) were implanted into the peritoneum, signs of osteogenesis were seen within 8 weeks of implantation. The results of this investigation support the concept that scaffolds containing BMP-2 can stimulate the formation of bone in the peritoneum via directed autologous stem and progenitor cell responses.

  11. Quality improvement methodologies increase autologous blood product administration.

    Science.gov (United States)

    Hodge, Ashley B; Preston, Thomas J; Fitch, Jill A; Harrison, Sheilah K; Hersey, Diane K; Nicol, Kathleen K; Naguib, Aymen N; McConnell, Patrick I; Galantowicz, Mark

    2014-03-01

    Whole blood from the heart-lung (bypass) machine may be processed through a cell salvaging device (i.e., cell saver [CS]) and subsequently administered to the patient during cardiac surgery. It was determined at our institution that CS volume was being discarded. A multidisciplinary team consisting of anesthesiologists, perfusionists, intensive care physicians, quality improvement (QI) professionals, and bedside nurses met to determine the challenges surrounding autologous blood delivery in its entirety. A review of cardiac surgery patients' charts (n = 21) was conducted for analysis of CS waste. After identification of practices that were leading to CS waste, interventions were designed and implemented. Fishbone diagram, key driver diagram, Plan-Do-Study-Act (PDSA) cycles, and data collection forms were used throughout this QI process to track and guide progress regarding CS waste. Of patients under 6 kg (n = 5), 80% had wasted CS blood before interventions, whereas those patients larger than 36 kg (n = 8) had 25% wasted CS before interventions. Seventy-five percent of patients under 6 kg who had wasted CS blood received packed red blood cell transfusions in the cardiothoracic intensive care unit within 24 hours of their operation. After data collection and didactic education sessions (PDSA Cycle I), CS blood volume waste was reduced to 5% in all patients. Identification and analysis of the root cause followed by implementation of education, training, and management of change (PDSA Cycle II) resulted in successful use of 100% of all CS blood volume.

  12. Rapid cell separation with minimal manipulation for autologous cell therapies

    Science.gov (United States)

    Smith, Alban J.; O'Rorke, Richard D.; Kale, Akshay; Rimsa, Roberts; Tomlinson, Matthew J.; Kirkham, Jennifer; Davies, A. Giles; Wälti, Christoph; Wood, Christopher D.

    2017-02-01

    The ability to isolate specific, viable cell populations from mixed ensembles with minimal manipulation and within intra-operative time would provide significant advantages for autologous, cell-based therapies in regenerative medicine. Current cell-enrichment technologies are either slow, lack specificity and/or require labelling. Thus a rapid, label-free separation technology that does not affect cell functionality, viability or phenotype is highly desirable. Here, we demonstrate separation of viable from non-viable human stromal cells using remote dielectrophoresis, in which an electric field is coupled into a microfluidic channel using shear-horizontal surface acoustic waves, producing an array of virtual electrodes within the channel. This allows high-throughput dielectrophoretic cell separation in high conductivity, physiological-like fluids, overcoming the limitations of conventional dielectrophoresis. We demonstrate viable/non-viable separation efficacy of >98% in pre-purified mesenchymal stromal cells, extracted from human dental pulp, with no adverse effects on cell viability, or on their subsequent osteogenic capabilities.

  13. Autologous miniature punch skin grafting in stable vitiligo

    Directory of Open Access Journals (Sweden)

    Savant S

    1992-01-01

    Full Text Available Autologous split thickness miniature punch skin grafting is one of the surgical modes of treatment of stable vitiligo. Out of 87 different sites, of stable vitiligo, occurring in 62 cases, (32 focal, 22 segmental and 8 generalised 75 sites showed total repigmentation with excellent cosmetic colour match. Out of the 62 cases, 46 cases who were treated postsurgically with PUVA therapy repigmented within 2 ½ to 3 months, 10 cases, who received no treatment postsurgically repigmented by 3 ½ to 6 months. In addition 6 cases in whom no treatment was given postsurgically had to be given PUVA therapy 3 months after surgery as there was poor repigmentation. The complications seen were graft rejection due to improper immobilization in 6 cases, graft rejection due to secondary infection in 1, contact allergic dermatitis to framycetin in 3, and reactivation of vitiligo in 2. Side effects seen were cobblestoning in 32, sinking pits in 12, variegated appearance in 4, and superficial scarring at donor site in all 62 cases.

  14. Sublabial Autologous Ear Cartilage Grafting for Increasing the Nasolabial Angle

    Directory of Open Access Journals (Sweden)

    Rajko Toncic

    2016-01-01

    Full Text Available BackgroundThe loss of nasal tip support is caused by many factors and eventually results in the collapse and eventual dropping of the nasal tip. This reduces the nasolabial (NL angle and negatively affects respiratory functions and one's appearance.MethodsThe aim of this retrospective study, which was conducted on 52 patients, was to present and popularize a simple and effective method for the reconstruction of a weakened columella by inserting an autologous ear cartilage graft using a sublabial approach.ResultsOf all the patients, three patients experienced transplant rejection. The period of follow-up observation was one to five years (mean, 27 months. The results were objectively evaluated by measuring the NL angle in standardized photos before and after the procedure at different time intervals over the follow-up period. We observed a significant increase of the NL angle (mean, 20°, and found these results to be durable over the long term. Of the 52 patients included in this study observed patients, three were dissatisfied (due to immediate infection and shifting of the strut, 28 were satisfied, and 21 were very satisfied.ConclusionsThe surgical method described here is simple and can be learned quickly. It has very good results with few complications, and is our method of choice for complex and serious cases seen in everyday rhinosurgical practice.

  15. Sleep disruption among cancer patients following autologous hematopoietic cell transplantation.

    Science.gov (United States)

    Nelson, Ashley M; Jim, Heather S L; Small, Brent J; Nishihori, Taiga; Gonzalez, Brian D; Cessna, Julie M; Hyland, Kelly A; Rumble, Meredith E; Jacobsen, Paul B

    2018-03-01

    Despite a high prevalence of sleep disruption among hematopoietic cell transplant (HCT) recipients, relatively little research has investigated its relationships with modifiable cognitive or behavioral factors or used actigraphy to characterize sleep disruption in this population. Autologous HCT recipients who were 6-18 months post transplant completed self-report measures of cancer-related distress, fear of cancer recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors upon enrollment. Patients then wore an actigraph for 7 days and completed a self-report measure of sleep disruption on day 7 of the study. Among the 84 participants (age M = 60, 45% female), 41% reported clinically relevant sleep disruption. Examination of actigraph data confirmed that, on average, sleep was disrupted (wake after sleep onset M = 66 min) and sleep efficiency was less than recommended (sleep efficiency M = 78%). Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and inhibitory sleep behaviors were related to self-reported sleep disruption (p valuesdisruption after transplant. Cancer-related distress, fear of recurrence, dysfunctional sleep cognitions, and maladaptive sleep behaviors are related to self-reported sleep disruption and should be considered targets for cognitive behavioral intervention in this population.

  16. Complement activated granulocytes can cause autologous tissue destruction in man

    Directory of Open Access Journals (Sweden)

    E. Löhde

    1992-01-01

    Full Text Available Activation of polymorphonuclear granulocytes (PMNs by C5a is thought to be important in the pathogenesis of multiple organ failure during sepsis and after trauma. In our experiment exposure of human PMNs to autologous zymosan activated plasma (ZAP leads to a rapid increase in chemiluminescence. Heating the ZAP at 56°C for 30 min did not alter the changes, while untreated plasma induced only baseline activity. The respiratory burst could be completely abolished by decomplementation and preincubation with rabbit antihuman C5a antibodies. Observation of human omentum using electron microscopy showed intravascular aggregation of PMNs, with capillary thrombosis and diapedesis of the cells through endothelial junctions 90 s after exposure to ZAP. PMNs caused disruption of connections between the mesothelial cells. After 4 min the mesothelium was completely destroyed, and connective tissue and fat cells exposed. Native plasma and minimum essential medium did not induce any morphological changes. These data support the concept that C5a activated PMNs can cause endothelial and mesothelial damage in man. Even though a causal relationship between anaphylatoxins and organ failure cannot be proved by these experiments C5a seems to be an important mediator in the pathogenesis of changes induced by severe sepsis and trauma in man.

  17. Electrospun poly(hydroxybutyrate) scaffolds promote engraftment of human skin equivalents via macrophage M2 polarization and angiogenesis.

    Science.gov (United States)

    Castellano, Delia; Sanchis, Ana; Blanes, María; Pérez Del Caz, Mª Dolores; Ruiz-Saurí, Amparo; Piquer-Gil, Marina; Pelacho, Beatriz; Marco, Bruno; Garcia, Nahuel; Ontoria-Oviedo, Imelda; Cambra, Vicente; Prosper, Felipe; Sepúlveda, Pilar

    2018-02-01

    Human dermo-epidermal skin equivalents (DE) comprising in vitro expanded autologous keratinocytes and fibroblasts are a good option for massive burn treatment. However, the lengthy expansion time required to obtain sufficient surface to cover an extensive burn together with the challenging surgical procedure limits their clinical use. The integration of DE and biodegradable scaffolds has been proposed in an effort to enhance their mechanical properties. Here, it is shown that poly(hydroxybutyrate) electrospun scaffolds (PHB) present good biocompatibility both in vitro and in vivo and are superior to poly-ε-caprolactone electrospun scaffolds as a substrate for skin reconstruction. Implantation of PHB scaffolds in healthy rats polarized macrophages to an M2-type that promoted constructive in vivo remodelling. Moreover, implantation of DE-PHB composites in a NOD/SCID mouse xenograft model resulted in engraftment accompanied by an increase in angiogenesis that favoured the survival of the human graft. Thus, PHB scaffolds are an attractive substrate for further exploration in skin reconstruction procedures, probably due in part to their greater angiogenic and M2 macrophage polarization properties. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Proprotein convertase 1/3 inhibited macrophages: A novel therapeutic based on drone macrophages

    Directory of Open Access Journals (Sweden)

    Marie Duhamel

    2016-06-01

    Full Text Available We demonstrated here thanks to proteomic, that proprotein convertase 1/3 knockdown macrophages present all the characteristic of activated pro-inflammatory macrophages. TLR4 and TLR9 signaling pathways can be enhanced leading to the secretion of pro-inflammatory factors and antitumor factors. We can control their activation by controlling one enzyme, PC1/3. In a tumor context, PC1/3 inhibition in macrophages may reactivate them and lead to a cytokine storm after stimulation “at distance” with a TLR ligand. Therefore, we name these proprotein convertase inhibited macrophages the “drone macrophages”. They constitute an innovative cell therapy to treat efficiently tumors.

  19. Long-term use and follow-up of autologous and homologous cartilage graft in rhinoplasty

    Directory of Open Access Journals (Sweden)

    Ghasemali Khorasani

    2016-05-01

    Full Text Available Background: Cartilage grafting is used in rhinoplasty and reconstructive surgeries. Autologous rib and nasal septum cartilage (auto graft is the preferred source of graft material in rhinoplasty, however, homologous cartilage (allograft has been extensively used to correct the nasal framework in nasal deformities. Autologous cartilage graft usage is restricted with complication of operation and limiting availability of tissue for extensive deformities. Alternatively, preserved costal cartilage allograft represents a readily available and easily contoured material. The current study was a formal systematic review of complications associated with autologous versus homologous cartilage grafting in rhinoplasty patients. Methods: In this cohort retrospective study, a total of 124 patients undergone primary or revision rhinoplasty using homologous or autologus grafts with postoperative follow-up ranging from 6 to 60 months were studied. The types of grafts and complications related to the grafts were evaluated. This included evaluation for warping, infection, resorption, mobility and fracture. Results: The total complications related to the cartilage grafts were 7 cases, which included 1 warped in auto graft group, three cases of graft displacement (two in allograft group and one in auto graft group and three fractures in allograft group. No infection and resorption was recorded. Complication rate (confidence interval 0.95 in autologous and homologous group were 1.25(0.4-3.88 and 2.08(0.78-5.55 in 1000 months follow up. There was no statistically significant difference between autologous and homologous group complications. Onset of complication in autologous and homologous group were 51.23(49.27-53.19 and 58.7(54.51-62.91 month respectively (P=0.81. Conclusion: The allograft cartilage has the advantage of avoiding donor-site scar. Moreover, it provides the same benefits as autologous costal cartilage with comparable complication rate. Therefore, it

  20. Macrophage Migration Inhibitory Factor in Protozoan Infections

    Directory of Open Access Journals (Sweden)

    Marcelo T. Bozza

    2012-01-01

    Full Text Available Macrophage migration inhibitory factor (MIF is a cytokine that plays a central role in immune and inflammatory responses. In the present paper, we discussed the participation of MIF in the immune response to protozoan parasite infections. As a general trend, MIF participates in the control of parasite burden at the expense of promoting tissue damage due to increased inflammation.

  1. Possible macrophage activation syndrome following initiation of ...

    African Journals Online (AJOL)

    Macrophage activation syndrome (MAS) has been rarely reported in the course of adult-onset Still's disease (AOSD) and in the majority of cases, it was triggered by an infection. Here, we report, to our knowledge, the first case of MAS occurring after adalimumab treatment initiation and not triggered by an infection.

  2. Metabolic-epigenetic crosstalk in macrophage activation

    NARCIS (Netherlands)

    Baardman, Jeroen; Licht, Iris; de Winther, Menno P. J.; van den Bossche, Jan

    2015-01-01

    Epigenetic enzymes are emerging as crucial controllers of macrophages, innate immune cells that determine the outcome of many inflammatory diseases. Recent studies demonstrate that the activity of particular chromatin-modifying enzymes is regulated by the availability of specific metabolites like

  3. Atherosclerosis & inflammation: Macrophage heterogeneity in focus

    NARCIS (Netherlands)

    Stöger, J.L.

    2014-01-01

    Macrophages characteristically feature a considerable degree of heterogeneity and plasticity to accommodate for the enormous variety in stimuli and challenges that their microenvironment presents them with. By virtue of their activation status, these cells can be classified into one of several

  4. Degradation of parathyroid hormone in macrophage endosomes

    International Nuclear Information System (INIS)

    Diment, S.; Martin, K.J.; Stahl, P.D.

    1986-01-01

    Parathyroid hormone (PTH) is secreted as an 84 amino acid protein that is rapidly cleaved between amino acids 34 and 35 by Kupffer cells in liver. The resulting amino terminal peptide (1-34) is active at PTH target organs (kidney and bone). Cathepsin D can process PTH to 1-34 in vitro, and a cathepsin D-like protease, which may rapidly process proteins, is present in endosomes of alveolar macrophages. The authors set out to determine whether PTH is degraded to 1-34 in endosomes, and to elucidate the mechanism of hormone processing in vivo. Intracellular transport of 125 I-PTH was assessed by binding to alveolar macrophages at 4 0 C, followed by internalization at 37 0 C. Distribution of PTH among plasma membranes, endosomes and lysosomes was determined by subcellular fractionation. Degradation of the ligand to TCA-soluble fragments in each compartment was assayed at neutral and acid pH. 1-34 in supernatants was separated from undergraded PTH by gel filtration and detected by bioassay on kidney membranes. The authors data suggest that: 1) macrophages rapidly degrade PTH to TCA-soluble fragments. 2) macrophages do not secrete proteases that degrade extracellular PTH. 3) PTH is internalized into endocytic vesicles after 5 mins, but not delivered to lysosomes within 30 mins. 4) A bioactive peptide is released into the extracellular medium after 20 mins. 5) PTH is degraded in endosomes at acid pH by a pepstatin-sensitive protease

  5. The macrophage scavenger receptor CD163

    NARCIS (Netherlands)

    Fabriek, Babs O.; Dijkstra, Christine D.; van den Berg, Timo K.

    2005-01-01

    Mature tissue macrophages form a first line of defense to recognize and eliminate potential pathogens; these specialized cells are capable of phagocytosis, degradation of self and foreign materials, establishment of cell-cell interactions, and the production of inflammatory mediators. Mature tissue

  6. Macrophage serum markers in pneumococcal bacteremia

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Moestrup, Søren K; Weis, Nina

    2006-01-01

    OBJECTIVE: Soluble CD163 (sCD163) is a new macrophage-specific serum marker. This study investigated sCD163 and other markers of macrophage activation (neopterin, ferritin, transcobalamin, and soluble urokinase plasminogen activator receptor [suPAR]) as prognostic factors in patients...... analyses at the time of first positive blood culture. MEASUREMENTS AND MAIN RESULTS: sCD163 was highly correlated with other macrophage markers and was significantly elevated (median [25-75 percentiles], 4.6 mg/L [2.8-8.9]) compared with healthy controls (2.7 mg/L [2.1-3.3], p ..., all macrophage markers were increased in patients who died from their infection compared with survivors, whereas no change was observed in any of the markers in the very old age. At cutoff levels of 9.5 mg/L (sCD163) and 1650 nmol/L (C-reactive protein), the relative risk for fatal outcome in patients...

  7. Soluble macrophage-derived CD163

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Nielsen, Marianne Jensby; Maniecki, Maciej Bogdan

    2010-01-01

    BACKGROUND: The soluble form of the haptoglobin-hemoglobin (Hp-Hb) scavenger receptor (sCD163) is a specific plasma/serum marker for macrophage activity. Here, we have characterized molecular forms in serum and investigated a role of sCD163 as a binder of Hp-Hb complexes. METHODS: The sCD163...

  8. Mouse adenovirus type 1 infection of macrophages

    NARCIS (Netherlands)

    Ashley, S.L.; Welton, A.R.; Harwood, K.M.; Rooijen, van N.; Spindler, K.R.

    2009-01-01

    Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus.

  9. Ameobal pathogen mimivirus infects macrophages through phagocytosis.

    Directory of Open Access Journals (Sweden)

    Eric Ghigo

    2008-06-01

    Full Text Available Mimivirus, or Acanthamoeba polyphaga mimivirus (APMV, a giant double-stranded DNA virus that grows in amoeba, was identified for the first time in 2003. Entry by phagocytosis within amoeba has been suggested but not demonstrated. We demonstrate here that APMV was internalized by macrophages but not by non-phagocytic cells, leading to productive APMV replication. Clathrin- and caveolin-mediated endocytosis pathways, as well as degradative endosome-mediated endocytosis, were not used by APMV to invade macrophages. Ultrastructural analysis showed that protrusions were formed around the entering virus, suggesting that macropinocytosis or phagocytosis was involved in APMV entry. Reorganization of the actin cytoskeleton and activation of phosphatidylinositol 3-kinases were required for APMV entry. Blocking macropinocytosis and the lack of APMV colocalization with rabankyrin-5 showed that macropinocytosis was not involved in viral entry. Overexpression of a dominant-negative form of dynamin-II, a regulator of phagocytosis, inhibited APMV entry. Altogether, our data demonstrated that APMV enters macrophages through phagocytosis, a new pathway for virus entry in cells. This reinforces the paradigm that intra-amoebal pathogens have the potential to infect macrophages.

  10. Alternatively Activated (M2 Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

    Directory of Open Access Journals (Sweden)

    Stefano Soldano

    Full Text Available Alternatively activated (M2 macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163 and mannose receptor-1 (CD206, and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1 and metalloproteinase (MMP-9. Endothelin-1 (ET-1 is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB. The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells.Cultured human monocytes (THP-1 cell line were activated into macrophages (M0 macrophages with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls or treated with either ET-1 (100nM or interleukin-4 (IL-4, 10ng/mL, M2 inducer for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR. Gene expression of interleukin(IL-10 and macrophage derived chemokine (CCL-22 was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography.ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

  11. Tumour macrophages as potential targets of bisphosphonates

    Science.gov (United States)

    2011-01-01

    Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use. Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to

  12. Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control

    NARCIS (Netherlands)

    Fink, K.; Ng, C.; Nkenfou, C.; Vasudevan, S.G.; Rooijen, van N.; Schul, W.

    2009-01-01

    Monocytes and macrophages are target cells for dengue infection. Besides their potential role for virus replication, activated monocytes/macrophages produce cytokines that may be critical for dengue pathology. To study the in vivo role of monocytes and macrophages for virus replication, we depleted

  13. DMPD: Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signalingpathways. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12960231 Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited sign...82. Epub 2003 Jul 22. (.png) (.svg) (.html) (.csml) Show Macrophage activation through CCR5- and CXCR4-media...ted gp120-elicited signalingpathways. PubmedID 12960231 Title Macrophage activation through CCR

  14. DMPD: Molecular mechanisms of macrophage activation and deactivation bylipopolysaccharide: roles of the receptor complex. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 14609719 Molecular mechanisms of macrophage activation and deactivation bylipopolys...acol Ther. 2003 Nov;100(2):171-94. (.png) (.svg) (.html) (.csml) Show Molecular mechanisms of macrophage act...ivation and deactivation bylipopolysaccharide: roles of the receptor complex. PubmedID 14609719 Title Mole...cular mechanisms of macrophage activation and deactivation bylipopolysaccharide: ro

  15. DMPD: Genetic regulation of macrophage priming/activation: the Lsh gene story. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 1757110 Genetic regulation of macrophage priming/activation: the Lsh gene story. Bl... (.svg) (.html) (.csml) Show Genetic regulation of macrophage priming/activation: the Lsh gene story. Pubmed...ID 1757110 Title Genetic regulation of macrophage priming/activation: the Lsh gen

  16. DMPD: Pathogen-induced apoptosis of macrophages: a common end for different pathogenicstrategies. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 11207583 Pathogen-induced apoptosis of macrophages: a common end for different path...ml) Show Pathogen-induced apoptosis of macrophages: a common end for different pathogenicstrategies. PubmedI...D 11207583 Title Pathogen-induced apoptosis of macrophages: a common end for diff

  17. Yersinia pestis and host macrophages: immunodeficiency of mouse macrophages induced by YscW.

    Science.gov (United States)

    Bi, Yujing; Du, Zongmin; Han, Yanping; Guo, Zhaobiao; Tan, Yafang; Zhu, Ziwen; Yang, Ruifu

    2009-09-01

    The virulence of the pathogenic Yersinia species depends on a plasmid-encoded type III secretion system (T3SS) that transfers six Yersinia outer protein (Yop) effector proteins into the cytoplasm of eukaryotic cells, leading to disruption of host defence mechanisms. It is shown in this study that Yersinia pestis YscW, a protein of the T3SS injectisome, contributes to the induction of a deficiency in phagocytosis in host macrophages and a reduction in their antigen-presenting capacity. A Y. pestis strain lacking yscW had no effect on uptake by host macrophages. In mice infected with wild-type Y. pestis, the yscW mutant or a complement strain, immunodeficiency was observed in host macrophages compared with those from uninfected mice. However, the phagocytosis and antigen presenting capacities of macrophages infected by yscW mutant strain both in vivo and in vitro were significantly higher than those by wild type strain. Consistent with this finding, when YscW was expressed in the RAW264.7 macrophage cell line, phagocytosis and antigen-presenting capacities were significantly lower than those of the control groups. These results indicate that Y. pestis YscW may directly induce immunodeficiency in murine macrophages by crippling their phagocytosis and antigen-presenting capacities. These data provide evidences to Y. pestis pathogenesis that some proteins in T3SS injectisome, such as YscW protein, might play independent roles in disrupting host defense apart from their known functions.

  18. Effects of nanoparticles on murine macrophages

    Science.gov (United States)

    Chevallet, M.; Aude-Garcia, C.; Lelong, C.; Candéias, S.; Luche, S.; Collin-Faure, V.; Triboulet, S.; Diallo, D.; Diemer, H.; van Dorsselaer, A.; Rabilloud, T.

    2011-07-01

    Metallic nanoparticles are more and more widely used in an increasing number of applications. Consequently, they are more and more present in the environment, and the risk that they may represent for human health must be evaluated. This requires to increase our knowledge of the cellular responses to nanoparticles. In this context, macrophages appear as an attractive system. They play a major role in eliminating foreign matter, e.g. pathogens or infectious agents, by phagocytosis and inflammatory responses, and are thus highly likely to react to nanoparticles. We have decided to study their responses to nanoparticles by a combination of classical and wide-scope approaches such as proteomics. The long term goal of this study is the better understanding of the responses of macrophages to nanoparticles, and thus to help to assess their possible impact on human health. We chose as a model system bone marrow-derived macrophages and studied the effect of commonly used nanoparticles such as TiO2 and Cu. Classical responses of macrophage were characterized and proteomic approaches based on 2D gels of whole cell extracts were used. Preliminary proteomic data resulting from whole cell extracts showed different effects for TiO2-NPs and Cu-NPs. Modifications of the expression of several proteins involved in different pathways such as, for example, signal transduction, endosome-lysosome pathway, Krebs cycle, oxidative stress response have been underscored. These first results validate our proteomics approach and open a new wide field of investigation for NPs impact on macrophages.

  19. Inhibition of HIV-1 replication in macrophages by red blood cell-mediated delivery of a heterodinucleotide of azidothymidine and 9-(R)-2-(phosphono methoxypropyl)adenine.

    Science.gov (United States)

    Franchetti, P; Rossi, L; Cappellacci, L; Pasqualini, M; Grifantini, M; Balestra, E; Forbici, F; Perno, C F; Serafini, S; Magnani, M

    2001-05-01

    Monocyte-derived macrophages (M/M) are considered important in vivo reservoirs for different kinds of viruses, including HIV. Hence, therapeutic strategies are urgently needed to protect these cells from virus infection or to control viral replication. In this paper, we report the synthesis, target delivery and in vitro efficacy of a new heterodinucleotide (AZTpPMPA), able to inhibit HIV-1 production in human macrophages. AZTpPMPA consists of two established anti-HIV drugs [zidovudine (AZT) and tenofovir (PMPA)] chemically coupled together by a phosphate bridge. This drug is not able to prevent p24 production when administered for 18 h to M/M experimentally infected with HIV-1 Bal (inhibition 27%), but can almost completely suppress virus production when given encapsulated into autologous erythrocytes (inhibition of p24 production 97%). AZTpPMPA is slowly converted to PMPA, AZT monophosphate and AZT (36 h half-life at 37 degrees C) by cell-resident enzymes. Thus AZTpPMPA should be considered a new prodrug of AZT and PMPA that is able to provide stechiometric amounts of both nucleoside analogues to macrophage cells and to overcome the low phosphorylating activity of M/M for AZT and the modest permeability of PMPA.

  20. Sports Activity After Reconstruction of Osteochondral Lesions of the Talus With Autologous Spongiosa Grafts and Autologous Matrix-Induced Chondrogenesis.

    Science.gov (United States)

    Wiewiorski, Martin; Werner, Lorenzo; Paul, Jochen; Anderson, Andrew E; Barg, Alexej; Valderrabano, Victor

    2016-10-01

    For the treatment of osteochondral lesions of the talus (OCLTs), autologous matrix-induced chondrogenesis (AMIC) is a safe 1-step procedure with good clinical and radiological results. However, data regarding postoperative sports activity after AMIC are limited. To identify significant factors influencing the rate of postoperative sports and recreational activities. Case series; Level of evidence, 4. The sports and recreational activities of 60 patients (mean age, 34.9 ± 11.5 years) undergoing the AMIC procedure were retrospectively analyzed at a mean of 46.9 ± 17.8 months (range, 24.5-87.0 months) postoperatively. The visual analog scale (VAS) for pain score, Tegner activity scale score, activity rating scale (ARS) score, and satisfaction with surgery outcomes were assessed. Corrective calcaneal osteotomy was performed in 38 of 60 (63.3%) patients. Ligament repair was performed in 41 of 60 (68.3%) patients. The mean VAS score improved significantly from 6.9 ± 1.6 points (range, 5-10 points) preoperatively to 2.3 ± 1.9 points (range, 0-6 points) at latest follow-up (P sports activity before the onset of symptoms became significantly lower at the time of surgery (from 95.0% to 53.3%; P sports frequency and the duration of sports activity was found postoperatively. Patients undergoing AMIC repair of an OCLT participate at a similar low postoperative sports and recreational activity level compared with the preoperative level. © 2016 The Author(s).

  1. Anticryptococcal activity of amphotericin B-stimulated macrophages.

    Science.gov (United States)

    Aslanzadeh, J; Mormol, J S; Little, J R

    1991-01-01

    Amphotericin B (AmB) and its methyl ester derivative (AME) are immunoadjuvants with macrophage stimulating properties. Cultures containing AmB and murine peritoneal macrophages showed synergistic anticryptococcal activity. The antifungal activity was associated with AmB-stimulated macrophages and with their culture supernatants. Photoinactivation of the residual AmB in the macrophage culture supernatant did not result in the loss of antifungal activity. AmB-stimulated macrophage culture supernatants inhibited the growth of C. neoformans in a dose responsive manner and the activity was destroyed by incubation at 100 degrees C but not at 60 degrees C.

  2. Preeclampsia in autologous and oocyte donation pregnancy: is there a different pathophysiology?

    Science.gov (United States)

    Lashley, Lisa E E L O; Buurma, Aletta; Swings, Godelieve M J S; Eikmans, Michael; Anholts, Jacqueline D H; Bakker, Jaap A; Claas, Frans H J

    2015-06-01

    Oocyte donation (OD) is a specific method of artificial reproductive technology that is accompanied by a higher risk of preeclampsia during pregnancy. The pathophysiological mechanism underlying preeclampsia in OD pregnancies is thought to differ from preeclampsia in autologous pregnancies. As preeclampsia in autologous pregnancies is suggested to be associated with complement activation, we studied C4d deposition, circulating complement components and placental complement regulatory proteins in preeclamptic OD pregnancies. Women with uncomplicated and preeclamptic pregnancies after OD or spontaneous conception were selected. We stained the placentas for C4d, marker for complement activation, measured complement factors C1q, C3 and C4 in maternal sera and quantified the placental mRNA expression of complement regulatory proteins CD46, CD55 and CD59. A significantly (p preeclampsia compared with uncomplicated pregnancies, both OD and autologous. The level of complement factors in serum did not differ between the groups. Children born in the autologous preeclampsia group were significantly lower in birth weight (p preeclampsia pregnancies, there is excessive activation of complement in preeclamptic OD pregnancies. However, in contrast to autologous pregnancies this is not associated with counterbalancing upregulation of complement regulatory proteins. Furthermore, C4d deposition in OD pregnancies is not related to the severity of preeclampsia, suggesting another trigger or regulatory mechanism of placental C4d deposition in preeclamptic OD pregnancies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Autologous tenocyte therapy for experimental Achilles tendinopathy in a rabbit model.

    Science.gov (United States)

    Chen, Jimin; Yu, Qian; Wu, Bing; Lin, Zhen; Pavlos, Nathan J; Xu, Jiake; Ouyang, Hongwei; Wang, Allan; Zheng, Ming H

    2011-08-01

    Tendinopathy of the Achilles tendon is a chronic degenerative condition that frequently does not respond to treatment. In the current study, we propose that autologous tenocytes therapy (ATT) is effective in treating tendon degeneration in a collagenase-induced rabbit Achilles tendinopathy model. Chronic tendinopathy was created in the left Achilles tendon of 44 rabbits by an intratendonous injection of type I collagenase. Forty-two rabbits were randomly allocated into three groups of 14 and received control treatment; autologous tenocytes digested from tendon tissue; and autologous tenocytes digested from epitendineum tissue. For cell tracking in vivo, the remaining two animals were injected with autologous tenocytes labeled with a nano-scale super-paramagnetic iron oxide (Feridex). Rabbits were sacrificed at 4 and 8 weeks after the therapeutic injection, and tendon tissue was analyzed by histology, immunostaining, and biomechanical testing to evaluate tissue repair. Autologous tenocyte treatment improved tendon remodeling, histological outcomes, collagen content, and tensile strength of tendinopathic Achilles tendons. Injected tenocytes were integrated into tendon matrix and could be tracked up to 8 weeks in vivo. Immunohistochemistry showed that ATT improved type I collagen expression in repaired tendon but did not affect type III collagen and secreted protein, acidic and rich in cysteine expression. ATT may be a useful treatment of chronic Achilles tendinopathy.

  4. Rejuvenation of the periorbital complex with autologous fat transfer: current therapy.

    Science.gov (United States)

    Ciuci, Paul M; Obagi, Suzan

    2008-08-01

    This article examines the pathophysiology of periorbital aging and details a technique, autologous fat transfer, to restore a youthful appearance to the periorbital complex. The use of photographs taken of patients in their late teens or early 20s shows that the main changes of periorbital aging are consistent with volume loss more so than gravitational changes. This article reflects on the shortcomings of currently accepted surgical approaches to the rejuvenation of the periorbital region. After a detailed clinical evaluation of the periorbital region including overall facial aging, brow position, and eyelid laxity, patients underwent autologous fat transfer to the periorbital region. The technique consists of autologous fat harvesting using the senior author's modification of the Coleman technique to the upper brow and lower eyelid region. Detailed clinical evaluations of each subject, and comparisons to a preoperative youthful photograph of each, were made at 1 week, 6 weeks, and 6 months postoperatively. These evaluations included subjective clinical estimations of overall brow fullness, brow position, and upper and lower eyelid laxity; a judgment of the appearance of the supraorbital and infraorbital rim; appearance of a short lower eyelid length, and an assessment of the subject's convex facial profile. While maintaining a natural, "nonsurgical" appearance with this approach and this technique, the patient achieved a more youthful look after autologous fat transfer. Although there are still indications for brow lift and blepharoplasty in certain patients, neither procedure restores a youthful, rejuvenated appearance to the periorbital complex as well as autologous fat transfer.

  5. Autologous fibrin sealant (Vivostat®) in the neurosurgical practice: Part I: Intracranial surgical procedure

    Science.gov (United States)

    Graziano, Francesca; Certo, Francesco; Basile, Luigi; Maugeri, Rosario; Grasso, Giovanni; Meccio, Flavia; Ganau, Mario; Iacopino, Domenico G.

    2015-01-01

    Background: Hemorrhages, cerebrospinal fluid (CSF) fistula and infections are the most challenging postoperative complications in Neurosurgery. In this study, we report our preliminary results using a fully autologous fibrin sealant agent, the Vivostat® system, in achieving hemostasis and CSF leakage repair during cranio-cerebral procedures. Methods: From January 2012 to March 2014, 77 patients were studied prospectively and data were collected and analyzed. Autologous fibrin sealant, taken from patient's blood, was prepared with the Vivostat® system and applied on the resection bed or above the dura mater to achieve hemostasis and dural sealing. The surgical technique, time to bleeding control and associated complications were recorded. Results: A total of 79 neurosurgical procedures have been performed on 77 patients. In the majority of cases (98%) the same autologous fibrin glue provided rapid hemostasis and dural sealing. No patient developed allergic reactions or systemic complications in association with its application. There were no cases of cerebral hematoma, swelling, infection, or epileptic seizures after surgery whether in the immediate or in late period follow-up. Conclusions: In this preliminary study, the easy and direct application of autologous fibrin sealant agent helped in controlling cerebral bleeding and in providing prompt and efficient dural sealing with resolution of CSF leaks. Although the use of autologous fibrin glue seems to be safe, easy, and effective, further investigations are strongly recommended to quantify real advantages and potential limitations. PMID:25984391

  6. Qualitative assessment of blood washing with the continuous autologous transfusion system (CATS)

    Science.gov (United States)

    Walpoth, B H; Eggensperger, N; Walpoth-Aslan, B N; Neidhart, P; Lanz, M; Zehnder, R; Spaeth, P J; Kurt, G; Althaus, U

    1997-04-01

    A number of different blood-processing methods can be used at the end of cardiopulmonary bypass (CPB) to improve the quality of autologous blood. They include centrifugation, hemofiltration and cell-washing. They differ in processing time required, cost of disposables and the quality of the processed autologous blood product. The newly developed continuous auto-transfusion system (CATS: Fresenius AG, Bad Homburg) uses a continuous cell-washing method. In a prospective study, the oxygenator blood of 10 patients was processed at the end of cardiac surgery with CATS and the quality of autologous blood before and after processing was compared. The processing volumes and the time required were recorded. The concentrations and elimination rates of blood parameters and waste products such as activated coagulation and complement products were measured. At the end of CPB a mean volume of 1,010 +/- 174 ml diluted oxygenator blood was processed and concentrated to 310 +/- 88 ml in 11.0 +/- 2.2 mins. Cellular elements such as erythrocytes and leucocytes were mostly retained and their concentration showed a significant increase after processing (250% and 210% respectively; p plasma proteins. Likewise, all water soluble elements such as waste products are significantly lower in concentration after processing and, if calculated by quantity, they show a high elimination rate (> 93%). In conclusion, the continuous autologous transfusion system permits an automated, rapid and continuous processing of autologous blood yielding a standardised high quality erythrocyte concentrate.

  7. Molecular Mechanisms Modulating the Phenotype of Macrophages and Microglia

    Directory of Open Access Journals (Sweden)

    Stephanie A. Amici

    2017-11-01

    Full Text Available Macrophages and microglia play crucial roles during central nervous system development, homeostasis and acute events such as infection or injury. The diverse functions of tissue macrophages and microglia are mirrored by equally diverse phenotypes. A model of inflammatory/M1 versus a resolution phase/M2 macrophages has been widely used. However, the complexity of macrophage function can only be achieved by the existence of varied, plastic and tridimensional macrophage phenotypes. Understanding how tissue macrophages integrate environmental signals via molecular programs to define pathogen/injury inflammatory responses provides an opportunity to better understand the multilayered nature of macrophages, as well as target and modulate cellular programs to control excessive inflammation. This is particularly important in MS and other neuroinflammatory diseases, where chronic inflammatory macrophage and microglial responses may contribute to pathology. Here, we perform a comprehensive review of our current understanding of how molecular pathways modulate tissue macrophage phenotype, covering both classic pathways and the emerging role of microRNAs, receptor-tyrosine kinases and metabolism in macrophage phenotype. In addition, we discuss pathway parallels in microglia, novel markers helpful in the identification of peripheral macrophages versus microglia and markers linked to their phenotype.

  8. The macrophage in HIV-1 infection: From activation to deactivation?

    Directory of Open Access Journals (Sweden)

    Varin Audrey

    2010-04-01

    Full Text Available Abstract Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1 induced in particular by IFN-γ display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2 induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM. Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease.

  9. Aging and cancer: The role of macrophages and neutrophils.

    Science.gov (United States)

    Jackaman, Connie; Tomay, Federica; Duong, Lelinh; Abdol Razak, Norbaini Bintu; Pixley, Fiona J; Metharom, Pat; Nelson, Delia J

    2017-07-01

    Impaired immune function has been implicated in the declining health and higher incidence of cancer in the elderly. However, age-related changes to immunity are not completely understood. Neutrophils and macrophages represent the first line of defence yet their ability to phagocytose pathogens decrease with aging. Cytotoxic T lymphocytes are critical in eliminating tumors, but T cell function is also compromised with aging. T cell responses can be regulated by macrophages and may depend on the functional phenotype macrophages adopt in response to microenvironmental signals. This can range from pro-inflammatory, anti-tumorigenic M1 to anti-inflammatory, pro-tumorigenic M2 macrophages. Macrophages in healthy elderly adipose and hepatic tissue exhibit a more pro-inflammatory M1 phenotype compared to young hosts whilst immunosuppressive M2 macrophages increase in elderly lymphoid tissues, lung and muscle. These M2-like macrophages demonstrate altered responses to stimuli. Recent studies suggest that neutrophils also regulate T cell function and, like macrophages, neutrophil function is modulated with aging. It is possible that age-modified tissue-specific macrophages and neutrophils contribute to chronic low-grade inflammation that is associated with dysregulated macrophage-mediated immunosuppression, which together are responsible for development of multiple pathologies, including cancer. This review discusses recent advances in macrophage and neutrophil biology in healthy aging and cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Macrophage Polarization in Chronic Inflammatory Diseases: Killers or Builders?

    Directory of Open Access Journals (Sweden)

    Luca Parisi

    2018-01-01

    Full Text Available Macrophages are key cellular components of the innate immunity, acting as the main player in the first-line defence against the pathogens and modulating homeostatic and inflammatory responses. Plasticity is a major feature of macrophages resulting in extreme heterogeneity both in normal and in pathological conditions. Macrophages are not homogenous, and they are generally categorized into two broad but distinct subsets as either classically activated (M1 or alternatively activated (M2. However, macrophages represent a continuum of highly plastic effector cells, resembling a spectrum of diverse phenotype states. Induction of specific macrophage functions is closely related to the surrounding environment that acts as a relevant orchestrator of macrophage functions. This phenomenon, termed polarization, results from cell/cell, cell/molecule interaction, governing macrophage functionality within the hosting tissues. Here, we summarized relevant cellular and molecular mechanisms driving macrophage polarization in “distant” pathological conditions, such as cancer, type 2 diabetes, atherosclerosis, and periodontitis that share macrophage-driven inflammation as a key feature, playing their dual role as killers (M1-like and/or builders (M2-like. We also dissect the physio/pathological consequences related to macrophage polarization within selected chronic inflammatory diseases, placing polarized macrophages as a relevant hallmark, putative biomarkers, and possible target for prevention/therapy.

  11. Drug Trafficking into Macrophages via the Endocytotic Receptor CD163.

    Science.gov (United States)

    Graversen, Jonas Heilskov; Moestrup, Søren Kragh

    2015-06-23

    In inflammatory diseases, macrophages are a main producer of a range of cytokines regulating the inflammatory state. This also includes inflammation induced by tumor growth, which recruits so-called tumor-associated macrophages supporting tumor growth. Macrophages are therefore relevant targets for cytotoxic or phenotype-modulating drugs in the treatment of inflammatory and cancerous diseases. Such targeting of macrophages has been tried using the natural propensity of macrophages to non-specifically phagocytose circulating foreign particulate material. In addition, the specific targeting of macrophage-expressed receptors has been used in order to obtain a selective uptake in macrophages and reduce adverse effects of off-target delivery of drugs. CD163 is a highly expressed macrophage-specific endocytic receptor that has been studied for intracellular delivery of small molecule drugs to macrophages using targeted liposomes or antibody drug conjugates. This review will focus on the biology of CD163 and its potential role as a target for selective macrophage targeting compared with other macrophage targeting approaches.

  12. Influenza virus replication in macrophages: balancing protection and pathogenesis.

    Science.gov (United States)

    Cline, Troy D; Beck, Donald; Bianchini, Elizabeth

    2017-10-01

    Macrophages are essential for protection against influenza A virus infection, but are also implicated in the morbidity and mortality associated with severe influenza disease, particularly during infection with highly pathogenic avian influenza (HPAI) H5N1 virus. While influenza virus infection of macrophages was once thought to be abortive, it is now clear that certain virus strains can replicate productively in macrophages. This may have important consequences for the antiviral functions of macrophages, the course of disease and the outcome of infection for the host. In this article, we review findings related to influenza virus replication in macrophages and the impact of productive replication on macrophage antiviral functions. A clear understanding of the interactions between influenza viruses and macrophages may lead to new antiviral therapies to relieve the burden of severe disease associated with influenza viruses.

  13. Macrophage activation and polarization: nomenclature and experimental guidelines.

    Science.gov (United States)

    Murray, Peter J; Allen, Judith E; Biswas, Subhra K; Fisher, Edward A; Gilroy, Derek W; Goerdt, Sergij; Gordon, Siamon; Hamilton, John A; Ivashkiv, Lionel B; Lawrence, Toby; Locati, Massimo; Mantovani, Alberto; Martinez, Fernando O; Mege, Jean-Louis; Mosser, David M; Natoli, Gioacchino; Saeij, Jeroen P; Schultze, Joachim L; Shirey, Kari Ann; Sica, Antonio; Suttles, Jill; Udalova, Irina; van Ginderachter, Jo A; Vogel, Stefanie N; Wynn, Thomas A

    2014-07-17

    Description of macrophage activation is currently contentious and confusing. Like the biblical Tower of Babel, macrophage activation encompasses a panoply of descriptors used in different ways. The lack of consensus on how to define macrophage activation in experiments in vitro and in vivo impedes progress in multiple ways, including the fact that many researchers still consider there to be only two types of activated macrophages, often termed M1 and M2. Here, we describe a set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation-with the goal of unifying experimental standards for diverse experimental scenarios. Collectively, we propose a common framework for macrophage-activation nomenclature. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. HIV Infection of Macrophages: Implications for Pathogenesis and Cure

    Directory of Open Access Journals (Sweden)

    Kiera Leigh Clayton

    2017-05-01

    Full Text Available Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

  15. Regeneration of Tissues and Organs Using Autologous Cells

    Energy Technology Data Exchange (ETDEWEB)

    Anthony Atala, M D

    2012-10-11

    The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat

  16. Autologous Intravenous Mononuclear Stem Cell Therapy in Chronic Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Bhasin A

    2012-01-01

    Full Text Available Background: The regenerative potential of brain has led to emerging therapies that can cure clinico-motor deficits after neurological diseases. Bone marrow mononuclear cell therapy is a great hope to mankind as these cells are feasible, multipotent and aid in neurofunctional gains in Stroke patients. Aims: This study evaluates safety, feasibility and efficacy of autologous mononuclear (MNC stem cell transplantation in patients with chronic ischemic stroke (CIS using clinical scores and functional imaging (fMRI and DTI. Design: Non randomised controlled observational study Study: Twenty four (n=24 CIS patients were recruited with the inclusion criteria as: 3 months–2years of stroke onset, hand muscle power (MRC grade at least 2; Brunnstrom stage of recovery: II-IV; NIHSS of 4-15, comprehendible. Fugl Meyer, modified Barthel Index (mBI and functional imaging parameters were used for assessment at baseline, 8 weeks and at 24 weeks. Twelve patients were administered with mean 54.6 million cells intravenously followed by 8 weeks of physiotherapy. Twelve patients served as controls. All patients were followed up at 24 weeks. Outcomes: The laboratory and radiological outcome measures were within normal limits in MNC group. Only mBI showed statistically significant improvement at 24 weeks (p<0.05 whereas the mean FM, MRC, Ashworth tone scores in the MNC group were high as compared to control group. There was an increased number of cluster activation of Brodmann areas BA 4, BA 6 post stem cell infusion compared to controls indicating neural plasticity. Cell therapy is safe and feasible which may facilitate restoration of function in CIS.

  17. Arthroscopic autologous chondrocyte implantation in the ankle joint.

    Science.gov (United States)

    Giannini, Sandro; Buda, Roberto; Ruffilli, Alberto; Cavallo, Marco; Pagliazzi, Gherardo; Bulzamini, Maria Chiara; Desando, Giovanna; Luciani, Deianira; Vannini, Francesca

    2014-06-01

    Autologous chondrocyte implantation (ACI) is an established procedure in the ankle providing satisfactory results. The development of a completely arthroscopic ACI procedure in the ankle joint made the technique easier and reduced the morbidity. The purpose of this investigation was to report the clinical results of a series of patients who underwent arthroscopic ACI of the talus at a mean of 7 ± 1.2-year follow-up. Forty-six patients (mean age 31.4 ± 7.6) affected by osteochondral lesions of the talar dome (OLT) received arthroscopic ACI between 2001 and 2006. Patients were clinically evaluated using AOFAS score pre-operatively and at 12, 36 months and at final follow-up of 87.2 ± 14.5 months. The mean pre-operative AOFAS score was 57.2 ± 14.3. At the 12-month follow-up, the mean AOFAS score was 86.8 ± 13.4 (p = 0.0005); at 36 months after surgery, the mean score was 89.5 ± 13.4 (p = 0.0005); whereas at final follow-up of 87.2 ± 14.5 months it was 92.0 ± 11.2 (p = 0.0005). There were three failures. Histological and immunohistochemical evaluations of specimens harvested from failed implants generally showed several aspects of a fibro-cartilaginous tissue associated with some aspects of cartilage tissue remodelling as indicated by the presence of type II collagen expression. This study confirmed the ability of arthroscopic ACI to repair osteochondral lesions in the ankle joint with satisfactory clinical results after mid-term follow-up. IV, retrospective case series.

  18. Contralateral Autologous Corneal Transplantation Experience in Mexico City.

    Science.gov (United States)

    Perez-Balbuena, Ana L; Ancona-Lezama, David; Delgado-Pelayo, Sarai; Martinez, Jaime D

    2017-01-01

    The aim of this study is to expand the limited knowledge regarding autologous contralateral penetrating keratoplasty. We report the retrospective outcomes of patients who received autokeratoplasty and contralateral opaque corneas in the donor eye at a tertiary care ophthalmology hospital in Mexico City. Eleven patients received autokeratoplasty and contralateral opaque corneas in the donor eye at our center from 2010 to 2015. The mean patient age at the time of surgery was 58 years (range, 35-85 yrs), with 4 female and 7 male patients. There were no surgical or immediate postsurgical complications in the autokeratoplasty eye. However, 1 patient had expulsive hemorrhage in the sightless eye. Follow-up duration ranged from 11 to 65 months (mean, 26 mo). During follow-up, 3 of the autokeratoplasty procedures failed because of endothelial attenuation. Identified known risk factors for failure of the eye with visual potential included the presence of an Ahmed glaucoma drainage device in 7/11 patients (63%), history of glaucoma in 8/11 (72%), past heterologous penetrating keratoplasty in 2/11 (18%), Vogt-Koyanagi-Harada syndrome in 1/11 (9%), and 4-quadrant corneal vascularization in 1/11 (9%). Autokeratoplasty is a good choice in cases having high risk factors and when fresh corneal tissue is not available. This is the largest study describing outcomes of patients who underwent autokeratoplasty. This technique offers no risk of immune rejection and no need for immunosuppression treatment. This study reports a good prognosis in cases having high risk factors for failure.

  19. Cost analysis and quality of life assessment comparing patients undergoing autologous peripheral blood stem cell transplantation or autologous bone marrow transplantation for refractory or relapsed non-Hodgkin's lymphoma or Hodgkin's disease : a prospective randomised trial

    NARCIS (Netherlands)

    van Agthoven, M; Vellenga, E; Fibbe, WE; Kingma, T; Uyl-de Groot, CA

    The cost-effectiveness of autologous peripheral blood stem cell transplantation (PBSCT) compared with autologous bone marrow transplantation (ABMT) for refractory or relapsed non-Hodgkin's lymphoma (NHL) or Morbus Hodgkin (MH) was assessed. Costs were determined from the induction chemotherapy

  20. Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis. Mice deficient in Rac2 were protected against bleomycin-induced fibrosis and displayed diminished collagen deposition in association with lower expression of alternatively activated profibrotic macrophage markers. We have demonstrated a macrophage autonomous process by which the injection of M2 and not M1 macrophages restored the bleomycin induced pulmonary fibrosis susceptibility in Rac2-/- mice, establishing a critical role for a macrophage Rac2 signaling axis in the regulation of macrophage differentiation and lung fibrosis in vivo. We also demonstrate that markers of alternative macrophage activation are increased in patients with IPF. Taken together, these studies define an important role for an integrin-driven Rac2 signaling axis in macrophages, and reveal that Rac2 activation is required for polarization of macrophages towards a profibrotic phenotype and progression of pulmonary fibrosis in vivo.

  1. Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype

    Science.gov (United States)

    Zulcic, Muamera; Jiang, Min; Pardo, Annie; Selman, Moises; Hagood, James S.

    2017-01-01

    Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by cellular phenotype alterations and deposition of extracellular matrix proteins. The alternative activation of macrophages in the lungs has been associated as a major factor promoting pulmonary fibrosis, however the mechanisms underlying this phenomenon are poorly understood. In the present study, we have defined a molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin lead to the activation of Rac2 which regulates alternative macrophage differentiation, a signaling axis within the pulmonary macrophage compartment required for bleomycin induced pulmonary fibrosis. Mice deficient in Rac2 were protected against bleomycin-induced fibrosis and displayed diminished collagen deposition in association with lower expression of alternatively activated profibrotic macrophage markers. We have demonstrated a macrophage autonomous process by which the injection of M2 and not M1 macrophages restored the bleomycin induced pulmonary fibrosis susceptibility in Rac2-/- mice, establishing a critical role for a macrophage Rac2 signaling axis in the regulation of macrophage differentiation and lung fibrosis in vivo. We also demonstrate that markers of alternative macrophage activation are increased in patients with IPF. Taken together, these studies define an important role for an integrin-driven Rac2 signaling axis in macrophages, and reveal that Rac2 activation is required for polarization of macrophages towards a profibrotic phenotype and progression of pulmonary fibrosis in vivo. PMID:28817691

  2. Detecting autologous blood transfusions: a comparison of three passport approaches and four blood markers

    DEFF Research Database (Denmark)

    Mørkeberg, J; Sharpe, K; Belhage, B

    2011-01-01

    Blood passport has been suggested as an indirect tool to detect various kinds of blood manipulations. Autologous blood transfusions are currently undetectable, and the objective of this study was to examine the sensitivities of different blood markers and blood passport approaches in order...... to determine the best approach to detect autologous blood transfusions. Twenty-nine subjects were transfused with either one (n=8) or three (n=21) bags of autologous blood. Hemoglobin concentration ([Hb]), percentage of reticulocytes (%ret) and hemoglobin mass (Hbmass) were measured 1 day before reinfusion...... and six times after reinfusion. The sensitivity and specificity of a novel marker, Hbmr (based on Hbmass and %ret), was evaluated together with [Hb], Hbmass and OFF-hr by different passport methods. Our novel Hbmr marker showed superior sensitivity in detecting the highest dosage of transfused blood...

  3. Gastrocnemius tendon strain in a dog treated with autologous mesenchymal stem cells and a custom orthosis.

    Science.gov (United States)

    Case, J Brad; Palmer, Ross; Valdes-Martinez, Alex; Egger, Erick L; Haussler, Kevin K

    2013-05-01

    To report clinical findings and outcome in a dog with gastrocnemius tendon strain treated with autologous mesenchymal stem cells and a custom orthosis. Clinical report. A 4-year-old spayed female Border Collie. Bone-marrow derived, autologous mesenchymal stem cells were transplanted into the tendon core lesion. A custom, progressive, dynamic orthosis was fit to the tarsus. Serial orthopedic examinations and ultrasonography as well as long-term force-plate gait analysis were utilized for follow up. Lameness subjectively resolved and peak vertical force increased from 43% to 92% of the contralateral pelvic limb. Serial ultrasonographic examinations revealed improved but incomplete restoration of normal linear fiber pattern of the gastrocnemius tendon. Findings suggest that autologous mesenchymal stem cell transplantation with custom, progressive, dynamic orthosis may be a viable, minimally invasive technique for treatment of calcaneal tendon injuries in dogs. © Copyright 2013 by The American College of Veterinary Surgeons.

  4. Autologous Fat Grafting as a Novel Approach to Parastomal Soft-tissue Volume Deficiencies

    Directory of Open Access Journals (Sweden)

    Robert C. Wu, MD

    2014-03-01

    Full Text Available Summary: The aim of this study is to describe a novel approach to revise maladaptive soft-tissue contour around an ileostomy. A patient with permanent ileostomy suffered from significant defects in soft-tissue contour due to scarring and wound contraction. He underwent autologous fat grafting to achieve sealing of his stoma appliance and improve cosmesis. Due to numerous surgeries, the stoma appliance would not seal and required daily appliance changes. The patient received autologous fat grafting to augment the contour around stoma. A complete fitting of stoma was achieved. The patient is satisfied with stoma sealing and is changing his stoma appliance every 5–7 days without skin excoriation. Autologous fat transfer is an effective approach to treat a subset of stoma patients with complex subcutaneous defects.

  5. Enrichment of autologous fat grafts with ex-vivo expanded adipose tissue-derived stem cells for graft survival

    DEFF Research Database (Denmark)

    Kølle, Stig-Frederik Trojahn; Fischer-Nielsen, Anne; Mathiasen, Anders Bruun

    2013-01-01

    Autologous fat grafting is increasingly used in reconstructive surgery. However, resorption rates ranging from 25% to 80% have been reported. Therefore, methods to increase graft viability are needed. Here, we report the results of a triple-blind, placebo-controlled trial to compare the survival ...... of fat grafts enriched with autologous adipose-derived stem cells (ASCs) versus non-enriched fat grafts....

  6. Is there evidence that barrier membranes prevent bone resorption in autologous bone grafts during the healing period? A systematic review

    NARCIS (Netherlands)

    Gielkens, Pepijn F. M.; Bos, Ruud R. M.; Raghoebar, Gerry M.; Stegenga, Boudewijn

    2007-01-01

    Introduction: Autologous bone is considered the "reference standard" for bone-grafting procedures. A barrier membrane covering an autologous bone graft (guided bone regeneration [GBR]) is expected to prevent graft resorption. Good clinical results have been reported for GBR, although potential

  7. Loss of quiescence and impaired function of CD34(+)/CD38(low) cells one year following autologous stem cell transplantation

    NARCIS (Netherlands)

    Woolthuis, Carolien M.; Brouwers-Vos, Annet Z.; Huls, Gerwin; de Wolf, Joost Th. M.; Schuringa, Jan Jacob; Vellenga, Edo

    2013-01-01

    Patients who have undergone autologous stem cell transplantation are subsequently more susceptible to chemotherapy-induced bone marrow toxicity. In the present study, bone marrow primitive progenitor cells were examined one year after autologous stem cell transplantation and compared with normal

  8. Autologous Chondrocyte Implantation "Sandwich" Technique Compared With Autologous Bone Grafting for Deep Osteochondral Lesions in the Knee.

    Science.gov (United States)

    Minas, Tom; Ogura, Takahiro; Headrick, Jeff; Bryant, Tim

    2018-02-01

    Treating symptomatic osteochondral defects is challenging, especially in young adults with deep (>8-10 mm) empty defects after osteochondritis dissecans (OCD) or collapsed condyles secondary to avascular necrosis (AVN). For this population, osteoarthritis (OA) is inevitable if articular congruence is not restored. To describe the autologous chondrocyte implantation (ACI) "sandwich" technique with autologous bone grafting (ABG) and compare it with ABG alone for restoration of the osteochondral unit. The midterm to long-term outcomes in patients after the treatment for OCD and AVN will be reported and compared. Cohort study; Level of evidence, 3. The outcomes for a consecutive cohort of 24 patients who underwent combined ABG with the ACI sandwich technique between 2001 and 2013 (ACI sandwich group) was compared with a historical control group of 17 consecutive patients who underwent ABG alone between 1995 and 2002 (ABG group) by a single surgeon for symptomatic deep (>8 mm) osteochondral lesions. Patients who were followed up with a minimum of 2 years were included in this study. The modified Cincinnati Knee Rating System, the Western Ontario and McMaster Universities Osteoarthritis Index, a visual analog scale (VAS), the Short Form-36, and a patient satisfaction survey were used to evaluate clinical outcomes. Survival analysis was performed using the Kaplan-Meier method, with no clinical improvement, graft failure, or conversion to prosthetic arthroplasty as the endpoint (failure). Kellgren-Lawrence (K-L) grading to assess OA progression was also performed. In the ABG group, 13 of 17 patients (76%) were available with a mean follow-up of 15.7 years postoperatively (range, 5-21 years). In the ACI sandwich group, all 24 patients were available with a mean follow-up of 7.8 years postoperatively (range, 2-15 years). No significant differences were observed between the groups in terms of age, sex, side of the operated knee, body mass index, lesion type, lesion size

  9. Survival and regeneration of deep-freeze preserved autologous cranial bones after cranioplasty.

    Science.gov (United States)

    Lu, Yi; Hui, Guozhen; Liu, Fengqiang; Wang, Zhengan; Tang, Yuming; Gao, Shuxing

    2012-04-01

    After decompressive craniectomy, a deep-freeze-preserved autologous cranial bone graft can be used for cranioplasty to avoid immunoreaction against an artificial patch material. Autologous cranial bone grafts not only have better physical properties, such as heat conduction, compared to artificial patch materials, but they also have the advantages of a lower medical cost and satisfactory physical flexibility. The discussion over (99)Tc(m)-MDP SPECT static cranial bone tomography in the diagnosis of survival and regeneration in deep-freeze preservation autologous cranial bones after cranioplasty is valuable. Objective. To investigate whether deep-freeze-preserved autologous cranial bone grafts could survive and regenerate after autologous reimplantation. The method of cranial bone preservation involved removing the cranial graft and sealing it in a double-layer sterile plastic bag under sterile surgical conditions. On the day of the cranioplasty operation, the cranial bone graft was disinfected by immersing it in 3% povidone-iodine for 30 minutes. At short-term (2 weeks), medium-term (3 months), and long-term (12 months) postoperative follow-up visits, (99)Tc(m)-MDP SPECT static cranial bone tomography was used to examine the reimplanted cranial bone. Results. There were no postoperative infections or seromas in all 16 cases. Two weeks following cranial bone graft reimplantation, the SPECT tomography showed some radioactivity uptake in the reimplanted cranial bone graft, which was lower than that in the cranial bone on the healthy side. At 3 months and 12 months after the operation, the radioactivity uptake in the reimplanted cranial bone graft was the same as that in the cranial bone on the healthy side. X-ray films showed blurred sutures in the reimplanted cranial bone graft at 12 months after surgery. Reimplanted deep-freeze-preserved autologous cranial bone can survive in the short term and regenerate in the medium and long terms.

  10. Phenotype and polarization of autologous T cells by biomaterial-treated dendritic cells.

    Science.gov (United States)

    Park, Jaehyung; Gerber, Michael H; Babensee, Julia E

    2015-01-01

    Given the central role of dendritic cells (DCs) in directing T-cell phenotypes, the ability of biomaterial-treated DCs to dictate autologous T-cell phenotype was investigated. In this study, we demonstrate that differentially biomaterial-treated DCs differentially directed autologous T-cell phenotype and polarization, depending on the biomaterial used to pretreat the DCs. Immature DCs (iDCs) were derived from human peripheral blood monocytes and treated with biomaterial films of alginate, agarose, chitosan, hyaluronic acid, or 75:25 poly(lactic-co-glycolic acid) (PLGA), followed by co-culture of these biomaterial-treated DCs and autologous T cells. When autologous T cells were co-cultured with DCs treated with biomaterial film/antigen (ovalbumin, OVA) combinations, different biomaterial films induced differential levels of T-cell marker (CD4, CD8, CD25, CD69) expression, as well as differential cytokine profiles [interferon (IFN)-γ, interleukin (IL)-12p70, IL-10, IL-4] in the polarization of T helper (Th) types. Dendritic cells treated with agarose films/OVA induced CD4+CD25+FoxP3+ (T regulatory cells) expression, comparable to untreated iDCs, on autologous T cells in the DC-T co-culture system. Furthermore, in this co-culture, agarose treatment induced release of IL-12p70 and IL-10 at higher levels as compared with DC treatment with other biomaterial films/OVA, suggesting Th1 and Th2 polarization, respectively. Dendritic cells treated with PLGA film/OVA treatment induced release of IFN-γ at higher levels compared with that observed for co-cultures with iDCs or DCs treated with all other biomaterial films. These results indicate that DC treatment with different biomaterial films has potential as a tool for immunomodulation by directing autologous T-cell responses. © 2014 Wiley Periodicals, Inc.

  11. Autologous Dendritic Cells Pulsed with Allogeneic Tumor Cell Lysate in Mesothelioma: From Mouse to Human.

    Science.gov (United States)

    Aerts, Joachim G J V; de Goeje, Pauline L; Cornelissen, Robin; Kaijen-Lambers, Margaretha E H; Bezemer, Koen; van der Leest, Cor H; Mahaweni, Niken M; Kunert, André; Eskens, Ferry A L M; Waasdorp, Cynthia; Braakman, Eric; van der Holt, Bronno; Vulto, Arnold G; Hendriks, Rudi W; Hegmans, Joost P J J; Hoogsteden, Henk C

    2018-02-15

    Purpose: Mesothelioma has been regarded as a nonimmunogenic tumor, which is also shown by the low response rates to treatments targeting the PD-1/PD-L1 axis. Previously, we demonstrated that autologous tumor lysate-pulsed dendritic cell (DC) immunotherapy increased T-cell response toward malignant mesothelioma. However, the use of autologous tumor material hampers implementation in large clinical trials, which might be overcome by using allogeneic tumor cell lines as tumor antigen source. The purpose of this study was to investigate whether allogeneic lysate-pulsed DC immunotherapy is effective in mice and safe in humans. Experimental Design: First, in two murine mesothelioma models, mice were treated with autologous DCs pulsed with either autologous or allogeneic tumor lysate or injected with PBS (negative control). Survival and tumor-directed T-cell responses of these mice were monitored. Results were taken forward in a first-in-human clinical trial, in which 9 patients were treated with 10, 25, or 50 million DCs per vaccination. DC vaccination consisted of autologous monocyte-derived DCs pulsed with tumor lysate from five mesothelioma cell lines. Results: In mice, allogeneic lysate-pulsed DC immunotherapy induced tumor-specific T cells and led to an increased survival, to a similar extent as DC immunotherapy with autologous tumor lysate. In the first-in-human clinical trial, no dose-limiting toxicities were established and radiographic responses were observed. Median PFS was 8.8 months [95% confidence interval (CI), 4.1-20.3] and median OS not reached (median follow-up = 22.8 months). Conclusions: DC immunotherapy with allogeneic tumor lysate is effective in mice and safe and feasible in humans. Clin Cancer Res; 24(4); 766-76. ©2017 AACR . ©2017 American Association for Cancer Research.

  12. Macrophagic myofasciitis and vaccination: consequence or coincidence?

    Science.gov (United States)

    Santiago, Tânia; Rebelo, Olinda; Negrão, Luís; Matos, Anabela

    2015-01-01

    Macrophagic myofasciitis (MMF) characterized by specific muscle lesions assessing long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization has been reported with increasing frequency in the past 10 years. We describe clinical and laboratory findings in patients with MMF. We did a retrospective analysis of 16 cases observed in our Neuropathology Laboratory, between January 2000 and July 2013. The mean age of the 16 patients was 48.8 ± 18.0 years; 80.0 % were female. Chronic fatigue syndrome was found in 8 of 16 patients. Half of the patients had elevated creatinine kinase levels, and 25.0 % had a myopathic electromyogram. Thirteen patients received intramuscular administration of aluminum-containing vaccine prior to the onset of symptoms. MMF may mirror a distinctive pattern of an inflammatory myopathy. The vaccines containing this adjuvant may trigger MMF in some patients.

  13. Metabolic Modulation in Macrophage Effector Function

    Directory of Open Access Journals (Sweden)

    Ciana Diskin

    2018-02-01

    Full Text Available Traditionally cellular respiration or metabolism has been viewed as catabolic and anabolic pathways generating energy and biosynthetic precursors required for growth and general cellular maintenance. However, growing literature provides evidence of a much broader role for metabolic reactions and processes in controlling immunological effector functions. Much of this research into immunometabolism has focused on macrophages, cells that are central in pro- as well as anti-inflammatory responses—responses that in turn are a direct result of metabolic reprogramming. As we learn more about the precise role of metabolic pathways and pathway intermediates in immune function, a novel opportunity to target immunometabolism therapeutically has emerged. Here, we review the current understanding of the regulation of macrophage function through metabolic remodeling.

  14. Macrophage specific drug delivery in experimental leishmaniasis.

    Science.gov (United States)

    Basu, Mukul Kumar; Lala, Sanchaita

    2004-09-01

    Macrophage-specific delivery systems are the subject of much interest nowadays, because of the fact that macrophages act as host cells for many parasites and bacteria, which give rise to outbreak of so many deadly diseases(eg. leishmaniasis, tuberculosis etc.) in humans. To combat these deadly diseases initially macrophage specific liposomal delivery system were thought of and tested in vivo against experimental leishmaniasis in hamsters using a series of indigenous or synthetic antileishmanial compounds and the results were critically discussed. In vitro testing was also done against macrophages infected with Leishmania donovani, the causative agent for visceral leishmaniasis. The common problem of liposome therapy being their larger size, stability and storage, non-ionic surfactant vesicles, niosomes were prepared, for their different drug distribution and release characteristics compared to liposomes. When tested in vivo, the retention capacity of niosomes was found to be higher than that of liposomes due to the absence of lipid molecules and their smaller size. Thus the therapeutic efficacy of certain antileishmanial compounds was found to be better than that in the liposomal form. The niosomes, being cheaper, less toxic, biodegradable and non-immunogenic, were considered for sometime as suitable alternatives to liposomes as drug carriers. Besides the advent of other classical drugs carriers(e.g. neoglycoproteins), the biggest challenge came from polymeric delivery vehicles, specially the polymeric nanoparticles which were made of cost effective biodegradable polymers and different natural polymers. Because of very small size and highly stable nature, use of nanoparticles as effective drug carriers has been explored in experimental leishmaniasis using a series of antileishmanial compounds, both of indigenous and synthetic origin. The feasibility of application in vivo, when tested for biological as well as for other physicochemical parameters, the polymeric

  15. Human Induced Pluripotent Stem Cell-Derived Macrophages for Unraveling Human Macrophage Biology.

    Science.gov (United States)

    Zhang, Hanrui; Reilly, Muredach P

    2017-11-01

    Despite a substantial appreciation for the critical role of macrophages in cardiometabolic diseases, understanding of human macrophage biology has been hampered by the lack of reliable and scalable models for cellular and genetic studies. Human induced pluripotent stem cell (iPSC)-derived macrophages (IPSDM), as an unlimited source of subject genotype-specific cells, will undoubtedly play an important role in advancing our understanding of the role of macrophages in human diseases. In this review, we summarize current literature in the differentiation and characterization of IPSDM at phenotypic, functional, and transcriptomic levels. We emphasize the progress in differentiating iPSC to tissue resident macrophages, and in understanding the ontogeny of in vitro differentiated IPSDM that resembles primitive hematopoiesis, rather than adult definitive hematopoiesis. We review the application of IPSDM in modeling both Mendelian genetic disorders and host-pathogen interactions. Finally, we highlighted the potential areas of research using IPSDM in functional validation of coronary artery disease loci in genome-wide association studies, functional genomic analyses, drug testing, and cell therapeutics in cardiovascular diseases. © 2017 American Heart Association, Inc.

  16. Fresh mouse peritoneal macrophages have low scavenger receptor activity.

    Science.gov (United States)

    Kim, J G; Keshava, C; Murphy, A A; Pitas, R E; Parthasarathy, S

    1997-11-01

    Peritoneal macrophages are easily isolated by lavage, suggesting that they are either nonadherent or weakly adherent in situ. Cultured macrophages express class A scavenger receptors (SCR), which mediate Ca2+-independent adhesion in vitro. We examined fresh peritoneal macrophages from mice and from women with endometriosis to determine whether the adherence of these cells was associated with increased expression of class A SCR. Fresh human macrophages were not immunoreactive to SCR antibodies; however, SCR immunoreactivity increased with time in culture. Fresh mouse and human macrophages took up minimal amounts of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI)-acetyl-low density lipoproteins (Ac-LDL), a class A SCR ligand. Murine macrophages in culture for 24-72 h internalized four times more Ac-LDL than fresh cells. Cells cultured for 2 days incorporated 3.2 times more [14C] oleate than freshly isolated cells (55.7 +/- 7.9 versus 17.6 +/- 3.0 nmol/mg cell protein). In contrast to SCR activity, mouse macrophage SCR mRNA expression was similar in freshly isolated macrophages and those cultured for 3 days. These results suggest that peritoneal macrophages express only low levels of SCR activity in situ and that posttranscriptional regulation after isolation leads to an increase in SCR activity that correlates with adherence of the macrophages in vitro.

  17. ACAT1 deficiency increases cholesterol synthesis in mouse peritoneal macrophages.

    Science.gov (United States)

    Dove, Dwayne E; Su, Yan Ru; Swift, Larry L; Linton, MacRae F; Fazio, Sergio

    2006-06-01

    Acyl-coenzyme A:cholesterol acyltransferase (ACAT) esterifies free cholesterol and stores cholesteryl esters in lipid droplets. Macrophage ACAT1 deficiency results in increased atherosclerotic lesion area in hyperlipidemic mice via disrupted cholesterol efflux, increased lipoprotein uptake, accumulation of intracellular vesicles, and accelerated apoptosis. The objective of this study was to determine whether lipid synthesis is affected by ACAT1. The synthesis, esterification, and efflux of new cholesterol were measured in peritoneal macrophages from ACAT1(-/-) mice. Cholesterol synthesis was increased by 134% (p=0.001) in ACAT1(-/-) macrophages compared to wildtype macrophages. Increased synthesis resulted in a proportional increase in the efflux of newly synthesized cholesterol. Although the esterification of new cholesterol was reduced by 93% (pSREBP1a mRNA was increased 6-fold in ACAT1(-/-) macrophages compared to wildtype macrophages, suggesting an up-regulation of cholesterol and fatty acid synthesis in ACAT1(-/-) macrophages. Increased cholesterol synthesis and up-regulation of SREBP in ACAT1(-/-) macrophages suggests that ACAT1 affects the regulation of lipid metabolism in macrophages. This change in cholesterol homeostasis may contribute to the atherogenic potential of ACAT1(-/-) macrophages.

  18. Purinergic signaling to terminate TLR responses in macrophages

    Directory of Open Access Journals (Sweden)

    Kajal eHamidzadeh

    2016-03-01

    Full Text Available Macrophages undergo profound physiological alterations when they encounter pathogen associated molecular patterns (PAMPs. These alterations can result in the elaboration of cytokines and mediators that promote immune responses and contribute to the clearance of pathogens. These innate immune responses by myeloid cells are transient. The termination of these secretory responses is not due to the dilution of stimuli, but rather to the active down-regulation of innate responses induced by the very PAMPs that initiated them. Here we describe a purinergic autoregulatory program whereby TLR-stimulated macrophages control their activation state. In this program, TLR stimulated macrophages undergo metabolic alterations that result in the production of ATP and its release through membrane pannexin channels. This purine nucleotide is rapidly hydrolyzed to adenosine by ectoenzymes on the macrophage surface, CD39 and CD73. Adenosine then signals through the P1 class of seven transmembrane receptors to induce a regulatory state that is characterized by the down-regulation of inflammatory cytokines and the production of anti-inflammatory cytokines and growth factors. This purinergic autoregulatory system mitigates the collateral damage that would be caused by the prolonged activation of macrophages, and rather allows the macrophage to maintain homeostasis. The transient activation of macrophages can be prolonged by treating macrophages with IFN-γ. IFN-γ treated macrophages become less sensitive to the regulatory effects of adenosine, allowing them to sustain macrophage activation for the duration of an adaptive immune response.

  19. Metabotropic glutamate receptor 5 may be involved in macrophage plasticity

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    Lali Shanshiashvili

    Full Text Available Abstract Background Macrophages are a functionally heterogeneous cell population and depending on microenvironments they polarize in two main groups: M1 and M2. Glutamic acid and glutamate receptors may participate in the regulation of macrophage plasticity. To investigate the role of glutamatergic systems in macrophages physiology, we performed the transfection of mGluR5 cDNAs into RAW-264.7 cells. Results Comparative analysis of modified (RAW-mGluR5 macrophages and non-modified macrophages (RAW-macrophages has shown that the RAW-mGluR5 macrophages absorbed more glutamate than control cells and the amount of intracellular glutamate correlated with the expression of excitatory amino acid transporters -2 (EAAT-2. Besides, our results have shown that RAW-mGluR5 macrophages expressed a higher level of peroxisome proliferator-activated receptor γ (PPAR-γ and secreted more IL-10, high mobility group box 1 proteins (HMGB1 and Galectin-3 than control RAW-macrophages. Conclusions We propose that elevation of intracellular glutamate and expression of mGluR5 may initiate the metabolic rearrangement in macrophages that could contribute to the formation of an immunosuppressive phenotype.

  20. Successful Treatment of Osgood–Schlatter Disease with Autologous-Conditioned Plasma in Two Patients

    Science.gov (United States)

    Danneberg, Dirk-Jonas

    2017-01-01

    Osgood–Schlatter Disease (OSD) is a painful, growth-related overuse condition of the tibial tuberosity, leading to inflammation of the patellar ligament at the tibial tuberosity. It primarily affects young adolescents, athletic population, and usually, resolves with age or skeletal maturity. Therapy is usually conservative, with surgery indicated in a minority of cases. For patients with treatment-resistant or refractory OSD, an alternative is the application of autologous platelet concentrate. Here, we describe two cases in which autologous-conditioned plasma therapy was used to treat OSD, and present the treatment protocol developed in our clinic. PMID:29270553

  1. Successful Treatment of Osgood-Schlatter Disease with Autologous-Conditioned Plasma in Two Patients.

    Science.gov (United States)

    Danneberg, Dirk-Jonas

    2017-09-01

    Osgood-Schlatter Disease (OSD) is a painful, growth-related overuse condition of the tibial tuberosity, leading to inflammation of the patellar ligament at the tibial tuberosity. It primarily affects young adolescents, athletic population, and usually, resolves with age or skeletal maturity. Therapy is usually conservative, with surgery indicated in a minority of cases. For patients with treatment-resistant or refractory OSD, an alternative is the application of autologous platelet concentrate. Here, we describe two cases in which autologous-conditioned plasma therapy was used to treat OSD, and present the treatment protocol developed in our clinic.

  2. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid

    International Nuclear Information System (INIS)

    Ambrus, C.M.; Ambrus, J.L.

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole-body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colony-forming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls

  3. Chondrocyte-seeded type I/III collagen membrane for autologous chondrocyte transplantation

    DEFF Research Database (Denmark)

    Niemeyer, Philipp; Lenz, Philipp; Kreuz, Peter C

    2010-01-01

    PURPOSE: We report the 2-year clinical results and identify prognostic factors in patients treated with autologous chondrocyte transplantation by use of a collagen membrane to seed the chondrocytes (ACT-CS). METHODS: This is a prospective study of 59 patients who were treated with ACT-CS and foll......PURPOSE: We report the 2-year clinical results and identify prognostic factors in patients treated with autologous chondrocyte transplantation by use of a collagen membrane to seed the chondrocytes (ACT-CS). METHODS: This is a prospective study of 59 patients who were treated with ACT...

  4. Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

    Science.gov (United States)

    Nair, Velu; Sharma, Ajay; Sharma, Sanjeevan; Das, Satyaranjan; Bhakuni, Darshan S; Narayanan, Krishnan; Nair, Vivek; Shankar, Subramanian

    2015-03-01

    Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  5. M2 polarization enhances silica nanoparticle uptake by macrophages

    Directory of Open Access Journals (Sweden)

    Jessica eHoppstädter

    2015-03-01

    Full Text Available While silica nanoparticles have enabled numerous industrial and medical applications, their toxicological safety requires further evaluation. Macrophages are the major cell population responsible for nanoparticle clearance in vivo. The prevailing macrophage phenotype largely depends on the local immune status of the host. Whereas M1-polarized macrophages are considered as pro-inflammatory macrophages involved in host defense, M2 macrophages exhibit anti-inflammatory and wound-healing properties, but also promote tumor growth.We employed different models of M1 and M2 polarization: GM-CSF/LPS/IFN-gamma was used to generate primary human M1 cells and M-CSF/IL-10 to differentiate M2 monocyte-derived macrophages. PMA-differentiated THP-1 cells were polarized towards an M1 type by LPS/IFN-gamma and towards M2 by IL-10. Uptake of fluorescent silica nanoparticles (Ø 26 and 41 nm and microparticles (Ø 1.75 µm was quantified. At the concentration used (50 µg/ml, silica nanoparticles did not influence cell viability as assessed by MTT assay. Nanoparticle uptake was enhanced in M2-polarized primary human monocyte-derived macrophages compared with M1 cells, as shown by flow cytometric and microscopic approaches. In contrast, the uptake of microparticles did not differ between M1 and M2 phenotypes. M2 polarization was also associated with increased nanoparticle uptake in the macrophage-like THP-1 cell line. In accordance, in vivo polarized M2-like primary human tumor-associated macrophages (TAM obtained from lung tumors took up more nanoparticles than M1-like alveolar macrophages isolated from the surrounding lung tissue.In summary, our data indicate that the M2 polarization of macrophages promotes nanoparticle internalization. Therefore, the phenotypical differences between macrophage subsets should be taken into consideration in future investigations on nanosafety, but might also open up therapeutic perspectives allowing to specifically target M2

  6. MEK1/2 Inhibition Promotes Macrophage Reparative Properties1

    Science.gov (United States)

    Long, Matthew E.; Eddy, William E.; Gong, Ke-Qin; Lovelace-Macon, Lara L.; McMahan, Ryan S.; Charron, Jean; Liles, W. Conrad; Manicone, Anne M.

    2016-01-01

    Macrophages have important functional roles in regulating the timely promotion and resolution of inflammation. While many of the intracellular signaling pathways involved in the pro-inflammatory responses of macrophages are well characterized, the components that regulate macrophage reparative properties are less well understood. We identified the MEK1/2 pathway as a key regulator of macrophage reparative properties. Pharmacological inhibition of the MEK1/2 pathway (MEKi) significantly increased expression of IL-4/IL-13 (M2) responsive genes in murine bone marrow-derived and alveolar macrophages. Deletion of the MEK1 gene using LysMCre+/+MEK1fl/fl macrophages as an alternate approach yielded similar results. MEKi enhanced STAT6 phosphorylation, and MEKi induced changes in M2 polarization were dependent on STAT6. In addition, MEKi-treatment significantly increased both murine and human macrophage efferocytosis of apoptotic cells (AC) independent of macrophage polarization and STAT6. These phenotypes were associated with increased gene and protein expression of Mertk, Tyro3, and Abca1, three proteins that promote macrophage efferocytosis. We also studied the effects of MEKi on in vivo macrophage efferocytosis and polarization. MEKi treated mice had increased efferocytosis of apoptotic PMNs instilled into the peritoneum. Furthermore, administration of MEKi after LPS-induced lung injury led to improved recovery of weight, fewer neutrophils in the alveolar compartment, and greater macrophage M2 polarization. Collectively, these results show that MEK1/2 inhibition is capable of promoting reparative properties of both murine and human macrophages. These studies suggest that the MEK1/2 pathway may be a therapeutic target to promote the resolution of inflammation via modulation of macrophage functions. PMID:28003382

  7. Burkholderia pseudomallei transcriptional adaptation in macrophages

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    Chieng Sylvia

    2012-07-01

    Full Text Available Abstract Background Burkholderia pseudomallei is a facultative intracellular pathogen of phagocytic and non-phagocytic cells. How the bacterium interacts with host macrophage cells is still not well understood and is critical to appreciate the strategies used by this bacterium to survive and how intracellular survival leads to disease manifestation. Results Here we report the expression profile of intracellular B. pseudomallei following infection of human macrophage-like U937 cells. During intracellular growth over the 6 h infection period, approximately 22 % of the B. pseudomallei genome showed significant transcriptional adaptation. B. pseudomallei adapted rapidly to the intracellular environment by down-regulating numerous genes involved in metabolism, cell envelope, motility, replication, amino acid and ion transport system and regulatory function pathways. Reduced expression in catabolic and housekeeping genes suggested lower energy requirement and growth arrest during macrophage infection, while expression of genes encoding anaerobic metabolism functions were up regulated. However, whilst the type VI secretion system was up regulated, expression of many known virulence factors was not significantly modulated over the 6hours of infection. Conclusions The transcriptome profile described here provides the first comprehensive view of how B. pseudomallei survives within host cells and will help identify potential virulence factors and proteins that are important for the survival and growth of B. pseudomallei within human cells.

  8. Macrophages as drivers of an opportunistic infection

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    Annette C. Vergunst

    2017-09-01

    Full Text Available Opportunistic pathogens are a worldwide cause of mortality and morbidity, and infections with intrinsically antibiotic-resistant pathogens have a large clinical, social and economic impact. Bacteria belonging to the Burkholderia cepacia complex (Bcc, ubiquitous in natural and industrial environments, are notorious pathogens for individuals with cystic fibrosis (CF. In addition, Burkholderia cenocepacia is emerging as the culprit of non-CF related, sometimes fatal infections. Knowledge of the underlying infection mechanism of these pathogens is important for efficient treatment, however, to date not much is known about the lifestyle of Bcc bacteria during infection. In our recent study published in PLoS Pathogens, we provide experimental evidence that macrophages are critically important for proliferation of B. cenocepacia, and are major drivers of fatal pro-inflammatory infections in zebrafish larvae. This is in agreement with recent clinical information showing that B. cenocepacia is mainly localised in phagocytes in infected CF lungs. A predominant intramacrophage stage and a host-detrimental role for macrophages have major implications for treatment strategies of both CF and non-CF infections. Intracellular survival of bacteria traditionally classified as extracellular, including Staphylococcus aureus and Pseudomonas aeruginosa, is an emerging theme. Our finding that macrophages are essential for proliferation of B. cenocepacia in the host suggests a new paradigm for Bcc infections and urges the development of novel anti-infectious therapies to efficiently disarm these intrinsically antibiotic resistant facultative intracellular pathogens.

  9. Pegylated silica nanoparticles: cytotoxicity and macrophage uptake

    Science.gov (United States)

    Glorani, Giulia; Marin, Riccardo; Canton, Patrizia; Pinto, Marcella; Conti, Giamaica; Fracasso, Giulio; Riello, Pietro

    2017-08-01

    Here, we present a thorough study of pegylated silica nanoparticle (SNP) interaction with different biological environments. The SNPs have a mean diameter of about 40 nm and are coated with polyethylene glycol (PEG) of different molecular weights. The physicochemical characterization of SNPs allowed the confirmation of the binding of PEG chains to the silica surface, the reproducibility of the synthesis and the narrow size-dispersion. In view of clarifying the SNP interaction with biological environments, we first assessed the SNP reactivity after the incubation with two cell lines (macrophages RAW 264.7 and primary human fibroblasts), observing a reduced toxicity of pegylated SNPs compared to the bare ones. Then, we investigated the effect of the protein adsorption on the SNP surface using the model serum protein, bovine serum albumin (BSA). We found that the protein adsorption takes place more heavily on poorly pegylated SNPs, promoting the uptake of the latter by macrophages and leading to an increased mortality of these cells. To better understand this mechanism by means of flow cytometry, the dye Ru(bpy)3Cl2 was incorporated in the SNPs. The overall results highlight the SNP potentialities as a drug delivery system, thanks to the low interactions with the macrophages.

  10. Regenerative Capacity of Macrophages for Remyelination

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    Khalil eRawji

    2016-05-01

    Full Text Available White matter injury, consisting of loss of axons, myelin and oligodendrocytes, is common in many neurological disorders and is believed to underlie several motor and sensory deficits. Remyelination is the process in which the insulative myelin sheath is restored to axons, thereby facilitating recovery from functional loss. Remyelination proceeds with oligodendrocyte precursor cells that differentiate into oligodendrocytes to synthesize the new myelin sheath after demyelination. This process is influenced by several factors, including trophic factors, inhibitory molecules in the lesion microenvironment, age of the subject, as well as the inflammatory response. Currently studied strategies that enhance remyelination consist of pharmacological approaches that directly induce oligodendrocyte precursor cell differentiation or using agents to neutralize the inhibitory microenvironment. Another strategy is to harness a reparative inflammatory response. This response, coordinated by central nervous system resident microglia and peripherally-derived infiltrating macrophages, has been shown to be important in the remyelination process. These innate immune cells perform important functions in remyelination, including the proteolysis and phagocytosis of inhibitory molecules present in the lesion microenvironment, the provision of trophic and metabolic factors to oligodendrocyte precursor cells, in addition to iron handling capacity. Additionally, an initial pro-inflammatory phase followed by a regulatory/anti-inflammatory phase has been shown to be important for oligodendrocyte precursor cell proliferation and differentiation, respectively. This review will discuss the beneficial roles of macrophages/microglia in remyelination and discuss therapeutic strategies to obtain the optimal regenerative macrophage phenotype for enhanced remyelination.

  11. Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mice.

    Science.gov (United States)

    Bijnen, Mitchell; Josefs, Tatjana; Cuijpers, Ilona; Maalsen, Constantijn J; van de Gaar, José; Vroomen, Maria; Wijnands, Erwin; Rensen, Sander S; Greve, Jan Willem M; Hofker, Marten H; Biessen, Erik A L; Stehouwer, Coen D A; Schalkwijk, Casper G; Wouters, Kristiaan

    2017-10-26

    Obesity is a risk factor for non-alcoholic steatohepatitis (NASH). This risk has been attributed to visceral adipose tissue (vAT) expansion associated with increased proinflammatory mediators. Accumulation of CD11c + proinflammatory adipose tissue macrophages (ATM) is an important driver of vAT inflammation. We investigated the role of ATMs in hepatic inflammation during NASH development. vAT isolated from lean, obese or ATM-depleted (using clodronate liposomes) obese mice was transplanted to lean ldlr -/- acceptor mice. Systemic and hepatic inflammation was assessed either after 2 weeks on standard chow or after 8 weeks on high cholesterol diet (HCD) to induce NASH. Transplanting donor vAT from obese mice increased HCD-induced hepatic macrophage content compared with lean-transplanted mice, worsening liver damage. ATM depletion prior to vAT transplantation reduced this increased hepatic macrophage accumulation. On chow, vAT transplantation induced a more pronounced increase in circulating and hepatic neutrophil numbers in obese-transplanted than lean-transplanted mice, while ATM depletion prior to vAT transplantation reversed this effect. Microarray analysis of fluorescence-activated cell sorting of CD11c + and CD11c - macrophages isolated from donor adipose tissue showed that obesity resulted in enhanced expression of neutrophil chemotaxis genes specifically in CD11c + ATMs. Involvement of the neutrophil chemotaxis proteins, CXCL14 and CXCL16, was confirmed by culturing vAT. In humans, CD11c expression in vAT of obese individuals correlated with vAT expression of neutrophil chemotactic genes and with hepatic expression of neutrophil and macrophage marker genes. ATMs from obese vAT induce hepatic macrophage accumulation during NASH development, possibly by enhancing neutrophil recruitment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise

  12. Mycobacterium bovis Bacillus Calmette–Guérin Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function

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    Ricardo D. Lardone

    2017-08-01

    Full Text Available Intralesional Mycobacterium bovis bacillus Calmette–Guérin (BCG has long been a relatively inexpensive therapy for inoperable cutaneous metastatic melanoma (CMM, although intralesional BCG skin mechanisms remain understudied. We analyzed intralesional BCG-treated CMM lesions combined with in vitro studies to further investigate BCG-altered pathways. Since macrophages play a pivotal role against both cancer and mycobacterial infections, we hypothesized BCG regulates macrophages to promote antitumor immunity. Tumor-associated macrophages (M2 infiltrate melanomas and impair antitumor immunity. BCG-treated, in vitro-polarized M2 (M2-BCG showed transcriptional changes involving inflammation, immune cell recruitment, cross talk, and activation pathways. Mechanistic network analysis indicated M2-BCG potential to improve interferon gamma (IFN-γ responses. Accordingly, frequency of IFN-γ-producing CD4+ T cells responding to M2-BCG vs. mock-treated M2 increased (p < 0.05. Moreover, conditioned media from M2-BCG vs. M2 elevated the frequency of granzyme B-producing CD8+ tumor-infiltrating lymphocytes (TILs facing autologous melanoma cell lines (p < 0.01. Furthermore, transcriptome analysis of intralesional BCG-injected CMM relative to uninjected lesions showed immune function prevalence, with the most enriched pathways representing T cell activation mechanisms. In vitro-infected MM-derived cell lines stimulated higher frequency of IFN-γ-producing TIL from the same melanoma (p < 0.05. Our data suggest BCG favors antitumor responses in CMM through direct/indirect effects on tumor microenvironment cell types including macrophages, T cells, and tumor itself.

  13. [Macrophages in central nervous canine distemper: friends or foes?].

    Science.gov (United States)

    Griot, C; Bürge, T; Brigger, S; Richard, A; Peterhans, E; Vandevelde, M

    1989-01-01

    Brain macrophages play an important role in the CNS. We review some biological aspects of brain macrophages in vivo and in vitro. The criteria and methods used for the identification of these cells are considered. They include some morphological features such as the use of histochemical and immunocytochemical techniques for internal and surface components. In the second part of this review, we describe the role of brain macrophages in canine distemper encephalitis as proposed earlier by us. Studies in cultured dog glial cells infected with canine distemper virus (CDV) have shown that brain macrophages stimulated by anti-CDV antibodies will release reactive oxygen species as measured by chemiluminescence. This response depends on the presence of viral antigens on the surfaces of infected cells and is mediated by the interaction of antigen-bound antibodies with Fc receptors on brain macrophages. These observations support the hypotheses that brain macrophages may contribute to the damage of the white matter observed in canine distemper encephalitis.

  14. Origins and Hallmarks of Macrophages: Development, Homeostasis, and Disease

    Science.gov (United States)

    Wynn, Thomas A.; Chawla, Ajay; Pollard, Jeffrey W.

    2013-01-01

    Preface Macrophages the most plastic cells of the hematopoietic system are found in all tissues and exhibit great functional diversity. They have roles in development, homeostasis, tissue repair, and immunity. While anatomically distinct, resident tissue macrophages exhibit different transcriptional profiles, and functional capabilities, they are all required for the maintenance of homeostasis. However, these reparative and homeostatic functions can be subverted by chronic insults, resulting in a causal association of macrophages with disease states. In this review, we discuss how macrophages regulate normal physiology and development and provide several examples of their pathophysiologic roles in disease. We define the “hallmarks” of macrophages performing particular functions, taking into account novel insights into the diversity of their lineages, identity, and regulation. This diversity is essential to understand because macrophages have emerged as important therapeutic targets in many important human diseases. PMID:23619691

  15. Tumor-Associated Macrophages in Oncolytic Virotherapy: Friend or Foe?

    Directory of Open Access Journals (Sweden)

    Nicholas L. Denton

    2016-07-01

    Full Text Available Cancer therapy remains a challenge due to toxicity limitations of chemotherapy and radiation therapy. Oncolytic viruses that selectively replicate and destroy cancer cells are of increasing interest. In addition to direct cell lysis, these vectors stimulate an anti-tumor immune response. A key regulator of tumor immunity is the tumor-associated macrophage population. Macrophages can either support oncolytic virus therapy through pro-inflammatory stimulation of the anti-tumor response at the cost of hindering direct oncolysis or through immunosuppressive protection of virus replication at the cost of hindering the anti-tumor immune response. Despite similarities in macrophage interaction between adult and pediatric tumors and the abundance of research supporting macrophage modulation in adult tumors, there are few studies investigating macrophage modulation in pediatric cancers or modulation of immunotherapy. We review the current state of knowledge regarding macrophages in cancers and their influence on oncolytic virotherapy.

  16. Macrophages in cardiac homeostasis, injury responses and progenitor cell mobilisation

    Directory of Open Access Journals (Sweden)

    Alexander R. Pinto

    2014-11-01

    Full Text Available Macrophages are an immune cell type found in every organ of the body. Classically, macrophages are recognised as housekeeping cells involved in the detection of foreign antigens and danger signatures, and the clearance of tissue debris. However, macrophages are increasingly recognised as a highly versatile cell type with a diverse range of functions that are important for tissue homeostasis and injury responses. Recent research findings suggest that macrophages contribute to tissue regeneration and may play a role in the activation and mobilisation of stem cells. This review describes recent advances in our understanding of the role played by macrophages in cardiac tissue maintenance and repair following injury. We examine the involvement of exogenous and resident tissue macrophages in cardiac inflammatory responses and their potential activity in regulating cardiac regeneration.

  17. Macrophage Function in Early Dissemination and Dormancy of Breast Cancer

    Science.gov (United States)

    2015-09-01

    AWARD NUMBER: W81XWH-14-1-0365 TITLE: Macrophage Functions in Early Dissemination and Dormancy of Breast Cancer PRINCIPAL INVESTIGATOR: Nina...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Macrophage Function in Early Dissemination and Dormancy of Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0365...13. SUPPLEMENTARY NOTES 14. ABSTRACT This research project focuses on the role of macrophages in early dissemination and dormancy . We hypothesized

  18. Ameloginins promote an alternatively activated macrophage phenotype in vitro

    DEFF Research Database (Denmark)

    Almqvist, S; Werthen, M; Lyngstadas, SP

    2011-01-01

    Amelogenins are extracellular matrix proteins used for the topical treatment of chronically inflamed tissues. The influence of amelogenins on human monocyte-derived macrophages was studied by measuring the concentrations of cytokines in culture supernatants. The interactions of cells and protein...... increased the macrophage release of key cell mediators involved in tissue repair. The effect was independent of phagocytosis, implying a receptor-mediated signal. The markedly increased levels of AMAC-1 suggest that amelogenins promote a reparative macrophage phenotype....

  19. Macrophage Responses to Epithelial Dysfunction Promote Lung Fibrosis in Aging

    Science.gov (United States)

    2017-10-01

    monocyte-derived alveolar macrophages based on single cell molecular classification in patients with pulmonary fibrosis. We have recruited a planned number...of patients into the study and performed transcriptional profiling by means of RNA-seq on single cell and bulk sorted populations or alveolar...macrophages. Major findings: In agreement with our hypothesis, using single cell RNA-seq, we found substantial heterogeneity of alveolar macrophages in the

  20. Ameloginins promote an alternatively activated macrophage phenotype in vitro

    DEFF Research Database (Denmark)

    Almqvist, S; Werthen, M; Lyngstadas, SP

    2011-01-01

    aggregates were visualised by transmission electron microscopy. The amelogenin treatment of macrophages increased several pro- and anti-inflammatory cytokines, including alternative macrophage activation marker AMAC-1 (p ...Amelogenins are extracellular matrix proteins used for the topical treatment of chronically inflamed tissues. The influence of amelogenins on human monocyte-derived macrophages was studied by measuring the concentrations of cytokines in culture supernatants. The interactions of cells and protein...... independent of cytochalasin B, although amelogenin aggregates were ingested by macrophages. Amelogenin effect was compared with that of tyrosine-rich amelogenin peptide, which apart from augmented VEGF levels (p

  1. Macrophages: An Inflammatory Link between Angiogenesis and Lymphangiogenesis

    Science.gov (United States)

    Corliss, Bruce A.; Azimi, Mohammad S.; Munson, Jenny; Peirce, Shayn M.; Murfee, Walter Lee

    2015-01-01

    Angiogenesis and lymphangiogenesis often occur in response to tissue injury or in the presence of pathology (e.g. cancer), and it is these types of environments in which macrophages are activated and increased in number. Moreover, the blood vascular microcirculation and the lymphatic circulation serve as the conduits for entry and exit for monocyte-derived macrophages in nearly every tissue and organ. Macrophages both affect and are affected by the vessels through which they travel. Therefore, it is not surprising that examination of macrophage behaviors in both angiogenesis and lymphangiogenesis has yielded interesting observations that suggest macrophages may be key regulators of these complex growth and remodeling processes. In this review, we will take a closer look at macrophages through the lens of angiogenesis and lymphangiogenesis, examining how their dynamic behaviors may regulate vessel sprouting and function. We present macrophages as a cellular link that spatially and temporally connects angiogenesis with lymphangiogenesis, in both physiological growth and in pathological adaptations, such as tumorigenesis. As such, attempts to therapeutically target macrophages in order to affect these processes may be particularly effective, and studying macrophages in both settings will accelerate the field’s understanding of this important cell type in health and disease. PMID:26614117

  2. Functional modifications of macrophage activity after sublethal irradiation

    International Nuclear Information System (INIS)

    Swartz, R.P.

    1982-01-01

    The modifications of macrophage activity following sublethal irradiation, both in vivo and in vitro, were studied using spreading and C3b-receptor-mediated ingestion assays. Nonelicited peritoneal washout cells were examined for changes in activity and selected population characteristics. The cells from irradiated mice were from a resident peritoneal population and not immigrating cells. The macrophage population showed enhanced activity early with a refractory period (24-48) when the macrophages were unresponsive to stimulation by irradiated lymphocytes. The enhanced activity was inversely dose dependent on macrophage. The lymphocytes showed a regulatory function(s) on the time post irradiation at which they were examined. Early lymphocytes exhibited the ability to enhance the activity of normal macrophages while lymphocytes removed 24 hours post irradiation could suppress the activity of already activated macrophages. The effect(s) of the various lymphocyte populations were reproduced with cell-free supernatants which was indicative of the production of lymphokines. Separation on nylon wool columns indicated that the activity resided primarily in the T-cell population of lymphocytes. In vitro irradiation indicated that stimulation of the lymphocytes is macrophage dependent. Additional work indicated that sublethally irradiated macrophages did not inhibit replication of the coccidian protozoon Toxoplasma gondii although they did show increased phagocytosis. Examination of the serum from whole body irradiated mice showed the presence of a postirradiation substance which enhanced the phagocytosis of normal macrophages. It was not present in the serum of normal mice and was not endotoxin

  3. Macrophage migration inhibitory factor is associated with aneurysmal expansion

    DEFF Research Database (Denmark)

    Pan, Jie-Hong; Lindholt, Jes Sanddal; Sukhova, Galina K

    2003-01-01

    Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution o...... of MIF to these human diseases remain unknown, although a recent rabbit study showed expression of this cytokine in atherosclerotic lesions.......Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine released mainly from macrophages and activated lymphocytes. Both atherosclerosis and abdominal aortic aneurysm (AAA) are inflammatory diseases tightly linked to the function of these cells. The correlation and contribution...

  4. Autologous bone marrow transplantation following chemotherapy and irradiation in dogs with spontaneous lymphomas

    International Nuclear Information System (INIS)

    Bowles, C.A.; Bull, M.; McCormick, K.; Kadin, M.; Lucas, D.

    1980-01-01

    Thirty dogs with spontaneous lymphomas were administered two to six cycles of chemotherapy and were randomized into 3 groups to receive 800 rads of total body irradiation and autologous bone marrow transplantation. Of 10 dogs irradiated after chemotherapy-induced remission and infused with remission marrow (group 1), 8 (80%) had successful grafts and experienced remissions lasting 62 to 1024 days. Of 9 dogs irradiated during remission and infused with remission marrow mixed with autologous tumor cells (group 2), 6 (66%) had remission lasting 15 to 45 days. Eleven dogs with progressive tumor growth (relapse) following chemotherapy were irradiated and infused with remission marrow (group 3). Tumor remission lasting 39 to 350 days was observed in 5 dogs (45%) in this group, and 6 dogs died in less than 30 days. Dogs in groups 1 to 3 had median survival times of 216, 60, and 45 days, respectively. The prolonged survival times for dogs in group 1 compared to dogs in groups 2 and 3 suggest that protocols involving irradiation and autologous marrow grafting in this model would be most effective when these protocols are applied to animals having a minimum tumor burden at the time of irradiation and when the grafting is done with tumor-free autologous marrow

  5. beta-TCP Versus Autologous Bone for Repair of Alveolar Clefts in a Goat Model.

    NARCIS (Netherlands)

    Ruiter, A. de; Meijer, G.J.; Dormaar, T.; Janssen, N.; Bilt, A. van der; Slootweg, P.J.; Bruijn, J. de; Rijn, L. van; Koole, R.A.

    2011-01-01

    Objective : The aim of this study in goats was to test the hypothesis that a novel synthetic bone substitute beta tricalcium phosphate (beta-TCP) can work as well as autologous bone harvested from the iliac crest for grafting and repair of alveolar clefts. Design : Ten adult Dutch milk goats ( Capra

  6. Experimental results and clinical impact of using autologous rectus fascia sheath for vascular replacement

    NARCIS (Netherlands)

    Kobori, Laszlo; Nemeth, Tibor; Nagy, Peter; Dallos, Gabor; Sotonyi, Peter; Fehervari, Imre; Nemes, Balazs; Gorog, Denes; Patonai, Attila; Monostory, Katalin; Doros, Attila; Sarvary, Enikoe; Fazakas, Janos; Gerlei, Zsuzsanna; Benkoe, Tamas; Piros, Laszlo; Jaray, Jeno; De Jong, Koert P.

    Vascular complications are major causes of graft failure in liver transplantation. The use of different vascular grafts is common but the results are controversial. The aim of this study was to create an 'ideal' arterial interponate for vascular replacements in the clinical field. An autologous,

  7. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury

    Science.gov (United States)

    Masuzawa, Akihiro; Black, Kendra M.; Pacak, Christina A.; Ericsson, Maria; Barnett, Reanne J.; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B.; Levitsky, Sidney; Cowan, Douglas B.

    2013-01-01

    Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 106/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2–8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

  8. [Construction of a capsular tissue-engineered ureteral stent seeded with autologous urothelial cells].

    Science.gov (United States)

    Tan, Haisong; Fu, Weijun; Li, Jianqiang; Wang, Zhongxin; Li, Gang; Ma, Xin; Dong, Jun; Gao, Jiangping; Wang, Xiaoxiong; Zhang, Xu

    2013-01-01

    To investigate the feasibility of constructing a capsular poly L-lactic acid (PLLA) ureteral stent seeded with autologous urothelial cells using tissue engineering methods. The capsular ureteral stent was constructed by subcutaneously embedding PLLA ureteral stent in the back of beagles for 3 weeks to induce the formation of connective tissue on the surfaces. After decellularization of the stent, the expanded autologous urothelial cells were seeded on the stent. The surface structure and cell adhesion of the stent were observed using HE staining, scanning electron microscope (SEM) and immunocytochemical staining. MTT assay was used to evaluate urothelial cell proliferation on the capsular PLLA ureteral stent and on circumferential small intestinal submucosa graft. HE staining and VIII factor immunohistochemistry revealed numerous capillaries in the connective tissue encapsulating the stent without obvious local inflammatory response. The results of SEM and immunocytochemical staining showed that the capsule contained rich collagenic fibers forming three-dimensional structures, and the seeded autologous urothelial cells could adhere and well aligned on the surface. MTT assay showed normal growth of the cells on the stent as compared with the cells grown on circumferential small intestinal submucosa graft. The capsular PLLA ureteral stent allows adhesion and proliferation of autologous urothelial cells and shows a potential in applications of constructing tissue-engineered ureter.

  9. Specific Factors Influence the Success of Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Thissiane L. Gonçalves

    2009-01-01

    Full Text Available Successful hematopoietic stem cell transplantation (HSCT, both autologous and allogeneic, requires a rapid and durable engraftment, with neutrophil (>500/µL and platelet (>20,000/µL reconstitution. Factors influencing engraftment after autologous or allogeneic HSCT were investigated in 65 patients: 25 autologous peripheral stem cell transplantation (PBSCT and 40 allogeneic bone marrow transplantation (BMT patients. The major factor affecting engraftment was the graft source for HSCT. Neutrophil and platelet recovery were more rapid in autologous PBSCT than in allogeneic BMT [neutrophil occurring in median on day 10.00 (09.00/11.00 and 19.00 (16.00/23.00 and platelet on day 11.00 (10.00/13.00 and 21.00 (18.00/25.00, respectively; p < 0.0001]. The type of disease also affected engraftment, where multiple myeloma (MM and lymphoma showed faster engraftment when compared with leukemia, syndrome myelodysplastic (SMD and aplastic anemia (AA and MM presented the best overall survival (OS in a period of 12 months. Other factors included the drug used in the conditioning regimen (CR, where CBV, melphalan (M-200 and FluCy showed faster engraftment and M-200 presented the best OS, in a period of 12 months and age, where 50–59 years demonstrated faster engraftment. Sex did not influence neutrophil and platelet recovery.

  10. Evidences of autologous fat grafting for the treatment of keloids and hypertrophic scars

    Directory of Open Access Journals (Sweden)

    VINÍCIUS ZOLEZI DA SILVA

    Full Text Available SUMMARY Introduction Since the 1980s, the use of autologous fat grafting has been growing in plastic surgery. Recently, this procedure has come to be used as a treatment for keloids and hypertrophic scars mainly due to the lack of satisfactory results with other techniques. So far, however, it lacks more consistent scientific evidence to recommend its use. The aim of this study was to review the current state of autologous fat grafting for the treatment of keloids and hypertrophic scars, their benefits and scientific evidences in the literature. Method A review in the Pubmed database was performed using the keywords “fat grafting and scar”, “fat grafting and keloid scar” and “fat grafting and hypertrophic scar.” Inclusion criteria were articles written in English and published in the last 10 years, resulting in 15 studies. Results These articles indicate that autologous fat grafting carried out at sites with pathological scars leads to a reduction of the fibrosis and pain, an increased range of movement in areas of scar contraction, an increase in their flexibility, resulting in a better quality of scars. Conclusion So far, evidences suggest that autologous fat grafting for the treatment of keloids and hypertrophic scars is associated with a better quality of scars, leading to esthetic and functional benefits. However, this review has limitations and these findings should be treated with reservations, since they mostly came from studies with low levels of evidence.

  11. No positive effect of autologous platelet gel after total knee arthroplasty

    NARCIS (Netherlands)

    Peerbooms, Joost C.; de Wolf, Gideon S.; Colaris, Joost W.; Bruijn, Daniël J.; Verhaar, Jan A. N.

    2009-01-01

    Activated platelets release a cocktail of growth factors, some of which are thought to stimulate repair. We investigated whether the use of autologous platelet gel (PG) in total knee arthroplasty (TKA) would improve wound healing and knee function, and reduce blood loss and the use of analgesics.

  12. Autologous stem cell transplantation in treatment of aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Kluin-Nelemans, Hanneke

    2002-01-01

    There is no doubt that autologous stem cell transplantation is useful for patients with relapsed aggressive non-Hodgkin's lymphoma if they are responsive to the chemotherapy given before the transplantation. A small subset of patients with primary refractory disease still profits from this high dose

  13. Comparison of upfront tandem autologous-allogeneic transplantation versus reduced intensity allogeneic transplantation for multiple myeloma

    NARCIS (Netherlands)

    Sahebi, F.; Iacobelli, S.; Biezen, A.V.; Volin, L.; Dreger, P.; Michallet, M.; Ljungman, P.T.; Witte, T.J. de; Henseler, A.; Schaap, N.P.M.; Lopez-Corral, L.; Poire, X.; Passweg, J.; Hamljadi, R.M.; Thomas, S.H.; Schonland, S.; Gahrton, G.; Morris, C.; Kroger, N.; Garderet, L.

    2015-01-01

    We performed a retrospective analysis of the European Group for Blood and Marrow Transplantation database comparing the outcomes of multiple myeloma patients who received tandem autologous followed by allogeneic PSCT (auto-allo) with the outcomes of patients who underwent a reduced intensity

  14. Hemolytic uremic syndrome after high dose chemotherapy with autologous stem cell support

    NARCIS (Netherlands)

    van der Lelie, H.; Baars, J. W.; Rodenhuis, S.; Van Dijk, M. A.; de Glas-Vos, C. W.; Thomas, B. L.; van Oers, R. H.; von dem Borne, A. E.

    1995-01-01

    BACKGROUND: Chemotherapy intensification may lead to new forms of toxicity such as hemolytic uremic syndrome. METHODS: Three patients are described who developed this complication 4 to 6 months after high dose chemotherapy followed by autologous stem cell support. The literature on this subject is

  15. Severe encephalopathy after high-dose chemotherapy with autologous stem cell support for brain tumours

    NARCIS (Netherlands)

    van den Berkmortel, F.; Gidding, C.; de Kanter, M.; Punt, C. J. A.

    2006-01-01

    Recurrent medulloblastoma carries a poor prognosis. Long-term survival has been obtained with high-dose chemotherapy with autologous stem cell transplantation and secondary irradiation. A 21-year-old woman with recurrent medulloblastoma after previous chemotherapy and radiotherapy is presented. The

  16. Socket grafting with the use of autologous bone: an experimental study in the dog.

    Science.gov (United States)

    Araújo, Mauricio G; Lindhe, Jan

    2011-01-01

    studies in humans and animals have shown that following tooth removal (loss), the alveolar ridge becomes markedly reduced. Attempts made to counteract such ridge diminution by installing implants in the fresh extraction sockets were not successful, while socket grafting with anorganic bovine bone mineral prevented ridge contraction. to examine whether grafting of the alveolar socket with the use of chips of autologous bone may allow ridge preservation following tooth extraction. in five beagle dogs, the distal roots of the third and fourth mandibular premolars were removed. The sockets in the right or the left jaw quadrant were grafted with either anorganic bovine bone or with chips of autologous bone harvested from the buccal bone plate. After 3 months of healing, biopsies of the experimental sites were sampled, prepared for buccal-lingual ground sections and examined with respect to size and composition. it was observed that the majority of the autologous bone chips during healing had been resorbed and that the graft apparently did not interfere with socket healing or processes that resulted in ridge resorption. autologous bone chips placed in the fresh extraction socket will (i) neither stimulate nor retard new bone formation and (ii) not prevent ridge resorption that occurs during healing following tooth extraction.

  17. Effects of Autologous Fat and ASCs on Swine Hypertrophic Burn Scars: A Multimodal Quantitative Analysis

    Directory of Open Access Journals (Sweden)

    Scott J. Rapp, MD

    2017-11-01

    Conclusion:. Early results suggest that autologous fat and/or ASCs may improve healing of hypertrophic scarring by altering the cellular and structural components during wound remodeling up to 20 weeks after injury. This may have beneficial applications in early treatment of large or cosmetically sensitive immature burn scars.

  18. Autologous graft-versus-host disease induction in advanced breast cancer: role of peripheral bloodprogenitor cells

    NARCIS (Netherlands)

    Wall, E. van der; Horn, T.; Bright, E.; Passos-Coehlo, J-L.; Bond, S.; Clarke, B.; Altomonte, V.; McIntyre, K.; Vogelsang, G.; Noga, S.J.; Davis, J.M.; Thomassen, J.; Ohly, K.V.; Lee, S.M.; Fetting, J.; Armstrong, D.K.; Davidson, N.E.; Hess, A.D.; Kennedy, M.J.

    2000-01-01

    The purpose of the present study was to investigate the impact of the use of peripheral blood progenitor cells (PBPCs) on the induction of autologous graft-versus-host disease (GVHD) in patients with advanced breast cancer. 14 women with stage IIIB and 36 women with stage IV breast cancer received

  19. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma

    DEFF Research Database (Denmark)

    d'Amore, Francesco; Relander, Thomas; Lauritzsen, Grete F

    2012-01-01

    Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in PTCL, the Nordic Lymphoma Group (NLG) conducted a large...

  20. Treatment of Recurrent Corneal Epithelial Defect by Autologous Serum Eye Drop

    Directory of Open Access Journals (Sweden)

    Hossein Mohammad Rabei

    2015-02-01

    Full Text Available Background: The aim of the present study was to evaluate the efficacy of autologous serum eye drop in treatment of recurrent corneal epithelial defect.Materials and Methods: Fourteen patients with recurrent corneal epithelial defect were studied. Autologous serum was prepared from the patients and diluted in 20% normal saline. The patients were instructed to use the autologous serum every six hours. Patients were followed for a mean period of 18 months.Results: Four males (28.6% and 10 females (71.4% entered the study. Four patients stopped the treatment after three months with complete satisfaction from treatment. Patients reported a reduction in frequency and severity of attacks 4.6±2 weeks after the start of treatment. The mean number of attacks before the procedure was 7.6±0.9 per year which was reduced to 2.2±0.9 per year after treatment (p<0.001. The main side effects in patients were eye pruritus and redness which were well tolerated by patients.Conclusion: Autologous serum application seems to be a safe and effective method to treat recurrent corneal epithelial defect.

  1. Reaming debris as a novel source of autologous bone to enhance healing of bone defects

    NARCIS (Netherlands)

    Bakker, A.D.; Kroeze, R.J.; Korstjens, C.; Kleine, R.H.; Frolke, J.P.M.; Klein-Nulend, J.

    2011-01-01

    Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone

  2. Rituximab purging and/or maintenance in patients undergoing autologous transplantation for relapsed follicular lymphoma

    DEFF Research Database (Denmark)

    Pettengell, Ruth; Schmitz, Norbert; Gisselbrecht, Christian

    2013-01-01

    The objective of this randomized trial was to assess the efficacy and safety of rituximab as in vivo purging before transplantation and as maintenance treatment immediately after high-dose chemotherapy and autologous stem-cell transplantation (HDC-ASCT) in patients with relapsed follicular lymphoma...

  3. Repair of a large congenital frontal bone defect with autologous exchange cranioplasty.

    Science.gov (United States)

    Ropper, Alexander E; Rogers, Gary F; Ridgway, Emily B; Proctor, Mark R

    2010-11-01

    The authors report the case of a large idiopathic frontal bone defect and concomitant sagittal synostosis corrected by autologous exchange cranioplasty by using a corticocancellous bone graft and cranial vault expansion. An otherwise healthy, developmentally normal 6-year-old girl presented to our clinic with a large frontal bone defect. The osseous defect was midline and inferior to the coronal sutures, and the underlying dura was slightly tense. She had no signs or symptoms of increased intracranial pressure, and her head circumference and cephalic index were normal. Imaging demonstrated fusion of the sagittal synostosis. The defect was repaired using full-thickness autologous bone harvested from the bilateral parietal regions, which were widened using barrel-stave osteotomies to reduce pressure on the graft site in the setting of sagittal synostosis and mild cranial narrowing. The donor sites were covered with autologous particulate bone graft harvested from the endocortical surface of the grafted segments and the ectocortical surface of the intact parietal bones. The donor and recipient sites healed. Imaging revealed that the particulate bone healed with a thickness similar to the surrounding bone. This bony defect is analogous to parietal foramina and may have a similar etiopathogenesis. The technique of autologous exchange cranioplasty using corticocancellous particulate bone graft provides a simple and reliable method to repair large structural calvarial defects.

  4. Reaming debris as a novel source of autologous bone to enhance healing of bone defects

    NARCIS (Netherlands)

    Bakker, Astrid D.; Kroeze, Robert Jan; Korstjens, Clara; de Kleine, Ruben H.; Frolke, Jan Paul M.; Klein-Nulend, Jenneke

    Reaming debris is formed when bone defects are stabilized with an intramedullary nail, and contains viable osteoblast-like cells and growth factors, and might thus act as a natural osteoinductive scaffold. The advantage of using reaming debris over stem cells or autologous bone for healing bone

  5. Intrathecal application of autologous bone marrow cell preparations in parkinsonian syndromes

    DEFF Research Database (Denmark)

    Storch, Alexander; Csoti, Ilona; Eggert, Karla

    2012-01-01

    A growing number of patients is treated with intrathecal application of autologous bone marrow cells (aBMCs), but clinical data are completely lacking in movement disorders. We provide first clinical data on efficacy and safety of this highly experimental treatment approach in parkinsonian...

  6. Treatment of midshaft clavicular nonunion with plate fixation and autologous bone grafting

    DEFF Research Database (Denmark)

    Olsen, Bo Sanderhoff; Vaesel, M T; Søjbjerg, Jens Ole

    1995-01-01

    , and one had a failure. Thirteen of 16 patients were satisfied with the cosmetic outcome, assessing their cosmetic result as either good or excellent. Rigid plate fixation and restoration of clavicular length with autologous cancellous bone graft is recommended for the treatment of symptomatic clavicular...

  7. Multiple congenitally missing teeth: treatment outcome with autologous transplantation and orthodontic space closure.

    Science.gov (United States)

    Fiorentino, Giuseppe; Vecchione, Pietro

    2007-11-01

    Treatment for patients with congenitally missing teeth can be challenging. The treatment options include retaining the deciduous teeth, extracting the deciduous teeth and allowing the space to close spontaneously, implant replacement, autotransplantation, prosthetic replacement, and orthodontic space closure. Autologous transplantation and space closure with orthodontic appliances are demonstrated in this case report.

  8. Use of autologous grafts in the treatment of acquired penile curvature: An experience of 33 cases

    Directory of Open Access Journals (Sweden)

    Abdul Rouf Khawaja

    2016-01-01

    Conclusion: Tunical lengthening procedures by autologous free grafts represents a safe and reproducible technique. A good preoperative erectile function is required for tunical lengthening procedure. Temporalis fascia graft is thin, tough membrane and effective graft for PD with good cosmetic and functional results.

  9. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    Science.gov (United States)

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). Copyright © 2016. Published by Elsevier Inc.

  10. Investigation of an autologous blood treatment strategy for temporomandibular joint hypermobility in a pig model

    Czech Academy of Sciences Publication Activity Database

    Štembírek, Jan; Matalová, Eva; Buchtová, Marcela; Machoň, V.; Míšek, Ivan

    2013-01-01

    Roč. 42, č. 3 (2013), s. 369-375 ISSN 0901-5027 Grant - others:GA MŠk(CZ) 1M0528 Institutional support: RVO:67985904 Keywords : temporomandibular joint * pig * autologous blood * hypermobility Subject RIV: FF - HEENT, Dentistry Impact factor: 1.359, year: 2013

  11. Lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with lectins

    International Nuclear Information System (INIS)

    Mazumder, A.; Grimm, E.A.; Zhang, H.Z.; Rosenberg, S.A.

    1982-01-01

    Human peripheral blood lymphocytes (PBL), obtained from patients with a variety of cancers, were incubated in vitro with phytohemagglutinin, concanavalin A, and crude or lectin-free T-cell growth factors. The lectin-activated PBL of nine patients were capable of lysing fresh autologous tumor during a 4-hr 51Cr release assay. Multiple metastases from the same patient were equivalently lysed by these activated autologous PBL. No lysis of fresh PBL or lectin-induced lymphoblast cell targets was seen, although tumor, PBL, and lymphoblast cells were shown to be equally lysable using allosensitized cells. The activated cells could be expanded without loss of cytotoxicity in crude or lectin-free T-cell growth factors. The generation of cells lytic to fresh autologous tumor was dependent on the presence of adherent cells, although the lytic cell itself was not adherent. Proliferation was not involved in the induction of lytic cells since equal lysis was induced in irradiated and nonirradiated lymphocytes. Lectin was not required in the lytic assay, and the addition of alpha-methyl-D-mannoside to concanavalin A-activated lymphoid cells did not increase the lysis of fresh tumor cells. Activation by lectin for 3 days appears to be an efficient and convenient method for generating human cells lytic to fresh autologous tumor. These lytic cells may be of value for studies of the cell-mediated lysis of human tumor and possibly for tumor immunotherapy as well

  12. Harvest of autologous clavipectoral fascia for use in duraplasty: cadaveric feasibility study.

    Science.gov (United States)

    Louis, Robert G; Tubbs, R Shane; Mortazavi, Martin M; Shoja, Mohammadali M; Loukas, Marios; Cohen-Gadol, Aaron A

    2013-03-01

    Techniques and materials for repair of dural defects following neurosurgical procedures vary. Given higher complication rates with nonautologous duraplasty materials, most authors strongly recommend autologous grafts. To expand the arsenal of possible materials available to the neurosurgeon, we propose the use of autologous clavipectoral fascia as an alternative donor for duraplasty. Eight embalmed adult cadavers underwent dissection of the pectoral region. A 12-cm curvilinear skin incision was made 2 cm inferior to the nipple in males and along the inferior breast edge in females. Dissection was continued until the clavipectoral fascia was encountered, and a tissue plane was developed between this fascia and the deeper pectoralis major muscle. Sections of clavipectoral fascia were used for duraplasty in the same specimens. In all specimens, removal of clavipectoral fascia was easily performed with tissue separation between the overlying fascia and underlying muscle. Only small adhesions were found between the fascia and underlying muscle, and these were easily transected. No obvious gross neurovascular injuries were identified. Large portions of clavipectoral fascia were available, and at least a 10 × 10-cm piece (average thickness, 1.2 mm) was easily harvested for all specimens. Clavipectoral fascia shares characteristics with materials such as pericranium and fascia lata that have been used successfully in duraplasty, and most importantly, it is autologous. Theoretically, using clavipectoral fascia would reduce the risk of muscle herniation. It offers an alternative source for autologous dural grafting when other sources are unavailable or exhausted. Clinical experience with this fascia is warranted.

  13. Salmonella sepsis following posttraumatic splenectomy and implantation of autologous splenic tissue

    DEFF Research Database (Denmark)

    Schrøder, H M; Hovendal, C

    1985-01-01

    A severe complication following implantation of autologous splenic tissue occurred in a 51-year-old man. Indirect injury to abdomen resulted in a lesion of the splenic artery. Following splenectomy and reimplantation of splenic tissue into three pouches, a severe Salmonella sepsis developed within...

  14. Biodegradable p(DLLA-epsilon-CL) nerve guides versus autologous nerve grafts : Electromyographic and video analysis

    NARCIS (Netherlands)

    Meek, MF; Nicolai, JPA; Gramsbergen, A; van der Werf, J.F.A.

    The aim of this study was to evaluate the functional effects of bridging a gap in the sciatic nerve of the rat with either a biodegradable copolymer of (DL)-lactide and epsilon -caprolactone [p(DLLA-epsilon -CL)] nerve guide or an autologous nerve graft. Electromyograms (EMGs) of the gastrocnemius

  15. Poly(DL-lactide-epsilon-caprolactone) nerve guides perform better than autologous nerve grafts

    NARCIS (Netherlands)

    DenDunnen, WFA; VanderLei, B; Schakenraad, JM; Stokroos, [No Value; Blaauw, E; Pennings, AJ; Robinson, PH; Bartels, H.

    1996-01-01

    The aim of this study was to compare the speed and quality of nerve regeneration after reconstruction using a biodegradable nerve guide or an autologous nerve graft. We evaluated nerve regeneration using light microscopy, transmission electron microscopy and morphometric analysis. Nerve regeneration

  16. Physiological problems in patients undergoing autologous and allogeneic hematopoietic stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Sevgisun Kapucu

    2014-01-01

    Full Text Available Objective: Stem cell transplantation is usually performed in an effort to extend the patient′s life span and to improve their quality of life. This study was conducted to determine the postoperative physiological effects experienced by patients who had undergone autologous and allogeneic stem cell transplantation. Methods: The research is a descriptive study conducted with a sample of 60 patients at Stem Cell Transplantation Units in Ankara. Percentile calculation and chi-square tests were used to evaluate the data. Results: When a comparison was made between patients who had undergone allogeneic Hematopoietic stem cell transplantation (HSCT and those who had undergone autologous HSCT, results indicated that problems occurred more often for the allogeneic HSCT patients. The problems included: Digestion (94.3%, dermatological (76.7%, cardiac and respiratory (66.7%, neurological (66.7%, eye (56.7%, infections (26.7% and Graft Versus Host Disease (5 patients. Furthermore, the problems with pain (50%, numbness and tingling (40%, and speech disorders (3 patients were observed more often in autologous BMT patients. Conclusion: Autologous and allogeneic patients experienced most of physical problems due to they receive high doses of chemotherapy. Therefore, it is recommended that an interdisciplinary support team approach should be usedtohelp reduce and manage the problems that may arise during patient care.

  17. Substitutes of structural and non-structural autologous bone grafts in hindfoot arthrodeses and osteotomies: a systematic review.

    Science.gov (United States)

    Müller, Marc Andreas; Frank, Alexander; Briel, Matthias; Valderrabano, Victor; Vavken, Patrick; Entezari, Vahid; Mehrkens, Arne

    2013-02-07

    Structural and non-structural substitutes of autologous bone grafts are frequently used in hindfoot arthrodeses and osteotomies. However, their efficacy is unclear.The primary goal of this systematic review was to compare autologous bone grafts with structural and non-structural substitutes regarding the odds of union in hindfoot arthrodeses and osteotomies. The Medline and EMBASE and Cochrane databases were searched for relevant randomized and non-randomized prospective studies as well as retrospective comparative chart reviews. 10 studies which comprised 928 hindfoot arthrodeses and osteotomies met the inclusion criteria for this systematic review. The quality of the retrieved studies was low due to small samples sizes and confounding variables. The pooled random effect odds for union were 12.8 (95% CI 12.7 to 12.9) for structural allografts, 5.7 (95% CI 5.5 to 6.0) for cortical autologous grafts, 7.3 (95% CI 6.0 to 8.6) for cancellous allografts and 6.0 (95% CI 5.7 to 6.4) for cancellous autologous grafts. In individual studies, the odds of union in hindfoot arthrodeses achieved with cancellous autologous grafts was similar to those achieved with demineralised bone matrix or platelet derived growth factor augmented ceramic granules. Our results suggest an equivalent incorporation of structural allografts as compared to autologous grafts in hindfoot arthrodeses and osteotomies. There is a need for prospective randomized trials to further clarify the role of substitutes of autologous bone grafts in hindfoot surgery.

  18. Autologous whole blood versus corticosteroid local injection in treatment of plantar fasciitis: A randomized, controlled multicenter clinical trial.

    Science.gov (United States)

    Karimzadeh, Afshin; Raeissadat, Seyed Ahmad; Erfani Fam, Saleh; Sedighipour, Leyla; Babaei-Ghazani, Arash

    2017-03-01

    Plantar fasciitis is the most common cause of heel pain. Local injection modalities are among treatment options in patients with resistant pain. The aim of the present study was to evaluate the effect of local autologous whole blood compared with corticosteroid local injection in treatment of plantar fasciitis. In this randomized controlled multicenter study, 36 patients with chronic plantar fasciitis were recruited. Patients were allocated randomly into three treatment groups: local autologous blood, local corticosteroid injection, and control groups receiving no injection. Patients were assessed with visual analog scale (VAS), pressure pain threshold (PPT), and plantar fasciitis pain/disability scale (PFPS) before treatment, as well as 4 and 12 weeks post therapy. Variables of pain and function improved significantly in both corticosteroid and autologous blood groups compared to control group. At 4 weeks following treatment, patients in corticosteroid group had significantly lower levels of pain than patients in autologous blood and control groups (higher PPT level, lower PFPS, and VAS). After 12 weeks of treatment, both corticosteroid and autologous blood groups had lower average levels of pain than control group. The corticosteroid group showed an early sharp and then more gradual improvement in pain scores, but autologous blood group had a steady gradual drop in pain. Autologous whole blood and corticosteroid local injection can both be considered as effective methods in the treatment of chronic plantar fasciitis. These treatments decrease pain and significantly improve function compared to no treatment.

  19. Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction

    OpenAIRE

    Shabo, Ivan; Midtb?, Kristine; Andersson, Henrik; ?kerlund, Emma; Olsson, Hans; Wegman, Pia; Gunnarsson, Cecilia; Lindstr?m, Annelie

    2015-01-01

    Background: Cell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor st...

  20. Macrophage defense mechanisms against intracellular bacteria.

    Science.gov (United States)

    Weiss, Günter; Schaible, Ulrich E

    2015-03-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. © 2015 The Authors

  1. Macrophage defense mechanisms against intracellular bacteria

    Science.gov (United States)

    Weiss, Günter; Schaible, Ulrich E

    2015-01-01

    Macrophages and neutrophils play a decisive role in host responses to intracellular bacteria including the agent of tuberculosis (TB), Mycobacterium tuberculosis as they represent the forefront of innate immune defense against bacterial invaders. At the same time, these phagocytes are also primary targets of intracellular bacteria to be abused as host cells. Their efficacy to contain and eliminate intracellular M. tuberculosis decides whether a patient initially becomes infected or not. However, when the infection becomes chronic or even latent (as in the case of TB) despite development of specific immune activation, phagocytes have also important effector functions. Macrophages have evolved a myriad of defense strategies to combat infection with intracellular bacteria such as M. tuberculosis. These include induction of toxic anti-microbial effectors such as nitric oxide and reactive oxygen intermediates, the stimulation of microbe intoxication mechanisms via acidification or metal accumulation in the phagolysosome, the restriction of the microbe's access to essential nutrients such as iron, fatty acids, or amino acids, the production of anti-microbial peptides and cytokines, along with induction of autophagy and efferocytosis to eliminate the pathogen. On the other hand, M. tuberculosis, as a prime example of a well-adapted facultative intracellular bacterium, has learned during evolution to counter-balance the host's immune defense strategies to secure survival or multiplication within this otherwise hostile environment. This review provides an overview of innate immune defense of macrophages directed against intracellular bacteria with a focus on M. tuberculosis. Gaining more insights and knowledge into this complex network of host-pathogen interaction will identify novel target sites of intervention to successfully clear infection at a time of rapidly emerging multi-resistance of M. tuberculosis against conventional antibiotics. PMID:25703560

  2. Autologous fat transplantation: volumetric tools for estimation of volume survival. A systematic review.

    Science.gov (United States)

    Herold, Christian; Ueberreiter, Klaus; Busche, Marc N; Vogt, Peter M

    2013-04-01

    Autologous fat transplantation has gained great recognition in aesthetic and reconstructive surgery. Two main aspects are of predominant importance for progress control after autologous fat transplantation to the breast: quantitative information about the rate of fat survival in terms of effective volume persistence and qualitative information about the breast tissue to exclude potential complications of autologous fat transplantation. There are several tools available for use in evaluating the rate of volume survival. They are extensively compared in this review. The anthropometric method, thermoplastic casts, and Archimedes' principle of water displacement are not up to date anymore because of major drawbacks, first and foremost being reduced reproducibility and exactness. They have been replaced by more exact and reproducible tools such as MRI volumetry or 3D body surface scans. For qualitative and quantitative progress control, MRI volumetry offers all the necessary information: evaluation of fat survival and diagnostically valuable imaging to exclude possible complications of autologous fat transplantation. For frequent follow-up, e.g., monthly volume analysis, repeated MRI exams would not be good for the patient and are not cost effective. In these cases, 3D surface imaging is a good tool and especially helpful in a private practice setting where fast data acquisition is needed. This tool also offers the possibility of simulating the results of autologous fat transplantation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

  3. Gaucher cells demonstrate a distinct macrophage phenotype and resemble alternatively activated macrophages

    NARCIS (Netherlands)

    Boven, Leonie A.; van Meurs, Marjan; Boot, Rolf G.; Mehta, Atul; Boon, Louis; Aerts, Johannes M.; Laman, Jon D.

    2004-01-01

    Although the existence of anti-inflammatory alternatively activated macrophages (aamphi) has been accepted widely based on in vitro studies, their in. vivo location, phenotype, and function still are debated. Gaucher disease (GD) is caused by a genetic deficiency in the lysosomal enzyme

  4. DMPD: Signal integration between IFNgamma and TLR signalling pathways in macrophages. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16920490 Signal integration between IFNgamma and TLR signalling pathways in macroph...tml) (.csml) Show Signal integration between IFNgamma and TLR signalling pathways in macrophages. PubmedID 1...6920490 Title Signal integration between IFNgamma and TLR signalling pathways in

  5. Immunomodulatory Molecule IRAK-M Balances Macrophage Polarization and Determines Macrophage Responses during Renal Fibrosis.

    Science.gov (United States)

    Steiger, Stefanie; Kumar, Santhosh V; Honarpisheh, Mohsen; Lorenz, Georg; Günthner, Roman; Romoli, Simone; Gröbmayr, Regina; Susanti, Heni-Eka; Potempa, Jan; Koziel, Joanna; Lech, Maciej

    2017-08-15

    Activation of various innate immune receptors results in IL-1 receptor-associated kinase (IRAK)-1/IRAK-4-mediated signaling and secretion of proinflammatory cytokines such as IL-12, IL-6, or TNF-α, all of which are implicated in tissue injury and elevated during tissue remodeling processes. IRAK-M, also known as IRAK-3, is an inhibitor of proinflammatory cytokine and chemokine expression in intrarenal macrophages. Innate immune activation contributes to both acute kidney injury and tissue remodeling that is associated with chronic kidney disease (CKD). Our study assessed the contribution of macrophages in CKD and the role of IRAK-M in modulating disease progression. To evaluate the effect of IRAK-M in chronic renal injury in vivo, a mouse model of unilateral ureteral obstruction (UUO) was employed. The expression of IRAK-M increased within 2 d after UUO in obstructed compared with unobstructed kidneys. Mice deficient in IRAK-M were protected from fibrosis and displayed a diminished number of alternatively activated macrophages. Compared to wild-type mice, IRAK-M-deficient mice showed reduced tubular injury, leukocyte infiltration, and inflammation following renal injury as determined by light microscopy, immunohistochemistry, and intrarenal mRNA expression of proinflammatory and profibrotic mediators. Taken together, these results strongly support a role for IRAK-M in renal injury and identify IRAK-M as a possible modulator in driving an alternatively activated profibrotic macrophage phenotype in UUO-induced CKD. Copyright © 2017 by The American Association of Immunologists, Inc.

  6. Macrophage heterogeneity and cholesterol homeostasis: classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL.

    Science.gov (United States)

    Chu, Eugene M; Tai, Daven C; Beer, Jennifer L; Hill, John S

    2013-02-01

    Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumor necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ attenuated the ability of the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Iron Reduces M1 Macrophage Polarization in RAW264.7 Macrophages Associated with Inhibition of STAT1

    Directory of Open Access Journals (Sweden)

    Zhen-Shun Gan

    2017-01-01

    Full Text Available Iron metabolism in inflammation has been mostly characterized in macrophages exposed to pathogens or inflammatory conditions. The aim of this study is to investigate the cross-regulatory interactions between M1 macrophage polarization and iron metabolism. Firstly, we characterized the transcription of genes related to iron homeostasis in M1 RAW264.7 macrophages stimulated by IFN-γ. The molecular signature of M1 macrophages showed high levels of iron storage (ferritin, a low level of iron export (ferroportin, and changes of iron regulators (hepcidin and transferrin receptors, which favour iron sequestration in the reticuloendothelial system and are benefit for inflammatory disorders. Then, we evaluated the effect of iron on M1 macrophage polarization. Iron significantly reduced mRNA levels of IL-6, IL-1β, TNF-α, and iNOS produced by IFN-γ-polarized M1 macrophages. Immunofluorescence analysis showed that iron also reduced iNOS production. However, iron did not compromise but enhanced the ability of M1-polarized macrophages to phagocytose FITC-dextran. Moreover, we demonstrated that STAT1 inhibition was required for reduction of iNOS and M1-related cytokines production by the present of iron. Together, these findings indicated that iron decreased polarization of M1 macrophages and inhibited the production of the proinflammatory cytokines. The results expanded our knowledge about the role of iron in macrophage polarization.

  8. In vitro studies of interaction of rickettsia and macrophages: effect of ultraviolet light on Coxiella burnetti inactivation and macrophage enzymes

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.S.; Kishimoto, R.A.; Canonico, P.G.

    1980-03-01

    The inactivation of Coxiella burnetii in suspension or in cultures of guinea pig peritoneal macrophages by ultraviolet (uv) light was studied. The effect of uv treatment on the activity of macrophage organelle marker enzymes and their subsequent equilibration in linear sucrose gradients was also determined. It was shown that uv treatment for 15 s at a distance of 10 cm inactivated C. burnetti, either in suspension or within guinea pig peritoneal macrophages. Similar uv treatment had little effect on the activity or equilibration of macrophage organelle marker enzymes in linear sucrose gradients.

  9. Dakin Solution Alters Macrophage Viability and Function

    Science.gov (United States)

    2014-07-18

    a major clone in cystic fibrosis patients and aquatic habitats. J Bacteriol 1996;178:85. [31] Qiu H, KuoLee R, Harris G, Van Rooijen N, Patel GB, Chen...injury and inflammation, whereas the M2 macrophage is associated with tissue repair and fibrosis [25]. In the inflammatory phase of wound healing...Tiwari VK, Narayanan RP. Fungal infections in burns: diagnosis and management. Indian J Plast Surg 2010;43(Suppl l):S37. [11] Fleming A. The action of

  10. Polyglucose nanoparticles with renal elimination and macrophage avidity facilitate PET imaging in ischaemic heart disease

    NARCIS (Netherlands)

    Keliher, Edmund J.; Ye, Yu-Xiang; Wojtkiewicz, Gregory R.; Aguirre, Aaron D.; Tricot, Benoit; Senders, Max L.; Groenen, Hannah; Fay, Francois; Perez-Medina, Carlos; Calcagno, Claudia; Carlucci, Giuseppe; Reiner, Thomas; Sun, Yuan; Courties, Gabriel; Iwamoto, Yoshiko; Kim, Hye-Yeong; Wang, Cuihua; Chen, John W.; Swirski, Filip K.; Wey, Hsiao-Ying; Hooker, Jacob; Fayad, Zahi A.; Mulder, Willem J. M.; Weissleder, Ralph; Nahrendorf, Matthias

    2017-01-01

    Tissue macrophage numbers vary during health versus disease. Abundant inflammatory macrophages destruct tissues, leading to atherosclerosis, myocardial infarction and heart failure. Emerging therapeutic options create interest in monitoring macrophages in patients. Here we describe positron emission

  11. Multiple pathway assessment to predict anti-atherogenic efficacy of drugs targeting macrophages in atherosclerotic plaques

    NARCIS (Netherlands)

    Alaarg, Amr Muhmed Sabry Abdelhakeem; Zheng, K.H.; van der Valk, F.M.; Eduardo Da Silva, Acarilia; Versloot, M.; Quarles van Ufford, Linda C.; Schulte, D.M.; Storm, Gerrit; Metselaar, Josbert Maarten; Stroes, E.S.; Hamers, A.A.J.

    2016-01-01

    Background Macrophages play a central role in atherosclerosis development and progression, hence, targeting macrophage activity is considered an attractive therapeutic. Recently, we documented nanomedicinal delivery of the anti-inflammatory compound prednisolone to atherosclerotic plaque macrophages

  12. Beryllium-stimulated apoptosis in macrophage cell lines.

    Science.gov (United States)

    Sawyer, R T; Fadok, V A; Kittle, L A; Maier, L A; Newman, L S

    2000-08-21

    In vitro stimulation of bronchoalveolar lavage cells from patients with chronic beryllium disease (CBD) induces the production of TNF-alpha. We tested the hypothesis that beryllium (Be)-stimulated TNF-alpha might induce apoptosis in mouse and human macrophage cell lines. These cell lines were selected because they produce a range of Be-stimulated TNF-alpha. The mouse macrophage cell line H36.12j produces high levels of Be-stimulated TNF-alpha. The mouse macrophage cell line P388D.1 produces low, constitutive, levels of TNF-alpha and does not up-regulate Be-stimulated TNF-alpha production. The DEOHS-1 human CBD macrophage cell line does not produce constitutive or Be-stimulated TNF-alpha. Apoptosis was determined by microscopic observation of propidium iodide stained fragmented nuclei in unstimulated and BeSO(4)-stimulated macrophage cell lines. BeSO(4) induced apoptosis in all macrophage cell lines tested. Beryllium-stimulated apoptosis was dose-responsive and maximal after 24 h of exposure to 100 microM BeSO(4). In contrast, unstimulated and Al(2)(SO(4))(3)-stimulated macrophage cell lines did not undergo apoptosis. The general caspase inhibitor BD-fmk inhibited Be-stimulated macrophage cell line apoptosis at concentrations above 50 microM. Our data show that Be-stimulated macrophage cell line apoptosis was caspase-dependent and not solely dependent on Be-stimulated TNF-alpha levels. We speculate that the release of Be-antigen from apoptotic macrophages may serve to re-introduce Be material back into the lung microenvironment, make it available for uptake by new macrophages, and thereby amplify Be-stimulated cytokine production, promoting ongoing inflammation and granuloma maintenance in CBD.

  13. Zinc intervention on macrophages and lymphocytes responce

    Energy Technology Data Exchange (ETDEWEB)

    Lastra, M.D.; Pastelin, R.; Camacho, A.; Monroy, B.; Aguilar, A.E. [Lab. de Investigacion en Immunologia, Univ. Nacional Autonoma de Mexico (Mexico)

    2001-07-01

    Normal zinc levels are essential for the development and maintenance of immune functions; Zn deficiency is detrimental to the embryo and offspring of experimental animals, especially concerning immune development. It is known that Zn supplementation improves immune responses. To further explore the relation between Zn administration and the metal in vitro effects, we studied zinc (500 mg/l) supplementation impact on lymphocytes and macrophages and zinc in vitro effects, in BALB/c mice supplemented from gestation to lactation. Results show a significant increase in proliferation (assessed by {sup 3}H incorporation) in lymphocytes exposed to Zn (0.1 mM) in vitro, in 3-wk-old mice; this effect is annulled when the supplementation period is lengthened, indicating saturation of the mechanisms involved in zinc induced stimulation. Macrophages functional capacity assessed by erythrophagocytosis was also improved by Zn supplementation and furthermore by the in vitro exposure to the metal, in mice 3 wk old, this was also depressed by Zn accumulation due to the supplementation period extension (9 weeks). Results show an improvement in the immune parameters analysed due to zinc supplementation and to zinc in vitro exposure. Results also suggest the accumulation of zinc as a result of prolonged supplementation periods, suppresses the cells response to zinc in vitro. (orig.)

  14. Selective phosphorylation during early macrophage differentiation

    KAUST Repository

    Zhang, Huoming

    2015-08-26

    The differentiation of macrophages from monocytes is a tightly controlled and complex biological process. Although numerous studies have been conducted using biochemical approaches or global gene/gene profiling, the mechanisms of the early stages of differentiation remain unclear. Here we used SILAC-based quantitative proteomics approach to perform temporal phosphoproteome profiling of early macrophage differentiation. We identified a large set of phosphoproteins and grouped them as PMA-regulated and non-regulated phosphoproteins in the early stages of differentiation. Further analysis of the PMA-regulated phosphoproteins revealed that transcriptional suppression, cytoskeletal reorganization and cell adhesion were among the most significantly activated pathways. Some key involved regulators of these pathways are mTOR, MYB, STAT1 and CTNNB. Moreover, we were able to classify the roles and activities of several transcriptional factors during different differentiation stages and found that E2F is likely to be an important regulator during the relatively late stages of differentiation. This study provides the first comprehensive picture of the dynamic phosphoproteome during myeloid cells differentiation, and identifies potential molecular targets in leukemic cells.

  15. Notch Regulates Macrophage-Mediated Inflammation in Diabetic Wound Healing

    Directory of Open Access Journals (Sweden)

    Andrew S. Kimball

    2017-06-01

    Full Text Available Macrophages are essential immune cells necessary for regulated inflammation during wound healing. Recent studies have identified that Notch plays a role in macrophage-mediated inflammation. Thus, we investigated the role of Notch signaling on wound macrophage phenotype and function during normal and diabetic wound healing. We found that Notch receptor and ligand expression are dynamic in wound macrophages during normal healing. Mice with a myeloid-specific Notch signaling defect (DNMAMLfloxedLyz2Cre+ demonstrated delayed early healing (days 1–3 and wound macrophages had decreased inflammatory gene expression. In our physiologic murine model of type 2 diabetes (T2D, Notch receptor expression was significantly increased in wound macrophages on day 6, following the initial inflammatory phase of wound healing, corresponding to increased inflammatory cytokine expression. This increase in Notch1 and Notch2 was also observed in human monocytes from patients with T2D. Further, in prediabetic mice with a genetic Notch signaling defect (DNMAMLfloxedLyz2Cre+ on a high-fat diet, improved wound healing was seen at late time points (days 6–7. These findings suggest that Notch is critical for the early inflammatory phase of wound healing and directs production of macrophage-dependent inflammatory mediators. These results identify that canonical Notch signaling is important in directing macrophage function in wound repair and define a translational target for the treatment of non-healing diabetic wounds.

  16. Effect of Cadmium on Macrophage U937 Cell Proliferation and ...

    African Journals Online (AJOL)

    Later, U937 cells were also pre-treated with phorbol 12- myristate, 13-acetate to transform the cells from the monocyte-like morphology to the macrophage form. The macrophage U937 cells were then incubated with different concentrations of cadmium and the supernatants of the cell cultures were analyzed for the ...

  17. Human macrophage polarization in vitro: Maturation and activation methods compared

    NARCIS (Netherlands)

    Vogel, D.Y.S.; Glim, J.E.; Stavenuiter, A.W.D.; Breur, M.; Heijnen, P.; Amor, S.; Dijkstra, C.D.; Beelen, R.H.J.

    2014-01-01

    Macrophages form a heterogeneous cell population displaying multiple functions, and can be polarized into pro- (M1) or anti-inflammatory (M2) macrophages, by environmental factors. Their activation status reflects a beneficial or detrimental role in various diseases. Currently several in vitro

  18. Consistent inhibition of cyclooxygenase drives macrophages towards the inflammatory phenotype.

    Directory of Open Access Journals (Sweden)

    Yi Rang Na

    Full Text Available Macrophages play important roles in defense against infection, as well as in homeostasis maintenance. Thus alterations of macrophage function can have unexpected pathological results. Cyclooxygenase (COX inhibitors are widely used to relieve pain, but the effects of long-term usage on macrophage function remain to be elucidated. Using bone marrow-derived macrophage culture and long-term COX inhibitor treatments in BALB/c mice and zebrafish, we showed that chronic COX inhibition drives macrophages into an inflammatory state. Macrophages differentiated in the presence of SC-560 (COX-1 inhibitor, NS-398 (COX-2 inhibitor or indomethacin (COX-1/2 inhibitor for 7 days produced more TNFα or IL-12p70 with enhanced p65/IκB phosphoylation. YmI and IRF4 expression was reduced significantly, indicative of a more inflammatory phenotype. We further observed that indomethacin or NS-398 delivery accelerated zebrafish death rates during LPS induced sepsis. When COX inhibitors were released over 30 days from an osmotic pump implant in mice, macrophages from peritoneal cavities and adipose tissue produced more TNFα in both the basal state and under LPS stimulation. Consequently, indomethacin-exposed mice showed accelerated systemic inflammation after LPS injection. Our findings suggest that macrophages exhibit a more inflammatory phenotype when COX activities are chronically inhibited.

  19. Biomaterials Influence Macrophage-Mesenchymal Stem Cell Interaction In Vitro

    NARCIS (Netherlands)

    N. Grotenhuis (Nienke); S.F. De Witte (Samantha Fh); G.J.V.M. van Osch (Gerjo); Y. Bayon (Yves); J.F. Lange (Johan); Y.M. Bastiaansen-Jenniskens (Yvonne)

    2016-01-01

    textabstractBackground: Macrophages and mesenchymal stem cells (MSCs) are important cells in wound healing. We hypothesized that the cross-talk between macrophages and adipose tissue-derived MSCs (ASCs) is biomaterial dependent, thereby influencing processes involved in wound healing. Materials and

  20. serrulatus Venom on Murine Macrophage Functions in Vitro

    Directory of Open Access Journals (Sweden)

    Vera L. Petricevich

    2005-01-01

    highest levels of IL-1α, IL-β, and TNF were observed after 12 hours and that (b the maximum levels of IFN-γ and NO were observed after 72 hours. Taken together, these data indicate that fractions have a differential immunomodulating effect on macrophage secretion, and that FII is a potent activator of TNF production of macrophages.

  1. Of macrophages and red blood cells; a complex love story.

    Directory of Open Access Journals (Sweden)

    Djuna Zoe de Back

    2014-01-01

    Full Text Available Macrophages tightly control the production and clearance of red blood cells (RBC. During steady state haematopoiesis, approximately 1010 red blood cells are produced per hour within erythroblastic islands in humans. In these erythroblastic islands, resident bone marrow macrophages provide erythroblasts with interactions that are essential for erythroid development. New evidence suggests that not only under homeostasis but also under stress conditions, macrophages play an important role in promoting erythropoiesis. Once RBC have matured, these cells remain in circulation for about 120 days. At the end of their life span, RBC are cleared by macrophages residing in the spleen and the liver. Current theories about the removal of senescent RBC and the essential role of macrophages will be discussed as well as the role of macrophages in facilitating the removal of damaged cellular content from the RBC. In this review we will provide an overview on the role of macrophages in the regulation of RBC production, maintenance and clearance. In addition, we will discuss the interactions between these two cell types during transfer of immune complexes and pathogens from RBC to macrophages.

  2. Macrophages are critical effectors of antibody therapies for cancer.

    Science.gov (United States)

    Weiskopf, Kipp; Weissman, Irving L

    2015-01-01

    Macrophages are innate immune cells that derive from circulating monocytes, reside in all tissues, and participate in many states of pathology. Macrophages play a dichotomous role in cancer, where they promote tumor growth but also serve as critical immune effectors of therapeutic antibodies. Macrophages express all classes of Fcγ receptors, and they have immense potential to destroy tumors via the process of antibody-dependent phagocytosis. A number of studies have demonstrated that macrophage phagocytosis is a major mechanism of action of many antibodies approved to treat cancer. Consequently, a number of approaches to augment macrophage responses to therapeutic antibodies are under investigation, including the exploration of new targets and development of antibodies with enhanced functions. For example, the interaction of CD47 with signal-regulatory protein α (SIRPα) serves as a myeloid-specific immune checkpoint that limits the response of macrophages to antibody therapies, and CD47-blocking agents overcome this barrier to augment phagocytosis. The response of macrophages to antibody therapies can also be enhanced with engineered Fc variants, bispecific antibodies, or antibody-drug conjugates. Macrophages have demonstrated success as effectors of cancer immunotherapy, and further investigation will unlock their full potential for the benefit of patients.

  3. DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas

    DEFF Research Database (Denmark)

    Herrtwich, Laura; Nanda, Indrajit; Evangelou, Konstantinos

    2016-01-01

    granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not, as previously thought, by cell-to-cell fusion. TLR2 signaling promoted macrophage polyploidy and suppressed genomic instability by regulating Myc and ATR. We propose that, in the presence of persistent...

  4. Epigenetic pathways in macrophages emerge as novel targets in atherosclerosis

    NARCIS (Netherlands)

    Neele, Annette E.; van den Bossche, Jan; Hoeksema, Marten A.; de Winther, Menno P. J.

    2015-01-01

    Atherosclerosis is a lipid-driven chronic inflammatory disorder. Monocytes and macrophages are key immune cells in the development of disease and clinical outcome. It is becoming increasingly clear that epigenetic pathways govern many aspects of monocyte and macrophage differentiation and

  5. Secretory products of macrophages: twenty-five years on

    OpenAIRE

    Nathan, Carl

    2012-01-01

    No longer do scientists look down on macrophages as “garbage men” that act “nonspecifically.” Last fall’s Nobel Prizes honored two of the few scientists who studied macrophages three decades ago. Now perhaps thousands do, and the subtypes they describe reflect ongoing discoveries of macrophages’ extraordinary plasticity.

  6. Cytokine expression of macrophages in HIV-1-associated vacuolar myelopathy.

    Science.gov (United States)

    Tyor, W R; Glass, J D; Baumrind, N; McArthur, J C; Griffin, J W; Becker, P S; Griffin, D E

    1993-05-01

    Macrophages are frequently present within the periaxonal and intramyelinic vacuoles that are located primarily in the posterior and lateral funiculi of the thoracic spinal cord in HIV-associated vacuolar myelopathy. But the role of these macrophages in the formation of the vacuoles is unclear. One hypothesis is that cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor (TNF)-alpha, are produced locally by macrophages and have toxic effects on myelin or oligodendrocytes. The resulting myelin damage eventually culminates in the removal of myelin by macrophages and vacuole formation. We studied thoracic spinal cord specimens taken at autopsy from HIV-positive (+) and HIV-negative individuals. The predominant mononuclear cells present in HIV+ spinal cords are macrophages. They are located primarily in the posterior and lateral funiculi regardless of the presence or absence of vacuolar myelopathy. Macrophages and microglia are more frequent in HIV+ than HIV-negative individuals and these cells frequently stain for class I and class II antigens, IL-1, and TNF-alpha. Activated macrophages positive for IL-1 and TNF-alpha are great increased in the posterior and lateral funiculi of HIV+ individuals with and without vacuolar myelopathy, suggesting they are present prior to the development of vacuoles. Cytokines, such as TNF-alpha, may be toxic for myelin or oligodendrocytes, leading to myelin damage and removal by macrophages and vacuole formation.

  7. Effect of Surface Modification and Macrophage Phenotype on Particle Internalization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daniel [Iowa State University; Phan, Ngoc [Iowa State University; Isely, Christopher [Iowa State University; Bruene, Lucas [Iowa State University; Bratlie, Kaitlin M [Ames Laboratory

    2014-11-10

    Material properties play a key role in the cellular internalization of polymeric particles. In the present study, we have investigated the effects of material characteristics such as water contact angle, zeta potential, melting temperature, and alternative activation of complement on particle internalization for pro-inflammatory, pro-angiogenic, and naïve macrophages by using biopolymers (~600 nm), functionalized with 13 different molecules. Understanding how material parameters influence particle internalization for different macrophage phenotypes is important for targeted delivery to specific cell populations. Here, we demonstrate that material parameters affect the alternative pathway of complement activation as well as particle internalization for different macrophage phenotypes. Here, we show that the quantitative structure–activity relationship method (QSAR) previously used to predict physiochemical properties of materials can be applied to targeting different macrophage phenotypes. These findings demonstrated that targeted drug delivery to macrophages could be achieved by exploiting material parameters.

  8. Polymer particle shape independently influences binding and internalization by macrophages.

    Science.gov (United States)

    Sharma, Gaurav; Valenta, David T; Altman, Yoav; Harvey, Sheryl; Xie, Hui; Mitragotri, Samir; Smith, Jeffrey W

    2010-11-01

    The interaction of macrophages with micro and nanoparticles (MNPs) is important because these cells clear particles from the circulation, and because they are potential therapeutic targets in inflammatory conditions, atherosclerosis and cancer. Therefore, an understanding of the features of MNPs that influence their interaction with macrophages may allow optimization of their properties for enhanced drug delivery. In this study, we show that particle shape impacts phagocytosis by macrophages, and more importantly, that particle shape and size separately impact attachment and internalization. The study provides a methodology for further exploring how particle shape can be controlled to achieve desired attachment and internalization. The results of the study also give mechanistic guidance on how particle shape can be manipulated to design drug carriers to evade macrophages, or alternatively to target macrophages. Copyright © 2010 Elsevier B.V. All rights reserved.

  9. Siderocalin inhibits the intracellular replication of Mycobacterium tuberculosis in macrophages

    DEFF Research Database (Denmark)

    Johnson, Erin E; Srikanth, Chittur V; Sandgren, Andreas

    2010-01-01

    that siderocalin expression is upregulated following M.tb infection of mouse macrophage cell lines and primary murine alveolar macrophages. Furthermore, siderocalin added exogenously as a recombinant protein or overexpressed in the RAW264.7 macrophage cell line inhibited the intracellular growth of the pathogen......Siderocalin is a secreted protein that binds to siderophores to prevent bacterial iron acquisition. While it has been shown to inhibit the growth of Mycobacterium tuberculosis (M.tb) in extracellular cultures, its effect on this pathogen within macrophages is not clear. Here, we show....... A variant form of siderocalin, which is expressed only in the macrophage cytosol, inhibited intracellular M.tb growth as effectively as the normal, secreted form, an observation that provides mechanistic insight into how siderocalin might influence iron acquisition by the bacteria in the phagosome. Our...

  10. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility.

    Science.gov (United States)

    Muller, Paul Andrew; Koscsó, Balázs; Rajani, Gaurav Manohar; Stevanovic, Korey; Berres, Marie-Luise; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Li, Xiu-Min; Mucida, Daniel; Stanley, E Richard; Dahan, Stephanie; Margolis, Kara Gross; Gershon, Michael David; Merad, Miriam; Bogunovic, Milena

    2014-07-17

    Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that, in the steady state, muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven crosstalk between muscularis macrophages and enteric neurons that controls gastrointestinal motility. PAPERFLICK: Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Crosstalk between Muscularis Macrophages and Enteric Neurons Regulates Gastrointestinal Motility

    Science.gov (United States)

    Muller, Paul Andrew; Koscsó, Balázs; Rajani, Gaurav Manohar; Stevanovic, Korey; Berres, Marie-Luise; Hashimoto, Daigo; Mortha, Arthur; Leboeuf, Marylene; Li, Xiu-Min; Mucida, Daniel; Stanley, E. Richard; Dahan, Stephanie; Margolis, Kara Gross; Gershon, Michael David; Merad, Miriam; Bogunovic, Milena

    2014-01-01

    SUMMARY Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that in the steady state muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven, crosstalk between muscularis macrophages and enteric neurons, which controls gastrointestinal motility. PMID:25036630

  12. Engineering mechanical microenvironment of macrophage and its biomedical applications.

    Science.gov (United States)

    Li, Jing; Li, Yuhui; Gao, Bin; Qin, Chuanguang; He, Yining; Xu, Feng; Yang, Hui; Lin, Min

    2018-03-01

    Macrophages are the most plastic cells in the hematopoietic system and can be widely found in almost all tissues. Recently studies have shown that mechanical cues (e.g., matrix stiffness and stress/strain) can significantly affect macrophage behaviors. Although existing reviews on the physical and mechanical cues that regulate the macrophage's phenotype are available, engineering mechanical microenvironment of macrophages in vitro as well as a comprehensive overview and prospects for their biomedical applications (e.g., tissue engineering and immunotherapy) has yet to be summarized. Thus, this review provides an overview on the existing methods for engineering mechanical microenvironment of macrophages in vitro and then a section on their biomedical applications and further perspectives are presented.

  13. Therapeutic potential of carbohydrates as regulators of macrophage activation.

    Science.gov (United States)

    Lundahl, Mimmi L E; Scanlan, Eoin M; Lavelle, Ed C

    2017-12-15

    It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal "classically activated" M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial - for example the successful introduction of biomedical implants. Although there are numerous endogenous and exogenous factors that have an impact on the macrophage polarisation spectrum, this review will focus specifically on prominent macrophage-modulating carbohydrate motifs with a view towards highlighting structure-function relationships and therapeutic potential. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Macrophages Contribute to the Spermatogonial Niche in the Adult Testis

    Directory of Open Access Journals (Sweden)

    Tony DeFalco

    2015-08-01

    Full Text Available The testis produces sperm throughout the male reproductive lifespan by balancing self-renewal and differentiation of spermatogonial stem cells (SSCs. Part of the SSC niche is thought to lie outside the seminiferous tubules of the testis; however, specific interstitial components of the niche that regulate spermatogonial divisions and differentiation remain undefined. We identified distinct populations of testicular macrophages, one of which lies on the surface of seminiferous tubules, in close apposition to areas of tubules enriched for undifferentiated spermatogonia. These macrophages express spermatogonial proliferation- and differentiation-inducing factors, such as colony-stimulating factor 1 (CSF1 and enzymes involved in retinoic acid (RA biosynthesis. We show that transient depletion of macrophages leads to a disruption in spermatogonial differentiation. These findings reveal an unexpected role for macrophages in the spermatogonial niche in the testis and raise the possibility that macrophages play previously unappreciated roles in stem/progenitor cell regulation in other tissues.

  15. The current status of autologous blood transfusion in Japan--the importance of pre-deposit autologous blood donation program and the needs to achieve patient blood management.

    Science.gov (United States)

    Tsuno, Nelson Hirokazu; Nagura, Yutaka; Kawabata, Michiru; Matsuhashi, Mika; Sone, Shinji; Ikeda, Toshiyuki; Okochi, Naoko; Takahashi, Koki

    2013-12-01

    Autologous blood transfusion (ABT) is currently considered the safest transfusion, since the risks of allogeneic immunological reaction and viral transmission are theoretically null. Although its use has declined in Western countries in the recent decade, it has been progressively expanded in Japan. With the widening of the concept of patient blood management (PBM), which aims to prevent the harmful adverse effects of the exposure to allogeneic blood, the importance of the ABT has once again gained interest. Here, we retrospectively analyzed the cases pre-depositing autologous blood for an elective surgery in the period of January 2000 to December 2010 in our hospital, where a pre-deposit autologous blood donation (PAD) program has been established in 2006, in an attempt to analyze the improvements achieved, and the problems remaining to achieve patient blood management. The PAD program contributed for the further improvement of ABT, and the number of participating patients increased, especially in the period 2002-2003, when the idea of PAD program implementation came out. By simple extrapolation of the ABT data to allogeneic blood, ABT was found to be superior in terms of cost-effectiveness. However, problems such as the high wastage rate, and the inappropriate transfusion triggers remain to be solved. ABT plays the central role in PBM, but to achieve the real PBM, there is need to indicate ABT appropriately, according to the individual needs, and use it adequately, without discarding. Our present data reflect the present status of the ABT performance in Japan, and will serve as the basis for the development of strategies to achieve safe and appropriate performance of ABT, and consequently, achieve PBM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Usefulness of concomitant autologous blood and dextranomer/hyaluronic acid copolymer injection to correct vesicoureteral reflux.

    Science.gov (United States)

    Kajbafzadeh, Abdol-Mohammad; Tourchi, Ali

    2012-09-01

    We present the long-term results of a new modification of endoscopic treatment of vesicoureteral reflux involving concomitant injection of autologous blood following the standard hydrodistention injection technique to prevent bulking agent leakage immediately after the procedure. A total of 341 children underwent endoscopic implantation of dextranomer/hyaluronic acid for vesicoureteral reflux. A subset of 171 patients underwent hydrodistention autologous blood injection, while 170 underwent classic hydrodistention injection. Frequency of symptomatic urinary tract infection after endoscopic treatment was recorded. Success was defined as absence of vesicoureteral reflux on postoperative voiding cystourethrography. A total of 523 ureters in 214 girls and 127 boys were treated. In patients undergoing hydrodistention autologous blood injection mean age was 39.48 months, mean maximal reflux grade was 3.02 and success rate was 93.6% after the first injection (98.0% in patients with grade II, 92.1% with grade III, 93.3% with grade IV and 85.7% with grade V reflux). In patients who underwent classic hydrodistention injection mean age was 36.12 months, mean maximal reflux grade 3.05 and success rate was 81.8% after the first injection (91.5% in patients with grade II, 89.4% with grade III, 74.4% with grade IV and 44.4% with grade V reflux). The success rate was significantly higher (p = 0.001) in patients undergoing hydrodistention autologous blood injection vs classic hydrodistention injection. Of the patients 1.7% in the hydrodistention autologous blood injection group and 2.9% in the classic hydrodistention injection group reported symptomatic urinary tract infection during followup. Immediate injection of autologous blood following dextranomer/hyaluronic acid injection to create a blood clot and barricade against bulking agent leakage is more effective than pure dextranomer/hyaluronic acid implantation. This novel modification stabilizes the subureteral implant mount and

  17. Macrophage Sortilin Promotes LDL Uptake, Foam Cell Formation, and Atherosclerosis

    Science.gov (United States)

    Patel, Kevin M.; Strong, Alanna; Tohyama, Junichiro; Jin, Xueting; Morales, Carlos R.; Billheimer, Jeffery; Millar, John; Kruth, Howard; Rader, Daniel J.

    2015-01-01

    Rationale Non-coding gene variants at the SORT1 locus are strongly associated with LDL-C levels as well as with coronary artery disease (CAD). SORT1 encodes a protein called sortilin, and hepatic sortilin modulates LDL metabolism by targeting apoB-containing lipoproteins to the lysosome. Sortilin is also expressed in macrophages, but its role in macrophage uptake of LDL and in atherosclerosis independent of plasma LDL-C levels is unknown. Objective To determine the effect of macrophage sortilin expression on LDL uptake, foam cell formation, and atherosclerosis. Methods and Results We crossed Sort1−/− mice onto a ‘humanized’ Apobec1−/−; hAPOB Tg background and determined that Sort1 deficiency on this background had no effect on plasma LDL-C levels but dramatically reduced atherosclerosis in the aorta and aortic root. In order to test whether this effect was a result of macrophage sortilin deficiency, we transplanted Sort1−/−;LDLR−/− or Sort1+/+;LDLR−/− bone marrow into Ldlr−/− mice and observed a similar reduction in atherosclerosis in mice lacking hematopoetic sortilin without an effect on plasma LDL-C levels. In an effort to determine the mechanism by which hematopoetic sortilin deficiency reduced atherosclerosis, we found no effect of sortilin deficiency on macrophage recruitment or LPS-induced cytokine release in vivo. In contrast, sortilin deficient macrophages had significantly reduced uptake of native LDL ex vivo and reduced foam cell formation in vivo, whereas sortilin overexpression in macrophages resulted in increased LDL uptake and foam cell formation. Conclusions Macrophage sortilin deficiency protects against atherosclerosis by reducing macrophage uptake of LDL. Sortilin-mediated uptake of native LDL into macrophages may be an important mechanism of foam cell formation and contributor to atherosclerosis development. PMID:25593281

  18. Autologous bone marrow mononuclear cell transplant and surgical decompression in a dog with chronic spinal cord injury.

    Science.gov (United States)

    Tamura, Katsutoshi; Harada, Yasuji; Kunimi, Maki; Takemitsu, Hiroshi; Hara, Yasushi; Nakamura, Tatsuo; Tagawa, Masahiro

    2015-02-01

    In dogs with deep analgesia caused by acute spinal cord injury from thoracolumbar disk herniation, autologous bone marrow mononuclear cell transplant may improve recovery. The purpose of the present study was to evaluate autologous bone marrow mononuclear cell transplant in a dog that had paraplegia and deep analgesia caused by chronic spinal cord injury. Autologous bone marrow mononuclear cell transplant was performed in a dog having paraplegia and analgesia for 3 years that was caused by a chronic spinal cord injury secondary to Hansen type I thoracolumbar disk herniation. Functional recovery was evaluated with electrophysiologic studies and the Texas Spinal Cord Injury Scale. Somatosensory evoked potentials were absent before transplant but were detected after transplant. Functional improvement was noted (Texas Spinal Cord Injury Scale: before transplant, 0; after transplant, 6). No adverse events were observed. Autologous bone marrow mononuclear cell transplant into the subarachnoid space may be a safe and beneficial treatment for chronic spinal cord injury in dogs.

  19. Imaging collagen remodeling and sensing transplanted autologous fibroblast metabolism in mouse dermis using multimode nonlinear optical imaging

    International Nuclear Information System (INIS)

    Zhuo Shuangmu; Chen Jianxin; Jiang Xingshan; Xie Shusen; Cao Ning; Xiong Shuyuan

    2008-01-01

    Collagen remodeling and transplanted autologous fibroblast metabolic states in mouse dermis after cellular injection are investigated using multimode nonlinear optical imaging. Our findings show that the technique can image the progress of collagen remodeling in mouse dermis. It can also image transplanted autologous fibroblasts in their collagen matrix environment in the dermis, because of metabolic activity. It was also found that the approach can provide two-photon ratiometric redox fluorometry based on autologous fibroblast fluorescence from reduced nicotinamide adenine dinucleotide coenzyme and oxidized flavoproteins for sensing the autologous fibroblast metabolic state. These results show that the multimode nonlinear optical imaging technique may have potential in a clinical setting as an in vivo diagnostic and monitoring system for cellular therapy in plastic surgery

  20. MR cartilage imaging in assessment of the regenerative power of autologous peripheral blood stem cell injection in knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Khaled A. Ahmad

    2014-09-01

    Conclusion: Limited good level of evidence showed that repeated intra-articular injections of autologous PBSC resulted in an improvement of the quality of articular cartilage repair and physical function as observed by MRI and clinical assessment.

  1. Bone regeneration using the freshly isolated autologous stromal vascular fraction of adipose tissue in combination with calcium phosphate ceramics

    NARCIS (Netherlands)

    Prins, H.J.; Schulten, E.A.J.M.; ten Bruggenkate, C.M.; Klein-Nulend, J.; Helder, M.N.

    2016-01-01

    In patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement, bone substitutes are currently evaluated as alternatives for autologous bone. However, bone substitutes have only osteoconductive properties and lack osteoinductive potential. Therefore, this phase I study

  2. Macrophage-Derived Protein S Facilitates Apoptotic Polymorphonuclear Cell Clearance by Resolution Phase Macrophages and Supports Their Reprogramming.

    Science.gov (United States)

    Lumbroso, Delphine; Soboh, Soaad; Maimon, Avi; Schif-Zuck, Sagie; Ariel, Amiram; Burstyn-Cohen, Tal

    2018-01-01

    The complete resolution of inflammation requires the uptake of apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and the consequent reprogramming of the engulfing phagocytes to reparative and pro-resolving phenotypes. The tyrosine kinase receptors TYRO3, AXL, and MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses and efferocytosis. Protein S (PROS1) is a ligand for all TAM receptors that mediates various aspects of their activity. However, the involvement of PROS1 in the resolution of inflammation is incompletely understood. Here, we report the upregulation of Pros1 in macrophages during the resolution of inflammation. Selective knockout of Pros1 in the myeloid lineage significantly downregulated macrophage pro-resolving properties. Hence, Pros1 -deficient macrophages engulfed fewer apoptotic PMN remnants in vivo , and exogenous PROS1 rescued impaired efferocytosis ex vivo . Moreover, Pros1 -deficient peritoneal macrophages secreted higher levels of the pro-inflammatory mediators TNFα and CCL3, while they secreted lower levels of the reparative/anti-inflammatory IL-10 following exposure to lipopolysaccharide in comparison to their WT counterparts. Moreover, Pros1 -deficient macrophages expressed less of the anti-inflammatory/pro-resolving enzymes arginase-1 and 12/15-lipoxygenase and produced less of the specialized pro-resolving mediator resolvin D1. Altogether, our results suggest that macrophage-derived PROS1 is an important effector molecule in regulating the efferocytosis, maturation, and reprogramming of resolution phase macrophages, and imply that PROS1 could provide a new therapeutic target for inflammatory and fibrotic disorders.

  3. DMPD: Differential responses of human monocytes and macrophages to IL-4 and IL-13. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10534111 Differential responses of human monocytes and macrophages to IL-4 and IL-1...):575-8. (.png) (.svg) (.html) (.csml) Show Differential responses of human monocytes and macrophages to IL-...4 and IL-13. PubmedID 10534111 Title Differential responses of human monocytes an

  4. DMPD: The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbiological mechanisms. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 10473535 The oxidation of lipoproteins by monocytes-macrophages. Biochemical andbio.... (.png) (.svg) (.html) (.csml) Show The oxidation of lipoproteins by monocytes-macrophages. Biochemical and...biological mechanisms. PubmedID 10473535 Title The oxidation of lipoproteins by m

  5. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Madaric, Juraj, E-mail: jurmad@hotmail.com [National Institute of Cardiovascular Diseases (NUSCH) and Slovak Medical University, Department of Cardiology and Angiology (Slovakia); Klepanec, Andrej [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia); Mistrik, Martin [Clinic of Hematology and Transfusiology, Faculty Hospital (Slovakia); Altaner, Cestmir [Slovak Academy of Science, Institute of Experimental Oncology (Slovakia); Vulev, Ivan [National Institute of Cardiovascular Diseases, Department of Diagnostic and Interventional Radiology (Slovakia)

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  6. Characteristics of Suppressor Macrophages Induced by Mycobacterial and Protozoal Infections in relation to Alternatively Activated M2 Macrophages

    Directory of Open Access Journals (Sweden)

    Haruaki Tomioka

    2012-01-01

    Full Text Available In the advanced stages of mycobacterial infections, host immune systems tend to change from a Th1-type to Th2-type immune response, resulting in the abrogation of Th1 cell- and macrophage-mediated antimicrobial host protective immunity. Notably, this type of immune conversion is occasionally associated with the generation of certain types of suppressor macrophage populations. During the course of Mycobacterium tuberculosis (MTB and Mycobacterium avium-intracellulare complex (MAC infections, the generation of macrophages which possess strong suppressor activity against host T- and B-cell functions is frequently encountered. This paper describes the immunological properties of M1- and M2-type macrophages generated in tumor-bearing animals and those generated in hosts with certain microbial infections. In addition, this paper highlights the immunological and molecular biological characteristics of suppressor macrophages generated in hosts with mycobacterial infections, especially MAC infection.

  7. SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ae Sin; Jung, Yu Jin; Kim, Dal; Nguyen-Thanh, Tung [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Kang, Kyung Pyo [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Lee, Sik [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Park, Sung Kwang [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of); Kim, Won, E-mail: kwon@jbnu.ac.kr [Department of Internal Medicine, Chonbuk National University Medical School, Jeonju (Korea, Republic of); Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju (Korea, Republic of)

    2014-08-08

    Highlights: • Knockout of SIRT2 attenuates lipopolysaccharide-induced iNOS expression. • Lipopolysaccharide-induced NO production is decreased in SIRT2 KO macrophage. • SIRT2 deficiency suppresses lipopolysaccharide-induced ROS production in macrophage. • M1-macrophage related factors are decreased in SIRT2 deficient cells. • SIRT2 deficiency decreases lipopolysaccharide-induced activation of NFκB. - Abstract: Introduction: SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear. Materials and methods: In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling. Results: SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation. Discussion: Our data suggested that

  8. The human macrophage system: activity and functional morphology.

    Science.gov (United States)

    Michna, H

    1988-01-01

    Macrophages of humans could be extracted in large numbers from the connective tissue using a newly developed, not particularly difficult method. These macrophages were compared with the peritoneal macrophages of mice using light-, scanning and transmission electron-microscopic methods. The sterility of the cell suspension and the high yield of macrophages has allowed the first in vitro study of histiocytes to take place, in contrast to the classic 'microexudate-coated surface method'. The activity of the human in comparison with peritoneal murine macrophages has been evaluated using numerous histochemical and immunological techniques. These methods prove a modulation of the macrophage activity of healthy humans and mice under exemplary conditions of extremely strenuous physical exercising, in accordance with earlier experimental findings on animals alone. The degenerative changes which occur under these experimental conditions in the skeletal muscular system show an invasion of cells of the immune system, which are integrated into an explanation of the increased activity of macrophages. These results find their place in a new theoretical concept supporting the general validity of the co-operation of macrophages and other cells of the immune system in pathological degeneration and regeneration processes in the skeletal muscular system. It has been shown that the increased activity of human and murine macrophages brought about by extreme strenuous physical exercising, insofar as one is able to order them into a progressive scheme of stress happenings, fit very well into the concepts of the 'alarm reaction' phase. The activity of macrophages proves to be sensitive to the mediators of tumours of mesenchymal origin, with respect to the initial stage of phagocytosis, to the further biochemical deterioration, to the cytotoxicity and to the amount of cells; this, however, is not able to halt the rapid growth of sarcoma in a long term experiment. The proof of a weakened

  9. [Platelet-rich plasma combined with autologous cancellous bone : An alternative therapy for persistent non-union?].

    Science.gov (United States)

    Hakimi, M; Jungbluth, P; Thelen, S; Betsch, M; Linhart, W; Flohé, S; Windolf, J; Wild, M

    2011-11-01

    In addition to a stabile osteosynthesis autologous cancellous bone graft remains an essential therapy option in persistent non-union. Despite this therapy regimen persistent non-union can occasionally occur. The aim of this study was to evaluate the treatment of persistent non-union with a combination of platelet-rich plasma (PRP) and autologous cancellous bone. In this prospective study 17 patients with persistent non-union of long bones were treated by a combination of PRP and autologous iliac crest bone. Inclusion criteria were a minimum of one previously failed cancellous bone transplantation and an atrophic non-union persisting for 6-14 months (mean 9 months). The patients were examined clinically and radiologically at intervals of 3, 6 and 9 months postoperatively. After an average time of 17 months (range 15-23 months) the patients were treated by a combination of PRP and autologous cancellous bone. In all cases the non-union was successfully treated and osseous bridging was found radiologically after an average of 5 months (range 4-7 months) without any complications. The combination of PRP and autologous cancellous bone appears to be a safe and effective method for treatment of persistent non-union. The use of PRP does not result in substantial additional costs. Allergies and graft versus host reactions are not expected because of the autologous origin.

  10. Comparison of the osteogenic potentials of autologous cultured osteoblasts and mesenchymal stem cells loaded onto allogeneic cancellous bone granules.

    Science.gov (United States)

    Kim, Seok-Jung; Chung, Yang-Guk; Lee, Yun-Kyoung; Oh, Il-Whan; Kim, Yong-Sik; Moon, Young-Seok

    2012-02-01

    We compared the bone regeneration potentials of autologous cultured osteoblasts and of bone-marrow-derived autologous MSCs in combination with allogeneic cancellous bone granules in a rabbit radial defect model. Radial shaft defects over 15 mm were made in 26 New Zealand white rabbits. The animals underwent insertion of allogeneic cancellous bone granules containing autologous osteoblasts into right-side defects (the experimental group) and of allogeneic cancellous bone granules with autologous MSCs into left-side defects (the control group). To quantitatively assess bone regeneration, radiographic evaluations as well as BMD and BMC measurements were performed 3, 6, 9 and 12 weeks post-implantation and histology as well as micro-CT image analysis were performed at 6 and 12 weeks. Radiographic evaluations 3 weeks post-implantation showed that the experimental group had a higher mean bone quantity index (p bone volume and surface area than the control sides (p bone formation in the experimental group. This in vivo study demonstrates that a combination of autologous osteoblasts and small-sized, allogeneic cancellous bone granules leads to more rapid bone regeneration than autologous MSCs and small-sized, allogeneic cancellous bone granules.

  11. Stability of simultaneously placed dental implants with autologous bone grafts harvested from the iliac crest or intraoral jaw bone.

    Science.gov (United States)

    Kang, Young-Hoon; Kim, Hyun-Min; Byun, June-Ho; Kim, Uk-Kyu; Sung, Iel-Yong; Cho, Yeong-Cheol; Park, Bong-Wook

    2015-12-30

    Jaw bone and iliac bone are the most frequently used autologous bone sources for dental implant placement in patients with atrophic alveolar ridges. However, the comparative long-term stability of these two autologous bone grafts have not yet been investigated. The aim of this study was to compare the stability of simultaneously placed dental implants with autologous bone grafts harvested from either the iliac crest or the intraoral jaw bone for severely atrophic alveolar ridges. In total, 36 patients (21 men and 15 women) were selected and a retrospective medical record review was performed. We compared the residual increased bone height of the grafted bone, peri-implantitis incidence, radiological density in newly generated bones (HU values), and implant stability using resonance frequency analysis (ISQ values) between the two autologous bone graft groups. Both autologous bone graft groups (iliac bone and jaw bone) showed favorable clinical results, with similar long-term implant stability and overall implant survival rates. However, the grafted iliac bone exhibited more prompt vertical loss than the jaw bone, in particular, the largest vertical bone reduction was observed within 6 months after the bone graft. In contrast, the jaw bone graft group exhibited a slower vertical bone resorption rate and a lower incidence of peri-implantitis during long-term follow-up than the iliac bone graft group. These findings demonstrate that simultaneous dental implantation with the autologous intraoral jaw bone graft method may be reliable for the reconstruction of edentulous atrophic alveolar ridges.

  12. Histomorphometric Evaluation of Superovulation Effect on Follicular Development after Autologous Ovarian Transplantation in Mice

    Directory of Open Access Journals (Sweden)

    Amin Tamadon

    2015-01-01

    Full Text Available The effect of superovulation by pregnant mare serum gonadotropin (PMSG on autologous transplanted ovaries in the lumbar muscles of mice was histomorphometrically evaluated using the indices of number and volume of different kind of follicles and volume of corpora lutea, ovary, and stroma. Angiogenesis was observed after mouse ovarian transplantation on days 14 and 21 after ovarian grafting. After transplantation, the total number and volume of primary and secondary follicles reduced, while PMSG superovulation increased the total number and total volume of tertiary follicles and also the ovarian volume after transplantation. Transplantation increased the average size of primary, secondary, and tertiary follicles. Therefore, primary and secondary follicles can survive after autologous transplantation but their reservations diminished by increasing the time of transplantation. However, number of tertiary follicles and their response to superovulation increased over time after transplantation.

  13. Autologous bone marrow mononuclear cells transplant in patients with critical leg ischemia: preliminary clinical results.

    Science.gov (United States)

    Li, Min; Zhou, Hua; Jin, Xing; Wang, Mo; Zhang, Shiyi; Xu, Lei

    2013-10-01

    Stem cell transplant can induce vasculogenesis and improve the blood supply to an ischemic region, offering hope for chronic lower extremity ischemic diseases. Bone marrow mononuclear cells are one of the sources for stem cell transplants. We sought to observe the safety and efficacy of autologous bone marrow mononuclear cells transplant for treating critical limb ischemia. Eligible patients were randomized 1:1 to receive placebo (0.9% NaCl) or 1 × 107 piece/mL bone marrow mononuclear cell transplant. For 6 months, patients' skin ulcers, ankle-brachial index, and rest pain were examined and recorded before and after treatment. Six months after the bone marrow mononuclear cells transplant, clinical symptoms like rest pain and skin ulcers gradually abated (P transplant (P Autologous bone marrow mononuclear cells transplant for treatment of patients with chronic limb ischemia is safe, effective, and feasible.

  14. Autologous Fat Grafting in the Treatment of Painful Postsurgical Scar of the Oral Mucosa

    Directory of Open Access Journals (Sweden)

    Andrea Lisa

    2015-01-01

    Full Text Available Background. Persistent pain as a consequence of surgical treatment has been reported for several common surgical procedures and represents a clinical problem of great magnitude. Material and Methods. We describe the case of a 47-year-old female who presented a retractile scar that adhered to deep planes at the upper right of the vestibule due to surgical removal of maxillary exostosis, which determined important pain symptoms extending till the right shoulder during both chewing and rest. We subsequently treated her with autologous fat grafting according to Coleman’s technique. Results. Clinical assessments were performed at 5 and 14 days, 1, 3, and 6 months, and 1 year after surgical procedure. We observed a progressive release of scar retraction together with an important improvement of pain symptoms. Conclusion. The case described widens the possible application of autologous fat grafting on a new anatomical site as buccal vestibule and in one specific clinical setting confirming its promising biological effects.

  15. Improving oocyte quality by transfer of autologous mitochondria from fully grown oocytes

    DEFF Research Database (Denmark)

    Kristensen, Stine Gry; Pors, Susanne Elisabeth; Andersen, Claus Yding

    2017-01-01

    options using autologous mitochondria to potentially augment pregnancy potential in ART. Autologous transfer of mitochondria from the patient's own germline cells has attracted much attention as a possible new treatment to revitalize deficient oocytes. IVF births have been reported after transfer...... of oogonial precursor cell-derived mitochondria; however, the source and quality of the mitochondria are still unclear. In contrast, fully grown oocytes are loaded with mitochondria which have passed the genetic bottleneck and are likely to be of high quality. An increased supply of such oocytes could...... with high quality mitochondria can be obtained from natural or stimulated ovaries and potentially be used to improve both quality and quantity of oocytes available for fertility treatment....

  16. Autologous Platelet Concentrates as Treatment for Avascular Necrosis of Femoral Head in a Dog.

    Science.gov (United States)

    Parra, Estefanía; Vergara, Andrea; Silva, Raúl F

    2017-03-01

    Avascular necrosis of the femoral head is a developmental disturbance that generally affects young dogs of small breeds and produces ischemic necrosis of the femoral head resulting in an incongruous and malformed joint. The most common treatment is the excisional arthroplasty of the head and femoral neck. The aim of this study is to describe the treatment of avascular necrosis in a Yorkshire dog using intra-articular injections of autologous platelet concentrate. Evaluations were made at 0, 15, 30, 60, and 120 days of treatment, describing the following parameters: clinical gait analysis, perimetry, goniometry, and radiographic evaluations. The results obtained in this case suggest that the autologous platelet concentrate may be an alternative for the treatment of avascular necrosis of the femoral head in dogs. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. UPDATE ON THE ROLE OF AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA

    Directory of Open Access Journals (Sweden)

    Patrizia Tosi

    2012-11-01

    Full Text Available Autologous stem cell transplantation is considered the standard of care for multiple myeloma patients aged < 65 years with no relevant comorbidities. The addition of drugs acting both on bone marrow microenvironment and on neoplastic plasma cells has significantly increased the proportion of patients achieving a complete remission after induction therapy, and these results are mantained after high-dose melphalan, leading to a prolonged disease control. Studies are being carried out in order to evaluate whether short term consolidation or long-term maintenance therapy can result into disease eradication at the molecular level thus increasing also patients survival. The efficacy of these new drugs has raised the issue of deferring the transplant after achivng a second response upon relapse. Another controversial point is the optimal treatment strategy for high-risk patients, that do not benefit from autologous stem cell transplantation and for whom the efficacy of new drugs is still matter of debate.

  18. Regulatory challenges for autologous tissue engineered products on their way from bench to bedside in Europe.

    Science.gov (United States)

    Ram-Liebig, Gouya; Bednarz, Juergen; Stuerzebecher, Burkard; Fahlenkamp, Dirk; Barbagli, Guido; Romano, Giuseppe; Balsmeyer, Ulf; Spiegeler, Maria-Elsa; Liebig, Soeren; Knispel, Helmut

    2015-03-01

    Since the late eighties of last century the high potential of tissue engineered products (TEP)s has been shown for the treatment of various diseases and many scientific publications appeared in this field. However, only few products reached the market since. Development of TEPs is a promising but owing to its novelty a very challenging task that requires experts in this still developing field as well as ample financial resources. This paper summarises relevant regulatory challenges during quality, preclinical and clinical development of autologous TEPs in Europe. Selected strategies on how to manage major issues are presented, together with some examples from the development of an autologous TEP for urethroplasty. Considering these aspects may help other investigators with potential strategies during the development of novel TEPs. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Qualification of academic facilities for small-scale automated manufacture of autologous cell-based products.

    Science.gov (United States)

    Hourd, Paul; Chandra, Amit; Alvey, David; Ginty, Patrick; McCall, Mark; Ratcliffe, Elizabeth; Rayment, Erin; Williams, David J

    2014-01-01

    Academic centers, hospitals and small companies, as typical development settings for UK regenerative medicine assets, are significant contributors to the development of autologous cell-based therapies. Often lacking the appropriate funding, quality assurance heritage or specialist regulatory expertise, qualifying aseptic cell processing facilities for GMP compliance is a significant challenge. The qualification of a new Cell Therapy Manufacturing Facility with automated processing capability, the first of its kind in a UK academic setting, provides a unique demonstrator for the qualification of small-scale, automated facilities for GMP-compliant manufacture of autologous cell-based products in these settings. This paper shares our experiences in qualifying the Cell Therapy Manufacturing Facility, focusing on our approach to streamlining the qualification effort, the challenges, project delays and inefficiencies we encountered, and the subsequent lessons learned.

  20. Autologous human tissue-engineered heart valves: prospects for systemic application.

    Science.gov (United States)

    Mol, Anita; Rutten, Marcel C M; Driessen, Niels J B; Bouten, Carlijn V C; Zünd, Gregor; Baaijens, Frank P T; Hoerstrup, Simon P

    2006-07-04

    Tissue engineering represents a promising approach for the development of living heart valve replacements. In vivo animal studies of tissue-engineered autologous heart valves have focused on pulmonary valve replacements, leaving the challenge to tissue engineer heart valves suitable for systemic application using human cells. Tissue-engineered human heart valves were analyzed up to 4 weeks and conditioning using bioreactors was compared with static culturing. Tissue formation and mechanical properties increased with time and when using conditioning. Organization of the tissue, in terms of anisotropic properties, increased when conditioning was dynamic in nature. Exposure of the valves to physiological aortic valve flow demonstrated proper opening motion. Closure dynamics were suboptimal, most likely caused by the lower degree of anisotropy when compared with native aortic valve leaflets. This study presents autologous tissue-engineered heart valves based on human saphenous vein cells and a rapid degrading synthetic scaffold. Tissue properties and mechanical behavior might allow for use as living aortic valve replacements.

  1. Autologous stromal vascular fraction therapy for rheumatoid arthritis: rationale and clinical safety

    Directory of Open Access Journals (Sweden)

    Rodriguez Jorge

    2012-02-01

    Full Text Available Abstract Advancements in rheumatoid arthritis (RA treatment protocols and introduction of targeted biological therapies have markedly improved patient outcomes, despite this, up to 50% of patients still fail to achieve a significant clinical response. In veterinary medicine, stem cell therapy in the form of autologous stromal vascular fraction (SVF is an accepted therapeutic modality for degenerative conditions with 80% improvement and no serious treatment associated adverse events reported. Clinical translation of SVF therapy relies on confirmation of veterinary findings in targeted patient populations. Here we describe the rationale and preclinical data supporting the use of autologous SVF in treatment of RA, as well as provide 1, 3, 6, and 13 month safety outcomes in 13 RA patients treated with this approach.

  2. [Autologous stem cell transplantation for autoimmune diseases: recommendations from the SFGM-TC].

    Science.gov (United States)

    Farge, D; Terriou, L; Badoglio, M; Cras, A; Desreumaux, P; Hadj-Khelifa, S; Marjanovic, Z; Moisan, A; Dulery, R; Faucher, C; Hij, A; Martin, T; Vermersch, P; Yakoub-Agha, I

    2014-08-01

    Autologous hematopoietic stem cell transplantation is a valid alternative to immunosuppressive treatment in patients with auto-immune disease; however, the role of this approach remains subject to debate. In the attempt to harmonize clinical practices between different French transplantation centers, the French Society of Bone Marrow Transplantation and Cell Therapies (SFGM-TC) set up its fourth annual series of workshops which brought together practitioners from all of its member centers. These workshops took place in September 2013 in Lille. In this article we give an overview regarding the indications of autologous stem cell transplantation in auto-immune diseases as well as recommendations regarding post-transplant follow-up of patients. Copyright © 2014. Published by Elsevier SAS.

  3. Inflammatory Stroke Extracellular Vesicles Induce Macrophage Activation.

    Science.gov (United States)

    Couch, Yvonne; Akbar, Naveed; Davis, Simon; Fischer, Roman; Dickens, Alex M; Neuhaus, Ain A; Burgess, Annette I; Rothwell, Peter M; Buchan, Alastair M

    2017-08-01

    Extracellular vesicles (EVs) are protein-lipid complexes released from cells, as well as actively exocytosed, as part of normal physiology, but also during pathological processes such as those occurring during a stroke. Our aim was to determine the inflammatory potential of stroke EVs. EVs were quantified and analyzed in the sera of patients after an acute stroke (size, is significantly increased in stroke patients when compared to age-matched controls. Proteomic analysis reveals an overall increase in acute phase proteins, including C-reactive protein. EV fractions applied to monocyte-differentiated macrophage cultures induced inflammatory gene expression. Together these data show that EVs from stroke patients are proinflammatory in nature and are capable of inducing inflammation in immune cells. © 2017 American Heart Association, Inc.

  4. The macrophage scavenger receptor CD163

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Madsen, Mette; Møller, Holger J

    2006-01-01

    CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants...... are substantially expressed in blood, liver, and spleen, and the short tail variant is the predominant mRNA species. Using cell transfectants in which cDNA encoding the CD163 variants was inserted at the same site in the genome, we evaluated the expression and endocytic properties of the tail variants. Ligand...... uptake analysis showed that cells expressing the CD163 short tail variant exhibited a higher capacity for ligand endocytosis than cells expressing the CD163 long tail variants. The difference in endocytic activity was explained by confocal microscopic analysis, showing marked deviations in subcellular...

  5. Effect of storage xyloglucans on peritoneal macrophages.

    Science.gov (United States)

    Rosário, M M T; Noleto, G R; Bento, J F; Reicher, F; Oliveira, M B M; Petkowicz, C L O

    2008-01-01

    Xyloglucans from seeds of Copaifera langsdorffii (XGC), Hymenaea courbaril (XGJ) and Mucuna sloanei (XGM) were obtained from milled and defatted cotyledons by aqueous extraction at 25 degrees C. The resulting fractions contained Glc, Xyl and Gal in molar ratios of 2.5: 1.5: 1.0 (XGC), 3.8: 2.6: 1.0 (XGJ) and 2.5: 1.6: 1.0 (XGM). HPSEC-MALLS/RI analysis showed that each polysaccharide fraction was homogeneous; M(w) values were 1.6 x 10(5), 2.0 x 10(5) and 1.5 x 10(5)g/mol, respectively. The effect of the xyloglucans on the production of O(2)*(-) and NO* and on the recruitment of macrophages to the mouse peritoneum was evaluated. All polysaccharides promoted an increase in the number of peritoneal macrophages in a dose-dependent manner. The largest increase, of 576% in comparison to the control group, was elicited by XGJ at 200 mg/kg. The effect of XGC, XGJ and XGM on O(2)*(-) production, in the presence or absence of phorbol 12-myristate 13-acetate (PMA), was not statistically significant. For NO(.) production, the lowest concentration of XGC (10 microg/ml) gave rise to an increase of 262% when compared to the control group; the effect was dose-dependent, reaching 307% at 50 microg/ml. On the other hand, XGJ at a concentration of 50 microg/ml enhanced NO* production by 92%. XGM did not affect NO* production significantly. The results indicate that xyloglucans from C. langsdorffii, H. courbaril and M. sloanei have immunomodulatory activity.

  6. Exploring the use of expanded erythroid cells for autologous transfusion for anemia of prematurity.

    Science.gov (United States)

    Khodabux, Chantal M; van Hensbergen, Yvette; Slot, Manon C; Bakker-Verweij, Margreet; Giordano, Piero C; Brand, Anneke

    2013-12-01

    Autologous cord blood (CB) red blood cells (RBCs) can partly substitute transfusion needs in premature infants suffering from anemia. To explore whether expanded CB cells could provide additional autologous cells suitable for transfusion, we set up a simple one-step protocol to expand premature CB cells. CB buffy coat cells and isolated CD34-positive (CD34(pos) ) cells from premature and full-term CB and adult blood were tested with several combinations of growth factors while omitting xenogeneic proteins from the culture medium. Cell differentiation was analyzed serially during 21 days using flow cytometry, progenitor assays, and high-performance liquid chromatography. Expanded CB buffy coat cells resulted in a threefold higher number of erythroblasts than the isolated CD34(pos) cells. However, the RBCs contaminating the buffy coat remained present during the culture with uncertain quality. Premature and full-term CB CD34(pos) cells had similar fold expansion capacity and erythroid differentiation. With the use of interleukin-3, stem cell factor, and erythropoietin, the fold increases of all CD34(pos) cell sources were similar: CB 3942 ± 1554, adult peripheral mobilized blood 4702 ± 1826, and bone marrow (BM) 4143 ± 1908. The proportion of CD235a expression indicating erythroblast presence on Day 21 was slightly higher in the adult CD34(pos) cell sources: peripheral blood stem cells (96.7 ± 0.8%) and BM (98.9 ± 0.5%) compared to CB (87.7 ± 2.7%; p = 0.002). We were not able to induce further erythroid maturation in vitro. This explorative study showed that fairly pure autologous erythroid-expanded cell populations could be obtained by a simple culture method, which should be optimized. Future challenges comprise obtaining ex vivo enucleation of RBCs with the use of a minimal manipulating approach, which can add up to autologous RBCs derived from CB in the treatment of anemia of prematurity. © 2013 American Association of Blood Banks.

  7. Autologous stem-cell transplantation in Hodgkin’s lymphoma: analysis of a therapeutic option

    Directory of Open Access Journals (Sweden)

    Adriano de Moraes Arantes

    2011-06-01

    Full Text Available Objective: To report the clinical progress of patients with Hodgkin’slymphoma treated with autologous transplantation after failure orrelapse of first-line treatment with chemotherapy and/or radiationtherapy. Methods: The results of a retrospective analysis of 31patients submitted to autologous transplantation as second-linetreatment, between April 2000 and December 2008, were analyzed.Fourteen men and seventeen women, with a median age of 27 years,were submitted to autologous transplantation for relapsed (n = 21or refractory (n = 10 Hodgkin’s lymphoma. Results: Mortalityrelated to treatment in the first 100 days after transplant was 3.2%.With a mean follow-up period of 18 months (range: 1 to 88 months,the probability of global survival and progression-free survival in18 months was 84 and 80%, respectively. The probability of globalsurvival and progression-free survival at 18 months for patients withchemosensitive relapses (n = 21 was 95 and 90%, respectively,versus 60 and 45% for patients with relapses resistant to chemotherapy(n = 10 (p = 0.001 for global survival; p = 0.003 for progressionfreesurvival. In the multivariate analysis, absence of disease or pretransplant disease < 5 cm were favorable factors for global survival (p= 0.02; RR: 0.072; 95%CI: 0.01-0.85 and progression-free survival (p= 0.01; RR: 0.040; 95%CI: 0.007-0.78. Conclusion: Autologous transplantation of stem-cells is a therapeutic option for Hodgkin’s lymphoma patients after the first relapse. Promising results were observed in patients with a low tumor burden at transplant.

  8. Successful Treatment of Osgood–Schlatter Disease with Autologous-Conditioned Plasma in Two Patients

    OpenAIRE

    Danneberg, Dirk-Jonas

    2017-01-01

    Osgood–Schlatter Disease (OSD) is a painful, growth-related overuse condition of the tibial tuberosity, leading to inflammation of the patellar ligament at the tibial tuberosity. It primarily affects young adolescents, athletic population, and usually, resolves with age or skeletal maturity. Therapy is usually conservative, with surgery indicated in a minority of cases. For patients with treatment-resistant or refractory OSD, an alternative is the application of autologous platelet concentrat...

  9. Autologous Bone Marrow Transplantation in Multiple Sclerosis: Biomarker Relevance for Patient Recruitment and Follow up.

    Science.gov (United States)

    Londoño, Ana C; Mora, Carlos A

    2016-10-01

    Despite the current availability of disease modifying therapies for the treatment of multiple sclerosis, there are still patients who suffer from severe neurological dysfunction in the relapsing-remitting or early progressive forms of the disease. For these patients autologous hematopoietic stem cell transplant offers an important therapeutic solution to prevent progression to irreversible disability. In spite of multiple studies in the last two decades, patient inclusion criteria, protocols for peripheral blood stem cell mobilization and bone marrow cell conditioning and methodology of follow up for autologous hematopoietic stem cell transplant in multiple sclerosis have not been strictly unified. We reviewed five recent clinical studies that confirmed the positive outcome of transplant in spite of disclosing significant differences in methodology of enrollment including patient disease subtypes, disease duration range, disability, regimens of peripheral blood stem cell mobilization and bone marrow cell conditioning, scheduling of imaging studies after transplant, and absence of laboratory biomarkers consistently applied to these studies. Therapy with autologous hematopoietic stem cell transplant has shown best results among young individuals with severe relapsing-remitting or early progressive disease through its ability to maintain no evidence of disease activity status in a significantly higher proportion of patients after transplant in comparison to patients treated with disease modifying therapies. Important cross-sectional differences in the reviewed studies were found. A specific and careful selection of biomarkers, based on the current physiopathological mechanisms known to result in multiple sclerosis, will contribute to a better and earlier patient selection for autologous hematopoietic stem cell transplant and follow up process. An objective and measurable response could be obtained with the determination of biomarkers at the onset of treatment and

  10. Quantitative magnetic resonance imaging in autologous bone marrow transplantation for Hodgkin's disease.

    OpenAIRE

    Smith, S. R.; Williams, C. E.; Edwards, R. H.; Davies, J. M.

    1989-01-01

    Fifteen consecutive patients with refractory or relapsed Hodgkin's disease (HD) referred for autologous bone marrow transplantation (ABMT) underwent quantitative magnetic resonance (MR) studies of the lumbar vertebral bone marrow. Markedly elevated lumbar vertebral marrow T1 values suggestive of bone marrow involvement with HD were seen in four patients, two of whom had no evidence of HD on bilateral iliac crest bone marrow biopsy. Serial studies showed normalisation of T1 values in the post-...

  11. Autologous Stem Cell Transplantation in Patients with Acute Myeloid Leukemia: a Single-Centre Experience

    Directory of Open Access Journals (Sweden)

    Kakucs Enikő

    2013-04-01

    Full Text Available Introduction: Autologous haemopoietic stem cell transplantation (SCT is an important treatment modality for patients with acute myeloid leukemia with low and intermediate risk disease. It has served advantages over allogenic transplantation, because it does not need a matched donor, there is no graft versus host disease, there are less complications and a faster immune reconstitution than in the allo-setting. The disadvantage is the lack of the graft versus leukaemia effect.

  12. [Experimental study on bone defect treated by combined autologous bone marrow transplantation, cuttlebone, and sodium hyaluronate].

    Science.gov (United States)

    Yi, Hong-cheng; Tang, Liang-hua; Zhang, Xue-peng

    2011-08-01

    To study the feasibility of repairing bone defect by combined autologous bone marrow transplantation, cuttebone, and sodium hyaluronate. Forty-eight New Zealand rabbits were randomly divided into four groups. The 10-mm bone defect of the radial shaft animal model was established, with the periosteum remained. Rabbits of Group A were treated by autologous bone marrow transplantation, cuttlebone, and sodium hyaluronate. Those of Group B were treated by autologous bone marrow transplantation and cuttlebone. Rabbits of Group C were implanted with cuttlebone and sodium hyaluronate. And rabbits of Group D were taken as the blank control. There were twelve rabbits in each group. All rabbits were sacrificed, and the general histological examination, X-ray test, the pathohistological observation and scoring, the new born formation area measurement were performed at 2-week, 4-week, 8-week, and 12-week after transplantation respectively. The capacities for bone transplantation and defect repairing were compared and analyzed as well. The bone defect of Group A was completely repaired at week 12. The comprehensive indices at each time point were superior to those of the rest groups, showing statistical significance (Pbone repair in Group B and Group C were somewhat poor, with the repairing effect inferior to that of Group A. The bone repairing was better in Group B than in Group C. Most portion of the bone defect in Group D was filled with fibrous tissue and muscular tissue, with little bone repairing. The combined autologous bone marrow transplantation, cuttlebone, and sodium hyaluronate showed obviously synergistically bone forming capacities. It could be taken as a substitute material for transplantation.

  13. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    International Nuclear Information System (INIS)

    Puente, Pilar de la; Ludeña, Dolores; López, Marta; Ramos, Jennifer; Iglesias, Javier

    2013-01-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  14. Use of autologous pericardium for mitral leaflet reconstruction in a child with endocarditis

    Directory of Open Access Journals (Sweden)

    Olcay Murat Disli

    2013-06-01

    Full Text Available We present a case of successful repair of the mitral valve for active infective endocarditis. Mitral valve repair was performed through debridement of vegetation and abscess, resection and repair of the posterior mitral leaflet and posterior repair with autologous pericardium. Postoperative period was uneventfully, with no evidence of recurrent infection, and echocardiogram showed mitral valve competence with mild mitral regurgitation. We demonstrate that valve repair is a feasible choice in cases of active endocarditis in children.

  15. Funding analysis of bilateral autologous free-flap breast reconstructions in Australia.

    Science.gov (United States)

    Sinha, Shiba; Ruskin, Olivia; McCombe, David; Morrison, Wayne; Webb, Angela

    2015-08-01

    Bilateral breast reconstructions are being increasingly performed. Autologous free-flap reconstructions represent the gold standard for post-mastectomy breast reconstruction but are resource intensive. This study aims to investigate the difference between hospital reimbursement and true cost of bilateral autologous free-flap reconstructions. Retrospective analysis of patients who underwent bilateral autologous free-flap reconstructions at a single Australian tertiary referral centre was performed. Hospital reimbursement was determined from coding analysis. A true cost analysis was also performed. Comparisons were made considering the effect of timing, indication and complications of the procedure. Forty-six bilateral autologous free-flap procedures were performed (87 deep inferior epigastric perforators (DIEPs), four superficial inferior epigastric artery perforator flaps (SIEAs) and one muscle-sparing free transverse rectus abdominis myocutaneous flap (MS-TRAM)). The mean funding discrepancy between hospital reimbursement and actual cost was $12,137 ± $8539 (mean ± standard deviation (SD)) (n = 46). Twenty-four per cent (n = 11) of the cases had been coded inaccurately. If these cases were excluded from analysis, the mean funding discrepancy per case was $9168 ± $7453 (n = 35). Minor and major complications significantly increased the true cost and funding discrepancy (p = 0.02). Bilateral free-flap breast reconstructions performed in Australian public hospitals result in a funding discrepancy. Failure to be economically viable threatens the provision of this procedure in the public system. Plastic surgeons and hospital managers need to adopt measures in order to make these gold-standard procedures cost neutral. Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

  16. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Puente, Pilar de la, E-mail: pilardelapuentegarcia@gmail.com [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain); Ludeña, Dolores [Pathology Service, University Hospital of Salamanca, P/San Vicente 58-182, 37007 Salamanca (Spain); López, Marta; Ramos, Jennifer; Iglesias, Javier [Tissue Bank, San Francisco Clinic Foundation, Av./Facultad 51, 5°, 24004 León (Spain)

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  17. Use of autologous bone graft in anterior cervical decompression: morbidity & quality of life analysis.

    LENUS (Irish Health Repository)

    Heneghan, Helen M

    2009-01-01

    BACKGROUND: Autologous iliac crest graft has long been the gold standard graft material used in cervical fusion. However its harvest has significant associated morbidity, including protracted postoperative pain scores at the harvest site. Thus its continued practice warrants scrutiny, particularly now that alternatives are available. Our aims were to assess incidence and nature of complications associated with iliac crest harvest when performed in the setting of Anterior Cervical Decompression (ACD). Also, to perform a comparative analysis of patient satisfaction and quality of life scores after ACD surgeries, when performed with and without iliac graft harvest. METHODS: All patients who underwent consecutive ACD procedures, with and without the use of autologous iliac crest graft, over a 48 month period were included (n = 53). Patients were assessed clinically at a minimum of 12 months postoperatively and administered 2 validated quality of life questionnaires: the SF-36 and Cervical Spine Outcomes Questionnaires (Response rate 96%). Primary composite endpoints included incidence of bone graft donor site morbidity, pain scores, operative duration, and quality of life scores. RESULTS: Patients who underwent iliac graft harvest experienced significant peri-operative donor site specific morbidity, including a high incidence of pain at the iliac crest (90%), iliac wound infection (7%), a jejunal perforation, and longer operative duration (285 minutes vs. 238 minutes, p = 0.026). Longer term follow-up demonstrated protracted postoperative pain at the harvest site and significantly lower mental health scores on both quality of life instruments, for those patients who underwent autologous graft harvest CONCLUSION: ACD with iliac crest graft harvest is associated with significant iliac crest donor site morbidity and lower quality of life at greater than 12 months post operatively. This is now avoidable by using alternatives to autologous bone without compromising clinical

  18. Clinical application of tissue engineered human heart valves using autologous progenitor cells.

    Science.gov (United States)

    Cebotari, Serghei; Lichtenberg, Artur; Tudorache, Igor; Hilfiker, Andres; Mertsching, Heike; Leyh, Rainer; Breymann, Thomas; Kallenbach, Klaus; Maniuc, Liviu; Batrinac, Aurel; Repin, Oleg; Maliga, Oxana; Ciubotaru, Anatol; Haverich, Axel

    2006-07-04

    Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients. TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.

  19. Treatment of periodontal intrabony defects using autologous periodontal ligament stem cells: a randomized clinical trial

    OpenAIRE

    Chen, Fa-Ming; Gao, Li-Na; Tian, Bei-Min; Zhang, Xi-Yu; Zhang, Yong-Jie; Dong, Guang-Ying; Lu, Hong; Chu, Qing; Xu, Jie; Yu, Yang; Wu, Rui-Xin; Yin, Yuan; Shi, Songtao; Jin, Yan

    2016-01-01

    Background Periodontitis, which progressively destroys tooth-supporting structures, is one of the most widespread infectious diseases and the leading cause of tooth loss in adults. Evidence from preclinical trials and small-scale pilot clinical studies indicates that stem cells derived from periodontal ligament tissues are a promising therapy for the regeneration of lost/damaged periodontal tissue. This study assessed the safety and feasibility of using autologous periodontal ligament stem ce...

  20. Autologous Transplantation of Amniotic Fluid-Derived Mesenchymal Stem Cells into Sheep Fetuses.

    Science.gov (United States)

    Shaw, S W Steven; Bollini, Sveva; Nader, Khalil Abi; Gastaldello, Annalisa; Mehta, Vedanta; Filppi, Elisa; Cananzi, Mara; Gaspar, H Bobby; Qasim, Waseem; De Coppi, Paolo; David, Anna L

    2016-03-01

    Long-term engraftment and phenotype correction has been difficult to achieve in humans after in utero stem cell transplantation mainly because of allogeneic rejection. Autologous cells could be obtained during gestation from the amniotic fluid with minimal risk for the fetus and the mother. Using a sheep model, we explored the possibility of using amniotic fluid mesenchymal stem cells (AFMSCs) for autologous in utero stem cell/gene therapy. We collected amniotic fluid (AF) under ultrasound-guided amniocentesis in early gestation pregnant sheep ( n = 9, 58 days of gestation, term = 145 days). AFMSCs were isolated and expanded in all sampled fetal sheep. Those cells were transduced using an HIV vector encoding enhanced green fluorescent protein (GFP) with 63.2% (range 38.3-96.2%) transduction efficiency rate. After expansion, transduced AFMSCs were injected into the peritoneal cavity of each donor fetal sheep at 76 days under ultrasound guidance. One ewe miscarried twin fetuses after amniocentesis. Intraperitoneal injection was successful in the remaining 7 fetal sheep giving a 78% survival for the full procedure. Tissues were sampled at postmortem examination 2 weeks later. PCR analysis detected GFP-positive cells in fetal tissues including liver, heart, placenta, membrane, umbilical cord, adrenal gland, and muscle. GFP protein was detected in these tissues by Western blotting and further confirmed by cytofluorimetric and immunofluorescence analyses. This is the first demonstration of autologous stem cell transplantation in the fetus using AFMSCs. Autologous cells derived from AF showed widespread organ migration and could offer an alternative way to ameliorate prenatal congenital disease.

  1. Arthroscopic osteochondral autologous transplantation for the treatment of osteochondritis dissecans of the femoral head

    Directory of Open Access Journals (Sweden)

    Uchida Soshi

    2017-01-01

    Full Text Available Osteochondritis dissecans (OCD of the femoral head is an unusual cause of hip pain. It can be associated with other intra-articular pathologies including: acetabular labral tears or bone deformities such as Legg-Calve-Perthes Disease (LCPD. In this article, we propose a modern surgical technique using an arthroscopic antegrade and retrograde osteochondral autologous transplantation (OAT procedure for assessing and treating OCD lesions of the femoral head.

  2. Microbial metabolite butyrate facilitates M2 macrophage polarization and function.

    Science.gov (United States)

    Ji, Jian; Shu, Dingming; Zheng, Mingzhu; Wang, Jie; Luo, Chenglong; Wang, Yan; Guo, Fuyou; Zou, Xian; Lv, Xiaohui; Li, Ying; Liu, Tianfei; Qu, Hao

    2016-04-20

    Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo. The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization, and delineated new insights into the immune interplay underlying inflammatory bowel disease.

  3. Macrophages and vascular adhesion molecules in oral Kaposi's sarcoma.

    Science.gov (United States)

    MacPhail, L A; Dekker, N P; Regezi, J A

    1996-10-01

    Kaposi's sarcoma (KS) is a heterogeneous tumor where spindle cells are predominant and macrophages and factor XIIIa positive dendrocytes are abundant. The origin of the macrophages and dendrocytes is unclear, although their numbers suggest a critical role in KS pathogenesis. To determine if KS macrophages are recruited from the blood stream or proliferate on-site, we examined biopsy specimens 1) for expression and distribution of vascular adhesion molecules (PECAM-1, ELAM-1, ICAM-1, VCAM-1, P-selectin, L-selectin) and the macrophage-associated adhesion-molecule ligand, VLA-4; 2) for dual expression of proliferation (Ki-67) and lineage-associated markers (KP-1, CD34, factor XIIIa, LCA); and 3) for dual expression of macrophage (KP-1) and endothelial cell (CD34) associated markers. Avidinbiotin peroxidase techniques were used. Resident vessels were found to strongly express PECAM-1, ELAM-1, ICAM-1, P-selectin, and moderately express VCAM-1 and VLA-4. Tumor spindle cells showed less intense expression of ELAM-1, ICAM-1 and P-selectin. The most frequent double-stain combination was Ki-67 + CD34+. In contrast, the combinations of Ki-67 + KP-1+, Ki-67 + XIIIa+ and Ki-67 + LCA+ were rarely seen. The enhanced expression of adhesion molecules on resident vessels and the lack of evidence of macrophage proliferation suggest that the abundant macrophages in KS are recruited from the blood stream.

  4. Impact of in vitro gallium arsenide exposure on macrophages

    International Nuclear Information System (INIS)

    Harrison, M.Travis; Hartmann, Constance B.; McCoy, Kathleen L.

    2003-01-01

    The semiconductor gallium arsenide (GaAs) is classified as an immunotoxicant and a carcinogen. We previously showed that GaAs in vivo induces several phenotypic changes in macrophages located at the exposure site, indicative of an activated state. These physiological alterations may be a primary or secondary consequence of chemical exposure. To discern primary influences, our current study examined the in vitro effects of the chemical on macrophage cell lines and murine peritoneal macrophages. GaAs augmented cathepsins L and B proteolytic activities in all three sources of macrophages. Expression of the two mature isoforms of invariant chain and its cleavage fragment was also significantly increased, indicating that the chemical directly affects macrophages. However, GaAs did not alter the overall cell surface expression of major histocompatibility complex class II molecules on macrophages nor influence their ability to stimulate antigen-specific helper T cell hybridomas to respond to intact antigens that require processing. These findings raise the possibility that the chemical's complete in vivo impact may involve cytokines. Further, GaAs in vitro enhanced steady-state cathepsin L protein, and cathepsins L and B mRNA expression in macrophages, indicating that GaAs may alter gene expression, which may contribute to the chemical's adverse biological effects

  5. Macrophage polarization in response to ECM coated polypropylene mesh.

    Science.gov (United States)

    Wolf, Matthew T; Dearth, Christopher L; Ranallo, Christian A; LoPresti, Samuel T; Carey, Lisa E; Daly, Kerry A; Brown, Bryan N; Badylak, Stephen F

    2014-08-01

    The host response to implanted biomaterials is a highly regulated process that influences device functionality and clinical outcome. Non-degradable biomaterials, such as knitted polypropylene mesh, frequently elicit a chronic foreign body reaction with resultant fibrosis. Previous studies have shown that an extracellular matrix (ECM) hydrogel coating of polypropylene mesh reduces the intensity of the foreign body reaction, though the mode of action is unknown. Macrophage participation plays a key role in the development of the foreign body reaction to biomaterials, and therefore the present study investigated macrophage polarization following mesh implantation. Spatiotemporal analysis of macrophage polarization was conducted in response to uncoated polypropylene mesh and mesh coated with hydrated and dry forms of ECM hydrogels derived from either dermis or urinary bladder. Pro-inflammatory M1 macrophages (CD86+/CD68+), alternatively activated M2 macrophages (CD206+/CD68+), and foreign body giant cells were quantified between 3 and 35 days. Uncoated polypropylene mesh elicited a dominant M1 response at the mesh fiber surface, which was decreased by each ECM coating type beginning at 7 days. The diminished M1 response was accompanied by a reduction in the number of foreign body giant cells at 14 and 35 days, though there was a minimal effect upon the number of M2 macrophages at any time. These results show that ECM coatings attenuate the M1 macrophage response and increase the M2/M1 ratio to polypropylene mesh in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Impact of in vitro gallium arsenide exposure on macrophages.

    Science.gov (United States)

    Harrison, M Travis; Hartmann, Constance B; McCoy, Kathleen L

    2003-01-01

    The semiconductor gallium arsenide (GaAs) is classified as an immunotoxicant and a carcinogen. We previously showed that GaAs in vivo induces several phenotypic changes in macrophages located at the exposure site, indicative of an activated state. These physiological alterations may be a primary or secondary consequence of chemical exposure. To discern primary influences, our current study examined the in vitro effects of the chemical on macrophage cell lines and murine peritoneal macrophages. GaAs augmented cathepsins L and B proteolytic activities in all three sources of macrophages. Expression of the two mature isoforms of invariant chain and its cleavage fragment was also significantly increased, indicating that the chemical directly affects macrophages. However, GaAs did not alter the overall cell surface expression of major histocompatibility complex class II molecules on macrophages nor influence their ability to stimulate antigen-specific helper T cell hybridomas to respond to intact antigens that require processing. These findings raise the possibility that the chemical's complete in vivo impact may involve cytokines. Further, GaAs in vitro enhanced steady-state cathepsin L protein, and cathepsins L and B mRNA expression in macrophages, indicating that GaAs may alter gene expression, which may contribute to the chemical's adverse biological effects. Copyright 2003 Elsevier Science (USA)

  7. Unique proteomic signatures distinguish macrophages and dendritic cells.

    Directory of Open Access Journals (Sweden)

    Lev Becker

    Full Text Available Monocytes differentiate into heterogeneous populations of tissue macrophages and dendritic cells (DCs that regulate inflammation and immunity. Identifying specific populations of myeloid cells in vivo is problematic, however, because only a limited number of proteins have been used to assign cellular phenotype. Using mass spectrometry and bone marrow-derived cells, we provided a global view of the proteomes of M-CSF-derived macrophages, classically and alternatively activated macrophages, and GM-CSF-derived DCs. Remarkably, the expression levels of half the plasma membrane proteins differed significantly in the various populations of cells derived in vitro. Moreover, the membrane proteomes of macrophages and DCs were more distinct than those of classically and alternatively activated macrophages. Hierarchical cluster and dual statistical analyses demonstrated that each cell type exhibited a robust proteomic signature that was unique. To interrogate the phenotype of myeloid cells in vivo, we subjected elicited peritoneal macrophages harvested from wild-type and GM-CSF-deficient mice to mass spectrometric and functional analysis. Unexpectedly, we found that peritoneal macrophages exhibited many features of the DCs generated in vitro. These findings demonstrate that global analysis of the membrane proteome can help define immune cell phenotypes in vivo.

  8. Monocytic MDSCs regulate macrophage-mediated xenogenic cytotoxicity.

    Science.gov (United States)

    Maeda, Akira; Eguchi, Hiroshi; Nakahata, Kengo; Lo, Pei-Chi; Yamanaka, Kazuaki; Kawamura, Takuji; Matsuura, Rei; Sakai, Rieko; Asada, Mayumi; Okuyama, Hiroomi; Miyagawa, Shuji

    2015-10-01

    Xenotransplantation is considered to be one of the most attractive strategies for overcoming the worldwide shortage of organs. However, many obstructions need to be overcome before it will achieve clinical use in patients. One such obstacle is the development of an effective immunosuppressive strategy. We previously reported that myeloid-derived suppressor cells (MDSCs), a heterogeneous population of progenitor and immature myeloid cells, suppress xenogenic CTL-mediated cytotoxicity. Because of their heterogeneous nature, MDSC can function via several suppressive mechanisms that disrupt both innate and adaptive immunity. Since macrophages play a pivotal role in the rejection of a xenograft, in this study, we evaluated the suppressive effects of MDSC against macrophage-mediated xenogenic rejection. To evaluate the effect of monocyte-derived MDSCs on xenogenic immune reactions, a CFSE(carboxyfluorescein diacetate, succinimidyl ester)assay was employed to assess cytotoxicity. While, in the absence of activation, primed MDSCs had no detectable effect on macrophage-induced cytotoxicity against SEC cells, LPS-activated MDSCs were found to significantly suppress xenogenic cytotoxicity. A CFSE cytotoxicity assay revealed that MDSCs significantly suppressed macrophage-induced cytotoxicity. Furthermore, an indoleamine 2,3 dioxygenase (IDO) inhibitor, 1-methyl tryptophan (1-MT), abolished the MDSC-induced suppression of macrophage-mediated xeno-rejection, indicating that MDSCs may suppress macrophage-mediated cytotoxicity in an IDO-dependent manner. These findings indicate that MDSCs have great potential for immunosuppressing macrophage-mediated xeno-rejection. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Multiple Myeloma Macrophages: Pivotal Players in the Tumor Microenvironment

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    Simona Berardi

    2013-01-01

    Full Text Available Tumor microenvironment is essential for multiple myeloma (MM growth, progression, and drug resistance through provision of survival signals and secretion of growth and proangiogenic factors. This paper examines the importance of macrophages within MM bone marrow (BM microenvironment, referred to as MM-associated macrophages, as a potential niche component that supports tumor plasma cells. These macrophages are derived from peripheral blood monocytes recruited into the tumor. Upon activation by MM plasma cells and mesenchymal stromal cells, macrophages can release growth factors, proteolytic enzymes, cytokines, and inflammatory mediators that promote plasma cell growth and survival. Macrophages promote tumor progression through several mechanisms including angiogenesis, growth, and drug resistance. Indeed, these macrophages are essential for the induction of an angiogenic response through vasculogenic mimicry, and this ability proceeds in step with progression of the plasma cell tumors. Data suggest that macrophages play an important role in the biology and survival of patients with MM, and they may be a target for the MM antivascular management.

  10. Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC: first clinical experience and evidence of an immune response

    Directory of Open Access Journals (Sweden)

    Schendel Dolores J

    2007-09-01

    Full Text Available Abstract Background Given the considerable toxicity and modest benefit of adjuvant chemotherapy for non-small cell lung cancer (NSCLC, there is clearly a need for new treatment modalities in the adjuvant setting. Active specific immunotherapy may represent such an option. However, clinical responses have been rare so far. Manipulating the host by inducing lymphopenia before vaccination resulted in a magnification of the immune response in the preclinical setting. To evaluate feasibility and safety of an irradiated, autologous tumor cell vaccine given following induction of lymphopenia by chemotherapy and reinfusion of autologous peripheral blood mononuclear cells (PBMC, we are currently conducting a pilot-phase I clinical trial in patients with NSCLC following surgical resection. This paper reports on the first clinical experience and evidence of an immune response in patients suffering from NSCLC. Methods NSCLC patients stages I-IIIA are recruited. Vaccines are generated from their resected lung specimens. Patients undergo leukapheresis to harvest their PBMC prior to or following the surgical procedure. Furthermore, patients receive preparative chemotherapy (cyclophosphamide 350 mg/m2 and fludarabine 20 mg/m2 on 3 consecutive days for induction of lymphopenia followed by reconstitution with their autologous PBMC. Vaccines are administered intradermally on day 1 following reconstitution and every two weeks for a total of up to five vaccinations. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF is given continuously (at a rate of 50 μg/24 h at the site of vaccination via minipump for six consecutive days after each vaccination. Results To date, vaccines were successfully manufactured for 4 of 4 patients. The most common toxicities were local injection-site reactions and mild constitutional symptoms. Immune responses to chemotherapy, reconstitution and vaccination are measured by vaccine site and delayed type hypersensitivity (DTH skin

  11. Autologous Bone Marrow-Derived Stem Cells in Spinal Cord Injury.

    Science.gov (United States)

    Bansal, Himanshu; Verma, Poonam; Agrawal, Anupama; Leon, Jerry; Sundell, I Birgitta; Koka, Prasad S

    Spinal cord injury is a traumatic neurological condition which makes the patient disable. Its management still remains challenging but advancements in the regenerative medicine have changed the approach of treating this serious debilitating condition of the central nervous system. Cell based therapies can restore function in spinal cord injury by replacing the lost neural tissue. These therapies also rejuvenate the existing intact neurons by facilitating remyelination and by repairing and reducing progressive tissue damage and scarring. Autologous bone marrow stem cells were collected from the patients. 5 ml of the processed sample was injected back into the patients via lumbar puncture at L1/L2 level. The bone marrow harvesting and administration was repeated every 4 weeks 3 times (12 weeks). Significant improvements were noticed following the injections into the patients with the duration of injury less than 6 months. ASIA grade improvements were observed in 6 out of 10 patients. VTC and walking, at least with the support, was restored in eight patients. Bladder control and sexual functions improved in three and five patients respectively. Eight patients exhibited decreased spasticity. We believe that autologous bone marrow stem cells contributed towards the neuroplaticity and/or paracrine effect due to which we observed the considerable improvements in the conditions of the patients. This preliminary proof of patient improvement reinforces the potential of autologous bone marrow stem cell treatment in the patients suffering from Spinal Cord Injury. Although the results are encouraging further studies are needed to substantiate the claims.

  12. Intrasphincteric autologous myoblast injections with electrical stimulation for stress urinary incontinence.

    Science.gov (United States)

    Blaganje, Mija; Lukanović, Adolf

    2012-05-01

    To assess the feasibility and safety of ultrasound-guided autologous myoblast injections into the external urethral sphincter followed by electrical stimulation (ES) as a possible 2-step treatment for stress urinary incontinence (SUI). Autologous myoblasts isolated from a biceps muscle sample were injected under transurethral ultrasound guidance into the external urethral sphincter of 38 female patients. The patients also underwent ES postoperatively to enhance cell integration. Treatment feasibility, as well as possible intraoperative and postoperative complications, was assessed 6weeks after the injections. Additionally, the effects of the myoblast injections followed by an ES cycle were compared to those of a preoperative ES cycle undergone by the same patients. No serious adverse events or complications were noted and the procedure was well tolerated. Compared with the objective and subjective measurements collected after the preoperative ES cycle, the corresponding measurements obtained 6weeks postoperatively, after the completion of a second ES cycle, indicated considerable improvement. The results to the stress test were negative for 29 (78.4%) of the patients, 5 (13.5%) considered their SUI cured, and 29 (78.4%) reported improvement. Intrasphincteric autologous myoblast injections followed by ES is minimally invasive and feasible, and safely produced promising initial results. EU Clinical Trials EudraCT No. 2009-012389-30 ClinicalTrials.gov identifier: NCT01355133. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  13. A successful case of a para-aortic lymphocele treated with autologous peripheral blood injection

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    Keiji Nishibeppu, MD

    2017-12-01

    Full Text Available A lymphocele is one of the complications of systematic pelvic or para-aortic lymphadenectomy. Although most patients are entirely asymptomatic, our patient exhibited an obstructive ileus at the jejunum compressed by a lymphocele. We report here a case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection. A 68-year-old woman with sigmoid colon cancer (T3N2bM1a underwent laparoscopic sigmoidectomy. After 4 courses of chemotherapy (CapeOX + Bmab, para-aortic lymphadenectomy was additionally performed. One month later, an obstructive ileus occurred suddenly due to a lymphocele. A drainage catheter was placed into the lymphocele and a total of 35 mL of autologous peripheral blood was injected in 4 divided doses through the catheter. The volume of the lymphocele gradually reduced and the ileus improved after blood injection. This is the first report of a successful case of a subsequent para-aortic lymphocele treated with autologous peripheral blood injection without any complications.

  14. Medialization Thyroplasty Using Autologous Nasal Septal Cartilage for Treating Unilateral Vocal Fold Paralysis

    Science.gov (United States)

    Khalil, Yasser A.; Malki, Khalid H.; Farahat, Mohamad

    2011-01-01

    Objectives A persistent insufficiency of glottal closure is mostly a consequence of impaired unilateral vocal fold movement. Functional surgical treatment is required because of the consequential voice, breathing and swallowing impairments. The goal of the study was to determine the functional voice outcomes after medialization thyroplasty with using autologous septal cartilage from the nose. Methods External vocal fold medialization using autologous nasal septal cartilage was performed on 15 patients (6 females and 9 males; age range, 30 to 57 years). Detailed functional examinations were performed for all the patients before and after the surgery and this included perceptual voice assessment, laryngostroboscopic examination and acoustic voice analysis. Results All the patients reported improvement of voice quality post-operatively. Laryngostroboscopy revealed almost complete glottal closure after surgery in the majority of patients. Acoustic and perceptual voice assessment showed significant improvement post-operatively. Conclusion Medialization thyroplasty using an autologous nasal septal cartilage implant offers good tissue tolerability and significant improvement of the subjective and objective functional voice outcomes. PMID:21949581

  15. Comparison of Complications Following Cranioplasty Using a Sterilized Autologous Bone Flap or Polymethyl Methacrylate.

    Science.gov (United States)

    Kim, Sung Hoon; Kang, Dong Soo; Cheong, Jin Hwan; Kim, Jung Hee; Song, Kwan Young; Kong, Min Ho

    2017-04-01

    The aims of current study are to compare complications following cranioplasty (CP) using either sterilized autologous bone or polymethyl methacrylate (PMMA), and to identify the risk factors for two of the most common complications: bone flap resorption (BFR) and surgical site infection (SSI). Between January 2004 and December 2013, 127 patients underwent CP and were followed at least 12 months. Variables, including sex, age, initial diagnosis, time interval between decompressive craniectomy (DC) and CP, operation time, size of bone flap, and presence of ventriculo-peritoneal shunt, were analyzed to identify the risk factors for BFR and SSI. A total of 97 (76.4%) patients underwent CP using PMMA (Group I) and 30 (23.6%) underwent CP using autologous bone (Group II). SSI occurred in 8 (8.2%) patients in Group I, and in 2 (6.7%) in Group II; there was no statistically significant difference between the groups ( p =1.00). No statistically significant risk factors for SSI were found in either group. In Group I, there was no reported case of BFR. In Group II patients, BFR developed in 18 (60.0%) patients at the time of CP (Type 1 BFR), and at 12-month follow up (Type 2 BFR) in 4 (13.3%) patients. No statistically significant risk factors for BFR were found in Group II. CP using sterilized autologous bone result in a significant rate of BFR. PMMA, however, is a safe alloplastic material for CP, as it has low complication rate.

  16. Autologous serum and plasma skin tests in chronic spontaneous urticaria: A reappraisal

    Directory of Open Access Journals (Sweden)

    Muthu Sendhil Kumaran

    2017-01-01

    Full Text Available Aim: The objective of this study was to assess autologous serum skin test (ASST vs autologous plasma skin test (APST response in chronic spontaneous urticaria (CSU patients and study the significance of intensity of positive responses in relation to clinicoepidemiological parameters. Materials and Methods: One hundred CSU patients and 100 age and sex-matched controls were recruited. The demographic and clinical features were recorded in all patients and routine investigations were performed. ASST and APST tests were performed as per the standard guidelines. Results: The mean duration of illness was 4.85 ± 5.07 years, 90% patients were APST (+, 68% ASST (+, and 22 patients were only APST (+. Positive predictive value (PPV of ASST and APST was 90.7% and 95.7%, respectively. A significant inverse association was seen between thyroid status and serum IgE levels with APST and ASST positivity. Conclusion: APST appears to have better PPV and high intensity of positive response on autologous tests, and correlates with ANA positivity and angioedema.

  17. Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells.

    Science.gov (United States)

    Lee, Andrew S; Xu, Dan; Plews, Jordan R; Nguyen, Patricia K; Nag, Divya; Lyons, Jennifer K; Han, Leng; Hu, Shijun; Lan, Feng; Liu, Junwei; Huang, Mei; Narsinh, Kazim H; Long, Charles T; de Almeida, Patricia E; Levi, Benjamin; Kooreman, Nigel; Bangs, Charles; Pacharinsak, Cholawat; Ikeno, Fumiaki; Yeung, Alan C; Gambhir, Sanjiv S; Robbins, Robert C; Longaker, Michael T; Wu, Joseph C

    2011-09-16

    Derivation of patient-specific induced pluripotent stem cells (iPSCs) opens a new avenue for future applications of regenerative medicine. However, before iPSCs can be used in a clinical setting, it is critical to validate their in vivo fate following autologous transplantation. Thus far, preclinical studies have been limited to small animals and have yet to be conducted in large animals that are physiologically more similar to humans. In this study, we report the first autologous transplantation of iPSCs in a large animal model through the generation of canine iPSCs (ciPSCs) from the canine adipose stromal cells and canine fibroblasts of adult mongrel dogs. We confirmed pluripotency of ciPSCs using the following techniques: (i) immunostaining and quantitative PCR for the presence of pluripotent and germ layer-specific markers in differentiated ciPSCs; (ii) microarray analysis that demonstrates similar gene expression profiles between ciPSCs and canine embryonic stem cells; (iii) teratoma formation assays; and (iv) karyotyping for genomic stability. Fate of ciPSCs autologously transplanted to the canine heart was tracked in vivo using clinical positron emission tomography, computed tomography, and magnetic resonance imaging. To demonstrate clinical potential of ciPSCs to treat models of injury, we generated endothelial cells (ciPSC-ECs) and used these cells to treat immunodeficient murine models of myocardial infarction and hindlimb ischemia.

  18. Bone marrow concentrate for autologous transplantation in minipigs. Characterization and osteogenic potential of mesenchymal stem cells.

    Science.gov (United States)

    Herten, M; Grassmann, J P; Sager, M; Benga, L; Fischer, J C; Jäger, M; Betsch, M; Wild, M; Hakimi, M; Jungbluth, P

    2013-01-01

    Autologous bone marrow plays an increasing role in the treatment of bone, cartilage and tendon healing disorders. Cell-based therapies display promising results in the support of local regeneration, especially therapies using intra-operative one-step treatments with autologous progenitor cells. In the present study, bone marrow-derived cells were concentrated in a point-of-care device and investigated for their mesenchymal stem cell (MSC) characteristics and their osteogenic potential. Bone marrow was harvested from the iliac crest of 16 minipigs. The mononucleated cells (MNC) were concentrated by gradient density centrifugation, cultivated, characterized by flow cytometry and stimulated into osteoblasts, adipocytes, and chondrocytes. Cell differentiation was investigated by histological and immunohistological staining of relevant lineage markers. The proliferation capacity was determined via colony forming units of fibroblast and of osteogenic alkaline-phosphatase-positive-cells. The MNC could be enriched 3.5-fold in nucleated cell concentrate in comparison to bone marrow. Flow cytometry analysis revealed a positive signal for the MSC markers. Cells could be differentiated into the three lines confirming the MSC character. The cellular osteogenic potential correlated significantly with the percentage of newly formed bone in vivo in a porcine metaphyseal long-bone defect model. This study demonstrates that bone marrow concentrate from minipigs display cells with MSC character and their osteogenic differentiation potential can be used for osseous defect repair in autologous transplantations.

  19. [Long-term results of intracoronary transplantation of autologous bone marrow cells in dilated cardiomyopathy].

    Science.gov (United States)

    Bartolucci, Jorge; Verdugo, Fernando J; Carrion, Flavio; Abarzúa, Ema; Goset, Carlos; Lamich, Rubén; Sanhueza, Patricio; Pedreros, Pablo; Nazzal, Carolina; Khoury, Maroun; Figueroa, Fernando E

    2015-04-01

    Intracoronary delivery of autologous bone marrow mononuclear cells is an interesting therapeutic promise for patients with heart failure of different etiologies. To evaluate the long-term safety and efficacy of this therapy in patients with dilated cardiomyopathy of different etiologies under optimal medical treatment. Prospective, open-label, controlled clinical trial. Of 23 consecutive patients, 12 were assigned to autologous bone marrow mononuclear cell intracoronary transplantation, receiving a mean dose of 8.19 ± 4.43 x 10(6) CD34+ cells. Mortality, cardiovascular readmissions and cancer incidence rate, changes in functional capacity, quality of life questionnaires and echocardiographic measures from baseline, were assessed at long-term follow-up (37.7 ± 9.7 months) in patients receiving or not the cells. No significant differences were observed in mortality, cardiovascular readmissions or cancer incidence rate amongst groups. An improvement in functional class and quality of life questionnaires in the transplanted group was observed (p transplantation of autologous bone marrow mononuclear cells is feasible and safe in patients with dilated cardiomyopathy of diverse etiologies. This therapy was associated to persistent improvements in functional class and quality of life. There was also a non-significant long-term improvement of left ventricular function.

  20. Second-degree burns with six etiologies treated with autologous noncultured cell-spray grafting.

    Science.gov (United States)

    Esteban-Vives, Roger; Choi, Myung S; Young, Matthew T; Over, Patrick; Ziembicki, Jenny; Corcos, Alain; Gerlach, Jörg C

    2016-11-01

    Partial and deep partial-thickness burn wounds present a difficult diagnosis and prognosis that makes the planning for a conservative treatment versus mesh grafting problematic. A non-invasive treatment strategy avoiding mesh grafting is often chosen by practitioners based on their clinical and empirical evidence. However, a delayed re-epithelialization after conservative treatment may extend the patient's hospitalization period, increase the risk of infection, and lead to poor functional and aesthetic outcome. Early spray grafting, using non-cultured autologous cells, is under discussion for partial and deep partial-thickness wounds to accelerate the re-epithelialization process, reducing the healing time in the hospital, and minimizing complications. To address planning for future clinical studies on this technology, suitable indications will be interesting. We present case information on severe second-degree injuries after gas, chemical, electrical, gasoline, hot water, and tar scalding burns showing one patient per indication. The treatment results with autologous non-cultured cells, support rapid, uncomplicated re-epithelialization with aesthetically and functionally satisfying outcomes. Hospital stays averaged 7.6±1.6 days. Early autologous cell-spray grafting does not preclude or prevent simultaneous or subsequent traditional mesh autografting when indicated on defined areas of full-thickness injury. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

  1. Preliminary results with non-centrifuged autologous fat graft and percutaneous aponeurotomy for treating Dupuytren's disease.

    Science.gov (United States)

    Tuncel, U; Kurt, A; Gumus, M; Aydogdu, O; Güzel, N; Demir, O

    2017-10-01

    The aim of this study was to describe our experience with treating Dupuytren's disease using needle aponeurotomy and non-centrifuged autologous fat grafting. The study included 17 patients (18 hands). Patients were treated with needle aponeurotomy and non-centrifuged autologous fat graft under general anesthesia. The fat grafts were injected into the surgical area so as to stay in contact with the operated site. An extension splint was used for 1 week postoperatively and the patients received hand therapy for 3 weeks. Before the treatment, the contracture in the proximal interphalangeal and metacarpophalangeal joints was a mean of 45.06 ± 13.44 degrees and 36.56 ± 13.09 degrees, respectively. It was 1.61 ± 1.65 and -0.56 ± 3.78 degrees at 3 months, respectively. The difference between these measurements was statistically significant. The mean follow-up period was 12 months. The results were satisfactory and no complications were observed during the follow-up period. Based on the results of the study, percutaneous aponeurotomy with non-centrifuged autologous fat grafting was found to have significantly beneficial effects in the treatment of Dupuytren's disease. Copyright © 2017 SFCM. Published by Elsevier Masson SAS. All rights reserved.

  2. Establishment of autologous embryonic stem cells derived from preantral follicle culture and oocyte parthenogenesis.

    Science.gov (United States)

    Lee, Seung Tae; Choi, Mun Hwan; Lee, Eun Ju; Gong, Seung Pyo; Jang, Mi; Park, Sang Hyun; Jee, Hyang; Kim, Dae Yong; Han, Jae Yong; Lim, Jeong Mook

    2008-11-01

    To evaluate whether autologous embryonic stem cells can be established without generating clone embryos. Prospective model study. Gamete and stem cell biotechnology laboratory in Seoul National University, Seoul, Korea. F1 hybrid B6D2F1 mice. Preantral follicles were cultured, and oocytes matured in the follicles were parthenogenetically activated. Preimplantation development and stem cell characterization. More intrafollicular oocytes that were retrieved from secondary follicles matured and developed into blastocysts after parthenogenesis than those that were retrieved from primary follicles. Of those 35 blastocysts derived from 193 parthenotes, one line of colony-forming cells was established from the culturing of early secondary follicles. The established cells were positive for embryonic stem cell-specific markers and had normal diploid karyotype and telomerase activity. They differentiated into embryoid bodies in vitro and teratomas in vivo. Inducible differentiation of the established cells into neuronal lineage cells also was possible. Autologous embryonic stem cells can be established by preantral follicle culture and oocyte parthenogenesis. A combined technique of follicle culture and oocyte parthenogenesis that does not use developmentally competent oocytes has the potential to replace somatic cell nuclear transfer for autologous cell therapy.

  3. Evolution of Autologous Chondrocyte Repair and Comparison to Other Cartilage Repair Techniques

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    Ashvin K. Dewan

    2014-01-01

    Full Text Available Articular cartilage defects have been addressed using microfracture, abrasion chondroplasty, or osteochondral grafting, but these strategies do not generate tissue that adequately recapitulates native cartilage. During the past 25 years, promising new strategies using assorted scaffolds and cell sources to induce chondrocyte expansion have emerged. We reviewed the evolution of autologous chondrocyte implantation and compared it to other cartilage repair techniques. Methods. We searched PubMed from 1949 to 2014 for the keywords “autologous chondrocyte implantation” (ACI and “cartilage repair” in clinical trials, meta-analyses, and review articles. We analyzed these articles, their bibliographies, our experience, and cartilage regeneration textbooks. Results. Microfracture, abrasion chondroplasty, osteochondral grafting, ACI, and autologous matrix-induced chondrogenesis are distinguishable by cell source (including chondrocytes and stem cells and associated scaffolds (natural or synthetic, hydrogels or membranes. ACI seems to be as good as, if not better than, microfracture for repairing large chondral defects in a young patient’s knee as evaluated by multiple clinical indices and the quality of regenerated tissue. Conclusion. Although there is not enough evidence to determine the best repair technique, ACI is the most established cell-based treatment for full-thickness chondral defects in young patients.

  4. Alveolar ridge preservation with autologous particulated dentin-a case series.

    Science.gov (United States)

    Valdec, Silvio; Pasic, Pavla; Soltermann, Alex; Thoma, Daniel; Stadlinger, Bernd; Rücker, Martin

    2017-12-01

    Ridge preservation can be performed with autologous bone, alloplastic bone substitute material or a combination of both. Dentin is similar to bone in its chemical composition. In its use as bone substitute material, it undergoes a remodelling process and transforms to bone. The presented case report introduces a technique in which the extraction socket is augmented with autologous, particulated dentin. The fractured, non-savable mesial incisor of the upper jaw was carefully extracted in axial direction. After the extraction, the tooth was cleared from remaining periodontal tissue. The vital pulp tissue or a root canal filling, enamel and cementum were also removed. Following the particulation of the remaining dentin in a bone mill, the dentin particles were immediately filled orthotope into the alveolar socket. The soft tissue closure was performed with a free gingival graft of the palate. After an observation period of 4 months, an implant was placed in the augmented area, which osseointegrated successfully and could be restored prosthodontically in the following. The results of this method showed a functional and aesthetic success. The pre-implantological, autologous ridge preservation with dentin could be performed successfully. For the establishment of dentin as augmentation material for jaw augmentation procedures, a prospective, clinical trial is now necessary.

  5. Esterified hyaluronic acid and autologous bone in the surgical correction of the infra-bone defects.

    Science.gov (United States)

    Ballini, Andrea; Cantore, Stefania; Capodiferro, Saverio; Grassi, Felice Roberto

    2009-01-01

    We study the osteoinductive effect of the hyaluronic acid (HA) by using an esterified low-molecular HA preparation (EHA) as a coadjuvant in the grafting processes to produce bone-like tissue in the presence of employing autologous bone obtained from intra-oral sites, to treat infra-bone defects without covering membrane. We report on 9 patients with periodontal defects treated by EHA and autologous grafting (4 males and 5 females, all non smokers, with a mean age of 43.8 years for females, 40.0 years for males and 42 years for all the group, in good health) with a mean depth of 8.3 mm of the infra-bone defects, as revealed by intra-operative probes. Data were obtained at baseline before treatment and after 10 days, and subsequently at 6, 9, and 24 months after treatment. Clinical results showed a mean gain hi clinical attachment (gCAL) of 2.6mm of the treated sites, confirmed by radiographic evaluation. Such results suggest that autologous bone combined with EHA seems to have good capabilities in accelerating new bone formation in the infra-bone defects.

  6. [Treatment of focal bone defect in postoperative nonunion with autologous red bone marrow injection].

    Science.gov (United States)

    Tang, Zhao-hui; Zhu, Li-xing; Xu, Tu-bing; Wang, Kai; Zhou, Xin-min; Li, Qiang

    2009-07-01

    To observe the clinical effect of autologous red bone marrow injection in treating focal bone defect in postoperative nonunion. Thirteen patients with focal bone defect in postoperative nonunion (7 cases in tibia, 2 cases in femur, 4 cases in humerus), including 8 males and 5 females with the mean age of 32.5-years-old (ranging from 15 to 60 years). The bone defects were treated with autologous red bone marrow injection (1 time per 2 weeks, 5 times in total) and the X-rays of AP and LP were observed. Thirteen patients were followed up from 6 to 12 months with an average of 7.5 months. According to results of X-ray pictures, 13 cases obtained bone defect recovered completely, and the average time of union was 4 months. Autologous red bone marrow injection has ascendancy such as less wound and clear clinical effect, which can accelerate bone healing and promotes functional recovery of limb. It is a good method to treat focal bone defect in postoperative nonunion.

  7. Autologous conjunctiva transplantation with stem cells on edge of cornea for recurrent pterygium

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    Yun Wang

    2013-10-01

    Full Text Available AIM: To observe the clinical effectiveness and practicality the autologous conjunctiva transplantation with stem cells on edge of cornea for recurrent pterygium.METHODS: Of the 53 recurrent pterygium patients(57 eyes, after all pathological tissues were removed, underwent the autologous conjunctiva transplantation with stem cells on edge of cornea which were locked above conjunctival transplantation of the operated eye.RESULTS: Postopretive follow-up was 1-12 months for all 57 eyes, of which 3 eyes(5%relapsed. The corneoscleral autolysis was occurred in one eye and surgery treatment was conducted. Corneal wounds were healing and transplantations survived well for the remaining 53 patients without obvious surgical marks. Cure rate was 93%.CONCLUSION: Autologous conjunctiva transplantation with stem cells on edge of cornea for recurrent pterygium can meet the aesthetic requirements of the some patients, with the advantages of obtaining material easily, faster wound healing, lower postoperative recurrence rate, meeting the aesthetic needs of some patients and improving postoperative results. Thus, it is an ideal surgery and is worthy of applying on primary hospital.

  8. An overview on autologous fibrin glue in bone tissue engineering of maxillofacial surgery

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    Azizollah Khodakaram-Tafti

    2017-01-01

    Full Text Available The purpose of this review is to have an overview on the applications on the autologous fibrin glue as a bone graft substitute in maxillofacial injuries and defects. A search was conducted using the databases such as Medline or PubMed and Google Scholar for articles from 1985 to 2016. The criteria were “Autograft,” “Fibrin tissue adhesive,” “Tissue engineering,” “Maxillofacial injury,” and “Regenerative medicine.” Bone tissue engineering is a new promising approach for bone defect reconstruction. In this technique, cells are combined with three-dimensional scaffolds to provide a tissue-like structure to replace lost parts of the tissue. Fibrin as a natural scaffold, because of its biocompatibility and biodegradability, and the initial stability of the grafted stem cells is introduced as an excellent scaffold for tissue engineering. It promotes cell migration, proliferation, and matrix making through acceleration in angiogenesis. Growth factors in fibrin glue can stimulate and promote tissue repair. Autologous fibrin scaffolds are excellent candidates for tissue engineering so that they can be produced faster, cheaper, and in larger quantities. In addition, they are easy to use and the probability of viral or prion transmission may be decreased. Therefore, autologous fibrin glue appears to be promising scaffold in regenerative maxillofacial surgery.

  9. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome.

    Science.gov (United States)

    Kim, Tae Beom; Shim, Young Sup; Lee, Sang Min; Son, Eun Suk; Shim, Jung Woo; Lee, Sang Pyo

    2018-03-14

    Post-orgasmic illness syndrome (POIS) is a very rare disease characterized by local allergic symptoms and transient flu-like illness that nearly always occur after masturbation, coitus, or spontaneous ejaculation and last for 2 to 7 days. In a previous case report, 2 patients with POIS received hyposensitization therapy composed of multiple subcutaneous injections of autologous semen that resulted in a gradual decrease of symptoms. However, this procedure requires patients to endure pain and discomfort during frequent subcutaneous injections and preceding masturbations to obtain the autologous semen used for therapy. Recent studies have suggested that intralymphatic immunotherapy is a promising new method of allergen-specific immunotherapy against allergic diseases, showing a faster onset and longer duration of therapeutic effects after only several intralymphatic injections. We report on a case of a Korean man with POIS who received intralymphatic immunotherapy that alleviated POIS-related symptoms and in whom the existence of semen-specific immunoglobulin E was confirmed using immunoglobulin E immunoblotting and enzyme-linked immunosorbent assay. Kim TB, Shim YS, Lee, SM, et al. Intralymphatic Immunotherapy With Autologous Semen in a Korean Man With Post-Orgasmic Illness Syndrome. Sex Med 2018;X:XX-XX. Copyright © 2018. Published by Elsevier Inc.

  10. Treatment of therapy-refractive ulcera cruris of various origins with autologous keratinocytes in fibrin sealant.

    Science.gov (United States)

    Johnsen, S; Ermuth, T; Tanczos, E; Bannasch, H; Horch, R E; Zschocke, I; Peschen, M; Schöpf, E; Vanscheidt, W; Augustin, M

    2005-02-01

    Evaluation of the effects of cultivated, subconfluent, autologous keratinocytes in fibrin sealant (BioSeed-S) on the healing of therapy-refractive chronic wounds. Open observational study in 60 patients with chronic leg ulcers and impaired wound healing of various origins. After whole-skin excision and cultivation of the autologous keratinocytes, the suspended cells were applied to the preconditioned wound in fibrin sealant. Wound epithelization and wound size were recorded at defined times. Fifty-two of the 60 participating patients could be evaluated. After 6 weeks, 29 ulcers (55.8%) were healed. The mean epithelization increased between the 8th and 42nd postoperative day from 23% to 62.5%. In 50.0% of the patients, global assessment of the wound showed a high degree of epithelization or healing after 42 days. In 32.6% of treated patients, improvement was observed, while no healing tendency was to be found in 17.4%. The present observational study indicates that the transplantation of autologous keratinocytes suspended in fibrin sealant could be of advantage in the treatment of refractive leg ulcers.

  11. Prenatally engineered autologous amniotic fluid stem cell-based heart valves in the fetal circulation.

    Science.gov (United States)

    Weber, Benedikt; Emmert, Maximilian Y; Behr, Luc; Schoenauer, Roman; Brokopp, Chad; Drögemüller, Cord; Modregger, Peter; Stampanoni, Marco; Vats, Divya; Rudin, Markus; Bürzle, Wilfried; Farine, Marc; Mazza, Edoardo; Frauenfelder, Thomas; Zannettino, Andrew C; Zünd, Gregor; Kretschmar, Oliver; Falk, Volkmar; Hoerstrup, Simon P

    2012-06-01

    Prenatal heart valve interventions aiming at the early and systematic correction of congenital cardiac malformations represent a promising treatment option in maternal-fetal care. However, definite fetal valve replacements require growing implants adaptive to fetal and postnatal development. The presented study investigates the fetal implantation of prenatally engineered living autologous cell-based heart valves. Autologous amniotic fluid cells (AFCs) were isolated from pregnant sheep between 122 and 128 days of gestation via transuterine sonographic sampling. Stented trileaflet heart valves were fabricated from biodegradable PGA-P4HB composite matrices (n = 9) and seeded with AFCs in vitro. Within the same intervention, tissue engineered heart valves (TEHVs) and unseeded controls were implanted orthotopically into the pulmonary position using an in-utero closed-heart hybrid approach. The transapical valve deployments were successful in all animals with acute survival of 77.8% of fetuses. TEHV in-vivo functionality was assessed using echocardiography as well as angiography. Fetuses were harvested up to 1 week after implantation representing a birth-relevant gestational age. TEHVs showed in vivo functionality with intact valvular integrity and absence of thrombus formation. The presented approach may serve as an experimental basis for future human prenatal cardiac interventions using fully biodegradable autologous cell-based living materials. Copyright © 2012 Elsevier Ltd. All rights reserved.

  12. Autologous fat injection combined with palatoplasty and pharyngoplasty for velopharyngeal insufficiency and cleft palate: preliminary experience.

    Science.gov (United States)

    Cao, Yimei; Ma, Tingting; Wu, Di; Yin, Ningbei; Zhao, Zhenmin

    2013-08-01

    The aim was to evaluate clinical application of autologous fat transplantation in the posterior pharynx to treat velopharyngeal incompetence and cleft palate. Case series with chart review. Cleft Lip and Palate Center of Plastic Surgery Hospital, an academic medical center. We studied 11 patients (age, 5-26 years) with a cleft palate and velopharyngeal insufficiency who underwent autologous fat injection. Patients were followed for 9 to 40 months. Pronunciation evaluation, visual appearance of the palatopharyngeal area, nasopharyngeal fibroscopy (NPF), palatopharyngeal lateral radiography, and magnetic resonance imaging (MRI) were undertaken before and after the operation. Speech intelligibility was markedly increased in all patients. Pronunciation was good to excellent compared with the preoperative level (P = .001). Mean velopharyngeal insufficiency rate was significantly reduced from 26.05% to 6.96% (P = .028) by NPF and from 26.42% to 7.11% (P = .017) by MRI (axial plane). Magnetic resonance imaging indicated significantly reduced mean minimum velopharyngeal distance, from 10.39 to 3.65 mm (P = .012) in the sagittal plane, and markedly increased thickness of transplanted fat in the posterior pharyngeal wall (sagittal, 5.43 mm; axial, 4.74 mm). There were few complications (sleep apnea, nasopharyngeal regurgitation). Autologous fat transplantation in the posterior pharyngeal wall was a good method for treating velopharyngeal incompetence. The safety profile was good in our sample, and we got a consistent result in the follow-up period. In addition, it also could be combined with routine surgery.

  13. IMMUNE STATE IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AT LATE TERMS AFTER AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION

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    N. V. Minaeva

    2012-01-01

    Full Text Available Abstract. Autologous hematopoietic stem cell transplantation (auto-HSCT is one of the most effective methods for treatment of patients with various forms of hemoblastoses, both in adults and children. However, high-dose chemotherapy protocols used in this procedure are characterized by pronounced myeloand immunotoxicity. Appropriate data concerning immune state at long terms after high-dose chemotherapy and auto-HSCT are sparse and controversial, and there is no consensus on time dynamics of immune system reconstitution. The aim of this study was a comprehensive evaluation of immunity in recipients of auto-HSCT at longer terms. Clinical and immunological testing was performed in ninety-eight patients with hematological malignancies before starting a high-dose chemotherapy, and at late post-transplant period. The state of cellular immunity was assessed as expression of surface CD3+, CD4+, CD8+, CD16+, CD19+ lymphocyte antigens. Humoral immunity was evaluated by serum IgG, IgA, and IgM levels. The studies have revealed disorders of cellular and humoral immunity, as well as nonspecific immune resistance factors in recipients of autologous hematopoietic stem cells at late terms post-transplant. Immune reconstitution in patients receiving highdose consolidation treatment followed by auto-HSCT takes longer time than in patients who did not receive autologous hematopoietic stem cells. Severity of these disturbances and immune reconstitution rates depend on the type of conditioning regimen, and the source of haematopoietic stem cells used for transplantation.

  14. Effect of acetylsalicylic acid on microvascular thrombosis in autologous breast reconstruction.

    Science.gov (United States)

    Enajat, Morteza; Aziz Mohammadi, Mujzgan; Debeij, Jan; van der Hulst, Rene R W J; Mureau, Marc A M

    2014-01-01

    Although advances in microsurgery have increased success rates of autologous breast reconstruction, microvascular thrombosis still remains a major concern as a cause of flap failure. At present, no evidence-based guidelines on pharmacological prevention of microvascular thrombosis exist. This study investigates the effect of acetylsalicylic acid on the incidence of microvascular complications in patients undergoing autologous breast reconstruction. Patients undergoing deep inferior epigastric artery perforator or free transverse rectus abdominis myocutaneous flap breast reconstruction at two academic centers in the Netherlands between 2005 and 2011 were included. Patients at one center received once daily 0.6 mL of nadroparine and 40 mg acetylsalicylic acid, while patients at the other center received 0.6 mL nadroparine only. A total of 430 consecutive patients underwent 592 breast reconstructions. No statistically significant differences were found between the two groups in the incidence of flap failure (2.8 and 2.5%), microvascular thromboembolic complications (2.6 and 3.8%), venous congestion (3.4 and 2.8%), or overall complications (28.0 and 32.3%). Hematoma tended to occur more often in the group receiving acetylsalicylic acid (9.2 and 4.7%).It was found that no protective effect of acetylsalicylic acid on microvascular complications was present. Given its known risks and the somewhat increased occurrence of hematoma in the present study, we stopped to routinely administer acetylsalicylic acid after autologous breast reconstruction. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Restraint stress alters neutrophil and macrophage phenotypes during wound healing

    Science.gov (United States)

    Tymen, Stéphanie D.; Rojas, Isolde G.; Zhou, Xiaofeng; Fang, Zong Juan; Zhao, Yan; Marucha, Phillip T.

    2013-01-01

    Previous studies reported that stress delays wound healing, impairs bacterial clearance, and elevates the risk for opportunistic infection. Neutrophils and macrophages are responsible for the removal of bacteria present at the wound site. The appropriate recruitment and functions of these cells are necessary for efficient bacterial clearance. In our current study we found that restraint stress induced an excessive recruitment of neutrophils extending the inflammatory phase of healing, and the gene expression of neutrophil attracting chemokines MIP-2 and KC. However, restraint stress did not affect macrophage infiltration. Stress decreased the phagocytic abilities of phagocytic cells ex vivo, yet it did not affect superoxide production. The cell surface expression of adhesion molecules CD11b and TLR4 were decreased in peripheral blood monocytes in stressed mice. The phenotype of macrophages present at the wound site was also altered. Gene expression of markers of pro-inflammatory classically activated macrophages, CXCL10 and CCL5, were down-regulated; as were markers associated with wound healing macrophages, CCL22, IGF-1, RELMα; and the regulatory macrophage marker, chemokine CCL1. Restraint stress also induced up-regulation of IL10 gene expression. In summary, our study has shown that restraint stress suppresses the phenotype shift of the macrophage population, as compared to the changes observed during normal wound healing, while the number of macrophages remains constant. We also observed a general suppression of chemokine gene expression. Modulation of the macrophage phenotype could provide a new therapeutic approach in the treatment of wounds under stress conditions in the clinical setting. PMID:22884902

  16. Ginger extract inhibits LPS induced macrophage activation and function

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    Bruch David

    2008-01-01

    Full Text Available Abstract Background Macrophages play a dual role in host defence. They act as the first line of defence by mounting an inflammatory response to antigen exposure and also act as antigen presenting cells and initiate the adaptive immune response. They are also the primary infiltrating cells at the site of inflammation. Inhibition of macrophage activation is one of the possible approaches towards modulating inflammation. Both conventional and alternative approaches are being studied in this regard. Ginger, an herbal product with broad anti inflammatory actions, is used as an alternative medicine in a number of inflammatory conditions like rheumatic disorders. In the present study we examined the effect of ginger extract on macrophage activation in the presence of LPS stimulation. Methods Murine peritoneal macrophages were stimulated by LPS in presence or absence of ginger extract and production of proinflammatory cytokines and chemokines were observed. We also studied the effect of ginger extract on the LPS induced expression of MHC II, B7.1, B7.2 and CD40 molecules. We also studied the antigen presenting function of ginger extract treated macrophages by primary mixed lymphocyte reaction. Results We observed that ginger extract inhibited IL-12, TNF-α, IL-1β (pro inflammatory cytokines and RANTES, MCP-1 (pro inflammatory chemokines production in LPS stimulated macrophages. Ginger extract also down regulated the expression of B7.1, B7.2 and MHC class II molecules. In addition ginger extract negatively affected the antigen presenting function of macrophages and we observed a significant reduction in T cell proliferation in response to allostimulation, when ginger extract treated macrophages were used as APCs. A significant decrease in IFN-γ and IL-2 production by T cells in response to allostimulation was also observed. Conclusion In conclusion ginger extract inhibits macrophage activation and APC function and indirectly inhibits T cell activation.

  17. Btk regulates macrophage polarization in response to lipopolysaccharide.

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    Joan Ní Gabhann

    Full Text Available Bacterial Lipopolysaccharide (LPS is a strong inducer of inflammation and does so by inducing polarization of macrophages to the classic inflammatory M1 population. Given the role of Btk as a critical signal transducer downstream of TLR4, we investigated its role in M1/M2 induction. In Btk deficient (Btk (-\\- mice we observed markedly reduced recruitment of M1 macrophages following intraperitoneal administration of LPS. Ex vivo analysis demonstrated an impaired ability of Btk(-/- macrophages to polarize into M1 macrophages, instead showing enhanced induction of immunosuppressive M2-associated markers in response to M1 polarizing stimuli, a finding accompanied by reduced phosphorylation of STAT1 and enhanced STAT6 phosphorylation. In addition to STAT activation, M1 and M2 polarizing signals modulate the expression of inflammatory genes via differential activation of transcription factors and regulatory proteins, including NF-κB and SHIP1. In keeping with a critical role for Btk in macrophage polarization, we observed reduced levels of NF-κB p65 and Akt phosphorylation, as well as reduced induction of the M1 associated marker iNOS in Btk(-/- macrophages in response to M1 polarizing stimuli. Additionally enhanced expression of SHIP1, a key negative regulator of macrophage polarisation, was observed in Btk(-/- macrophages in response to M2 polarizing stimuli. Employing classic models of allergic M2 inflammation, treatment of Btk (-/- mice with either Schistosoma mansoni eggs or chitin resulted in increased recruitment of M2 macrophages and induction of M2-associated genes. This demonstrates an enhanced M2 skew in the absence of Btk, thus promoting the development of allergic inflammation.

  18. HIV-1 activates macrophages independent of Toll-like receptors.

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    Joseph N Brown

    Full Text Available Macrophages provide an interface between innate and adaptive immunity and are important long-lived reservoirs for Human Immunodeficiency Virus Type-1 (HIV-1. Multiple genetic networks involved in regulating signal transduction cascades and immune responses in macrophages are coordinately modulated by HIV-1 infection.To evaluate complex interrelated processes and to assemble an integrated view of activated signaling networks, a systems biology strategy was applied to genomic and proteomic responses by primary human macrophages over the course of HIV-1 infection. Macrophage responses, including cell cycle, calcium, apoptosis, mitogen-activated protein kinases (MAPK, and cytokines/chemokines, to HIV-1 were temporally regulated, in the absence of cell proliferation. In contrast, Toll-like receptor (TLR pathways remained unaltered by HIV-1, although TLRs 3, 4, 7, and 8 were expressed and responded to ligand stimulation in macrophages. HIV-1 failed to activate phosphorylation of IRAK-1 or IRF-3, modulate intracellular protein levels of Mx1, an interferon-stimulated gene, or stimulate secretion of TNF, IL-1beta, or IL-6. Activation of pathways other than TLR was inadequate to stimulate, via cross-talk mechanisms through molecular hubs, the production of proinflammatory cytokines typical of a TLR response. HIV-1 sensitized macrophage responses to TLR ligands, and the magnitude of viral priming was related to virus replication.HIV-1 induced a primed, proinflammatory state, M1(HIV, which increased the responsiveness of macrophages to TLR ligands. HIV-1 might passively evade pattern recognition, actively inhibit or suppress recognition and signaling, or require dynamic interactions between macrophages and other cells, such as lymphocytes or endothelial cells. HIV-1 evasion of TLR recognition and simultaneous priming of macrophages may represent a strategy for viral survival, contribute to immune pathogenesis, and provide important targets for therapeutic

  19. Rediscovering peritoneal macrophages in a murine endometriosis model.

    Science.gov (United States)

    Yuan, Ming; Li, Dong; An, Min; Li, Qiuju; Zhang, Lu; Wang, Guoyun

    2017-01-01

    What are the features of peritoneal macrophage subgroups and T helper cells in the development of murine endometriosis? During the development of endometriosis in a murine model, large peritoneal macrophages (LPMs) and small peritoneal macrophages (SPMs) are polarized into M1 and M2 cells, respectively, and the proportions of T helper (Th) 1, Th17 and T regulatory (T reg ) cells are increased. Numerous studies investigating the etiology and pathogenesis of endometriosis have focused on the polarization states of peritoneal macrophages in endometriosis models and patients, but the results are inconclusive. Further studies indicate that peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs, although their roles in endometriosis are unknown. This study involves a prospective and randomized experiment. Fifty C57BL/6 female mice were randomly allocated to five control and five experimental groups (n = 5/group) according to the presence or absence of transplantation. The transplant periods are 0.25, 3, 14, 28 and 42 days. C57BL/6 mice were utilized to establish an endometriosis model by i.p. injection of allogeneic endometrial segments. Dynamic changes of peritoneal macrophage subsets and polarization profiles were evaluated by flow cytometry (FCM). Macrophage morphology and density were assessed by cell counting under a microscope. Dynamic changes of Th1, Th2, Th17 and T reg cells were estimated by FCM. Peritoneal macrophages are composed of two distinct subsets: LPMs and SPMs. The proportion of SPMs increased immediately after peritoneal injection of endometrial tissues, whereas LPMs showed an opposite trend. Peritoneal macrophages differentiated into both M1 and M2 macrophages. The bidirectional polarization of macrophages was caused by the inverse trends of polarization of LPMs and SPMs. Consistently, the proportions of Th1, Th17 and T reg cells were all increased in mice with endometriosis. N/A. In this study, detection was only performed in a

  20. The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

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    Se-Jin Jeong

    2017-03-01

    Full Text Available Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

  1. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages

    NARCIS (Netherlands)

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klueter, Harald; Gratchev, Alexei; Harmsen, Martin C.; Kzhyshkowska, Julia

    2017-01-01

    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in

  2. Human Induced Pluripotent Stem Cell-Derived Macrophages Share Ontogeny with MYB-Independent Tissue-Resident Macrophages

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    Julian Buchrieser

    2017-02-01

    Full Text Available Tissue-resident macrophages, such as microglia, Kupffer cells, and Langerhans cells, derive from Myb-independent yolk sac (YS progenitors generated before the emergence of hematopoietic stem cells (HSCs. Myb-independent YS-derived resident macrophages self-renew locally, independently of circulating monocytes and HSCs. In contrast, adult blood monocytes, as well as infiltrating, gut, and dermal macrophages, derive from Myb-dependent HSCs. These findings are derived from the mouse, using gene knockouts and lineage tracing, but their applicability to human development has not been formally demonstrated. Here, we use human induced pluripotent stem cells (iPSCs as a tool to model human hematopoietic development. By using a CRISPR-Cas9 knockout strategy, we show that human iPSC-derived monocytes/macrophages develop in an MYB-independent, RUNX1-, and SPI1 (PU.1-dependent fashion. This result makes human iPSC-derived macrophages developmentally related to and a good model for MYB-independent tissue-resident macrophages, such as alveolar and kidney macrophages, microglia, Kupffer cells, and Langerhans cells.

  3. Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

    Science.gov (United States)

    Miwa, Shinji; Nishida, Hideji; Tanzawa, Yoshikazu; Takeuchi, Akihiko; Hayashi, Katsuhiro; Yamamoto, Norio; Mizukoshi, Eishiro; Nakamoto, Yasunari; Kaneko, Shuichi; Tsuchiya, Hiroyuki

    2017-05-01

    There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed. In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively. Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society. © 2017 American Cancer Society.

  4. Macrophage traits in cancer cells are induced by macrophage-cancer cell fusion and cannot be explained by cellular interaction.

    Science.gov (United States)

    Shabo, Ivan; Midtbö, Kristine; Andersson, Henrik; Åkerlund, Emma; Olsson, Hans; Wegman, Pia; Gunnarsson, Cecilia; Lindström, Annelie

    2015-11-20

    Cell fusion is a natural process in normal development and tissue regeneration. Fusion between cancer cells and macrophages generates metastatic hybrids with genetic and phenotypic characteristics from both maternal cells. However, there are no clinical markers for detecting cell fusion in clinical context. Macrophage-specific antigen CD163 expression in tumor cells is reported in breast and colorectal cancers and proposed being caused by macrophages-cancer cell fusion in tumor stroma. The purpose of this study is to examine the cell fusion process as a biological explanation for macrophage phenotype in breast. Monocytes, harvested from male blood donor, were activated to M2 macrophages and co-cultured in ThinCert transwell system with GFP-labeled MCF-7 cancer cells. MCF7/macrophage hybrids were generated by spontaneous cell fusion, isolated by fluorescence-activated cell sorting and confirmed by fluorescence microscopy, short tandem repeats analysis and flow cytometry. CD163 expression was evaluated in breast tumor samples material from 127 women by immunohistochemistry. MCF-7/macrophage hybrids were generated spontaneously at average rate of 2 % and showed phenotypic and genetic traits from both maternal cells. CD163 expression in MCF-7 cells could not be induced by paracrine interaction with M2-activated macrophages. CD163 positive cancer cells in tumor sections grew in clonal collection and a cutoff point >25 % of positive cancer cells was significantly correlated to disease free and overall survival. In conclusion, macrophage traits in breast cancer might be caused by cell fusion rather than explained by paracrine cellular interaction. These data provide new insights into the role of cell fusion in breast cancer and contributes to the development of clinical markers to identify cell fusion.

  5. Macrophage ABCA2 deletion modulates intracellular cholesterol deposition, affects macrophage apoptosis, and decreases early atherosclerosis in LDL receptor knockout mice.

    Science.gov (United States)

    Calpe-Berdiel, Laura; Zhao, Ying; de Graauw, Marjo; Ye, Dan; van Santbrink, Peter J; Mommaas, A Mieke; Foks, Amanda; Bot, Martine; Meurs, Illiana; Kuiper, Johan; Mack, Jody T; Van Eck, Miranda; Tew, Kenneth D; van Berkel, Theo J C

    2012-08-01

    The ABCA2 transporter shares high structural homology to ABCA1, which is crucial for the removal of excess cholesterol from macrophages and, by extension, in atherosclerosis. It has been suggested that ABCA2 sequesters cholesterol inside the lysosomes, however, little is known of the macrophage-specific role of ABCA2 in regulating lipid homeostasis in vivo and in modulating susceptibility to atherosclerosis. Chimeras with dysfunctional macrophage ABCA2 were generated by transplantation of bone marrow from ABCA2 knockout (KO) mice into irradiated LDL receptor (LDLr) KO mice. Interestingly, lack of ABCA2 in macrophages resulted in a diminished lesion size in the aortic root (-24.5%) and descending thoracic aorta (-36.6%) associated with a 3-fold increase in apoptotic cells, as measured by both caspase 3 and TUNEL. Upon oxidized LDL exposure, macrophages from wildtype (WT) transplanted animals developed filipin-positive droplets in lysosomal-like compartments, corresponding to free cholesterol (FC) accumulation. In contrast, ABCA2-deficient macrophages displayed an abnormal diffuse distribution of FC over peripheral regions. The accumulation of neutral sterols in lipid droplets was increased in ABCA2-deficient macrophages, but primarily in cytoplasmic clusters and not in lysosomes. Importantly, apoptosis of oxLDL loaded macrophages lacking ABCA2 was increased 2.7-fold, probably as a consequence of the broad cellular distribution of FC. Lack of functional ABCA2 generates abnormalities in intracellular lipid distribution/trafficking in macrophages consistent with its lysosomal sequestering role, leading to an increased susceptibility to apoptosis in response to oxidized lipids and reduced atherosclerotic lesion development. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  6. Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage-laden gelatine hydrogels.

    Science.gov (United States)

    Dollinger, Camille; Ciftci, Sait; Knopf-Marques, Helena; Guner, Rabia; Ghaemmaghami, Amir M; Debry, Christian; Barthes, Julien; Vrana, Nihal Engin

    2018-02-01

    The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in-vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP-1 monocytes, endothelial cells and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP-1 cells were encapsulated in the presence or absence of IL-4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage-laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes-laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro- and anti-inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation. Copyright © 2017 John Wiley & Sons, Ltd.

  7. A Nationwide Analysis of Cost Variation for Autologous Free Flap Breast Reconstruction.

    Science.gov (United States)

    Billig, Jessica I; Lu, Yiwen; Momoh, Adeyiza O; Chung, Kevin C

    2017-11-01

    Cost variation among hospitals has been demonstrated for surgical procedures. Uncovering these differences has helped guide measures taken to reduce health care spending. To date, the fiscal consequence of hospital variation for autologous free flap breast reconstruction is unknown. To investigate factors that influence cost variation for autologous free flap breast reconstruction. A secondary cross-sectional analysis was performed using the Healthcare Cost and Utilization Project National Inpatient Sample database from 2008 to 2010. The dates of analysis were September 2016 to February 2017. The setting was a stratified sample of all US community hospitals. Participants were female patients who were diagnosed as having breast cancer or were at high risk for breast cancer and underwent autologous free flap breast reconstruction. Variables of interest included demographic data, hospital characteristics, length of stay, complications (surgical and systemic), and inpatient cost. The study used univariate and generalized linear mixed models to examine associations between patient and hospital characteristics and cost. A total of 3302 patients were included in the study, with a median age of 50 years (interquartile range, 44-57 years). The mean cost for autologous free flap breast reconstruction was $22 677 (interquartile range, $14 907-$33 391). Flap reconstructions performed at high-volume hospitals were significantly more costly than those performed at low-volume hospitals ($24 360 vs $18 918, P cost (Exp[β], 1.06; 95% CI, 1.02-1.11; P = .003). Fewer surgical complications (16.4% [169 of 1029] vs 23.7% [278 of 1174], P cost variation among patients undergoing autologous free flap breast reconstruction. Experience, as measured by a hospital's volume, provides quality health care with fewer complications but is more costly. Longer length of stay contributed to regional cost variation and may be a target for decreasing expenditure, without

  8. Evaluation of ex vivo produced endothelial progenitor cells for autologous transplantation in primates.

    Science.gov (United States)

    Qin, Meng; Guan, Xin; Zhang, Yu; Shen, Bin; Liu, Fang; Zhang, Qingyu; Ma, Yupo; Jiang, Yongping

    2018-01-22

    Autologous transplantation of endothelial progenitor cells (EPCs) is a promising therapeutic approach in the treatment of various vascular diseases. We previously reported a two-step culture system for scalable generation of human EPCs derived from cord blood CD34 + cells ex vivo. Here, we now apply this culture system to expand and differentiate human and nonhuman primate EPCs from mobilized peripheral blood (PB) CD34 + cells for the therapeutic potential of autologous transplantation. The human and nonhuman primate EPCs from mobilized PB CD34 + cells were cultured according to our previously reported system. The generated adherent cells were then characterized by the morphology, surface markers, nitric oxide (NO)/endothelial NO synthase (eNOS) levels and Dil-acetylated low-density lipoprotein (Dil-Ac-LDL) uptake/fluorescein isothiocyanate (FITC)-lectin binding actives. Furthermore, the efficacy and safety studies were performed by autologous transplantation via hepatic portal vein injection in a nonhuman primate model with acute liver sinusoidal endothelial cell injury. The mobilized PB CD34 + cells from both human and nonhuman primate were efficiently expanded and differentiated. Over 2 × 10 8 adherent cells were generated from 20 mL mobilized primate PB (1.51 × 10 6  ± 3.39 × 10 5 CD34 + cells) by 36-day culture and more than 80% of the produced cells were identified as EPCs/endothelial cells (ECs). In the autologous transplant model, the injected EPC/ECs from nonhuman primate PB were scattered in the intercellular spaces of hepatocytes at the hepatic tissues 14 days post-transplantation, indicating successful migration and reconstitution in the liver structure as the functional EPCs/ECs. We successfully applied our previous two-step culture system for the generation of primate EPCs from mobilized PB CD34 + cells, evaluated the phenotypes ex vivo, and transplanted autologous EPCs/ECs in a nonhuman primate model. Our study indicates that

  9. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV.

    Science.gov (United States)

    Tebas, Pablo; Stein, David; Tang, Winson W; Frank, Ian; Wang, Shelley Q; Lee, Gary; Spratt, S Kaye; Surosky, Richard T; Giedlin, Martin A; Nichol, Geoff; Holmes, Michael C; Gregory, Philip D; Ando, Dale G; Kalos, Michael; Collman, Ronald G; Binder-Scholl, Gwendolyn; Plesa, Gabriela; Hwang, Wei-Ting; Levine, Bruce L; June, Carl H

    2014-03-06

    CCR5 is the major coreceptor for human immunodeficiency virus (HIV). We investigated whether site-specific modification of the gene ("gene editing")--in this case, the infusion of autologous CD4 T cells in which the CCR5 gene was rendered permanently dysfunctional by a zinc-finger nuclease (ZFN)--is safe. We enrolled 12 patients in an open-label, nonrandomized, uncontrolled study of a single dose of ZFN-modified autologous CD4 T cells. The patients had chronic aviremic HIV infection while they were receiving highly active antiretroviral therapy. Six of them underwent an interruption in antiretroviral treatment 4 weeks after the infusion of 10 billion autologous CD4 T cells, 11 to 28% of which were genetically modified with the ZFN. The primary outcome was safety as assessed by treatment-related adverse events. Secondary outcomes included measures of immune reconstitution and HIV resistance. One serious adverse event was associated with infusion of the ZFN-modified autologous CD4 T cells and was attributed to a transfusion reaction. The median CD4 T-cell count was 1517 per cubic millimeter at week 1, a significant increase from the preinfusion count of 448 per cubic millimeter (PCCR5-modified CD4 T cells at 1 week was 250 cells per cubic millimeter. This constituted 8.8% of circulating peripheral-blood mononuclear cells and 13.9% of circulating CD4 T cells. Modified cells had an estimated mean half-life of 48 weeks. During treatment interruption and the resultant viremia, the decline in circulating CCR5-modified cells (-1.81 cells per day) was significantly less than the decline in unmodified cells (-7.25 cells per day) (P=0.02). HIV RNA became undetectable in one of four patients who could be evaluated. The blood level of HIV DNA decreased in most patients. CCR5-modified autologous CD4 T-cell infusions are safe within the limits of this study. (Funded by the National Institute of Allergy and Infectious Diseases and others; ClinicalTrials.gov number, NCT00842634.).

  10. Efficacy of autologous conjunctival flap on repairing the late-onset filtering bleb leakage

    Directory of Open Access Journals (Sweden)

    Jian-Gang Xu

    2018-04-01

    Full Text Available AIM: To evaluate the effectiveness of autologous conjunctival flap surgery for repairing the late-onset filtering bleb leakage after trabeculectomy. METHODS: This study retrospectively reviewed 106 eyes from 106 patients with late-onset filtering bleb leakage after trabeculectomy who received autologous conjunctival flap surgery at the Zhongshan Ophthalmic Centre from 2005 to 2015. The basic information was recorded, and the interval time between trabeculectomy and autologous conjunctival flap surgery as well as related risk factors, intraocular pressure (IOP, anterior chamber depth (ACD and best corrected visual acuity (BCVA were analysed. Moreover, 41 patients who completed the 1-year follow up were analysed to determine the IOP and BCVA changes and long-term success rates. RESULTS: The 50 male and 56 female subjects (average age 39.13±17.96y included 47 (44.34% and 33 (31.13% cases of primary open angle and primary angle-closure glaucoma. The mean interval between trabeculectomy and repair surgery was 60.60±56.92 (3-264mo. The mean mitomycin (MMC concentration during trabeculectomy was 0.27±0.04 (0.12-0.4 mg/mL in the fornix-based conjunctival flap group (68 patients and 0.28±0.04 (0.20-0.33 mg/mL in the limbal-based conjunctival flap group (11 patients. After bleb leakage, the patients' vision remained stable while the IOP decreased from 10.25±4.76 (3-20.86 to 9.44±4.33 (2-21 mm Hg (P<0.01. In the 41 analysed patients, the IOP was controlled at 15.68±5.11 (7-40 mm Hg in the 1st year after autologous conjunctival flap surgery and recurrence was not observed, for a long-term success rate of 100%. CONCLUSION: Autologous conjunctival flap repairing surgery is an effective technique for sealing filtering bleb leakages and controlling IOP postoperatively.

  11. Role of bone marrow macrophages in controlling homeostasis and repair in bone and bone marrow niches.

    Science.gov (United States)

    Kaur, Simranpreet; Raggatt, Liza Jane; Batoon, Lena; Hume, David Arthur; Levesque, Jean-Pierre; Pettit, Allison Robyn

    2017-01-01

    Macrophages, named for their phagocytic ability, participate in homeostasis, tissue regeneration and inflammatory responses. Bone and adjacent marrow contain multiple functionally unique resident tissue macrophage subsets which maintain and regulate anatomically distinct niche environments within these interconnected tissues. Three subsets of bone-bone marrow resident tissue macrophages have been characterised; erythroblastic island macrophages, haematopoietic stem cell niche macrophages and osteal macrophages. The role of these macrophages in controlling homeostasis and repair in bone and bone marrow niches is reviewed in detail. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Effect of Platelet-Rich Plasma (PRP) versus Autologous Whole Blood on Pain and Function Improvement in Tennis Elbow: A Randomized Clinical Trial

    OpenAIRE

    Raeissadat, Seyed Ahmad; Sedighipour, Leyla; Rayegani, Seyed Mansoor; Bahrami, Mohammad Hasan; Bayat, Masume; Rahimi, Rosa

    2014-01-01

    Background. Autologous whole blood and platelet-rich plasma (PRP) have been both suggested to treat chronic tennis elbow. The aim of the present study was to compare the effects of PRP versus autologous whole blood local injection in chronic tennis elbow. Methods. Forty patients with tennis elbow were randomly divided into 2 groups. Group 1 was treated with a single injection of 2 mL of autologous PRP and group 2 with 2 mL of autologous blood. Tennis elbow strap, stretching, and strengthening...

  13. Early resumption of physical activities leads to inferior clinical outcomes after matrix-based autologous chondrocyte implantation in the knee.

    Science.gov (United States)

    Niethammer, Thomas R; Müller, Peter E; Safi, Elem; Ficklscherer, Andreas; Roßbach, Björn P; Jansson, Volkmar; Pietschmann, Matthias F

    2014-06-01

    Matrix-based autologous chondrocyte implantation is a well-established operation procedure for full cartilage defects. When to resume physical activity after matrix-based autologous chondrocyte implantation is controversial. Our hypothesis was that early resumption of physical activity leads to a worse clinical outcome after matrix-based autologous chondrocyte implantation in the knee two years post-operatively. Physical activity is defined as any kind of impact sport. Forty-four patients with cartilage defects of the knee were treated with matrix-based autologous chondrocyte implantation (Novocart3D). All patients were assessed preoperatively and after a period of 24 months with the University of California Los Angeles (UCLA) Activity score. The return to physical activities or sports after matrix-based autologous chondrocyte implantation was documented. Patients were evaluated using the International Knee Documentation Committee Knee Examination Form and visual analogue scale for pain after 6, 12 and 24 months. Fifty-five percent showed an unchanged level of physical activity in the UCLA Activity score post-operatively. About 35% showed a lower level and 10% a higher level of physical activity. The average return to physical activities or sports after matrix-based autologous chondrocyte implantation procedure was 10.2 months. Patients with a later return of sports after 12 months showed significantly better clinical results after two years. In particular, patients who started practicing impact sport after 12 months post-operatively showed significantly better results. Resuming physical activity including impact sports without waiting at least 12 months after the operation leads to inferior outcomes up to 24 months after matrix-based autologous chondrocyte implantation. Level IV.

  14. Comparison of autologous versus allogeneic epithelial-like stem cell treatment in an in vivo equine skin wound model.

    Science.gov (United States)

    Broeckx, Sarah Y; Borena, Bizunesh M; Van Hecke, Lore; Chiers, Koen; Maes, Sofie; Guest, Deborah J; Meyer, Evelyne; Duchateau, Luc; Martens, Ann; Spaas, Jan H

    2015-10-01

    Several studies report beneficial effects of autologous and allogeneic stem cells on wound healing. However, no comparison between autologous versus allogeneic epithelial-like stem cells (EpSCs) has been made so far. For this reason, we first hypothesize that both EpSC types enhance wound healing in comparison to vehicle treatment and untreated controls. Second, on the basis of other studies, we hypothesized that there would be no difference between autologous and allogeneic EpSCs. Twelve full-thickness skin wounds were created in six horses. Each horse was subjected to (i) autologous EpSCs, (ii) allogeneic EpSCs, (iii) vehicle treatment or (iv) untreated control. Wound evaluation was performed at day 3, 7 and 14 through wound exudates and at week 1, 2 and 5 through biopsies. Wound circumference and surface were significantly smaller in autologous EpSC-treated wounds. A significantly lower amount of total granulation tissue (overall) and higher vascularization (week 1) was observed after both EpSC treatments. Significantly more major histocompatibility complex II-positive and CD20-positive cells were noticed in EpSC-treated wounds at week 2. In autologous and allogeneic groups, the number of EpSCs in center biopsies was low after 1 week (11.7% and 6.1%), decreased to 7.6% and 1.7%, respectively (week 2), and became undetectable at week 5. These results confirm the first hypothesis and partially support the second hypothesis. Besides macroscopic improvements, both autologous and allogeneic EpSCs had similar effects on granulation tissue formation, vascularization and early cellular immune response. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  15. Macrophage migration inhibitory factor and autism spectrum disorders

    NARCIS (Netherlands)

    Grigorenko, Elena L.; Han, Summer S.; Yrigollen, Carolyn M.; Leng, Lin; Mizue, Yuka; Anderson, George M.; Mulder, Erik J.; de Bildt, Annelies; Minderaa, Ruud B.; Volkmar, Fred R.; Chang, Joseph T.; Bucala, Richard

    OBJECTIVE. Autistic spectrum disorders are childhood neurodevelopmental disorders characterized by social and communicative impairment and repetitive and stereotypical behavior. Macrophage migration inhibitory factor (MIF) is an upstream regulator of innate immunity that promotes

  16. EVIDENCE FOR THE MACROPHAGE INDUCING GENE IN MYCOBACTERIUM INTRACELLULARE

    Science.gov (United States)

    Background: The Mycobacterium avium Complex (MAC) includes the species M. avium (MA), M. intracellulare (MI), and possibly others. Organisms belonging to the MAC are phylogenetically closely related, opportunistic pathogens. The macrophage inducing gene (mig) is the only well-des...

  17. Macrophages, meta-inflammation, and immuno-metabolism.

    Science.gov (United States)

    Shapiro, Haim; Lutaty, Aviv; Ariel, Amiram

    2011-01-01

    Current research depicts specific modes of immunity and energy metabolism as being interrelated at the molecular, cellular, organ and organism level. Hence, whereas M2 (alternatively-activated) macrophages dominate insulin-sensitive adipose tissue in the lean, M1-skewed (classically-activated) macrophages accumulate in parallel to adiposity in the obese, and promote inflammation and insulin resistance, that is, meta-inflammation. The latest frontier of immuno-metabolism explores the coregulation of energy metabolism and immune function within hematopoietic cells. M1-skewed macrophages are sustained in edematous, hypoxic tissues by anaerobic glycolysis, whereas mitochondrial biogenesis and respiration dominates in M2 cells. We review the underlying mechanisms and the consequences of the transition from M2 to M1 predominance in adipose tissue, as well as the extracellular signals and transcription factors that control macrophage phenotypes and impose distinct metabolic modes.

  18. Expressions of macrophage migration inhibitory factor in patients ...

    African Journals Online (AJOL)

    ESRD) and is responsible for high mortality rates and increased left ventricular mass index (LVMI). Macrophage migration inhibitory factor (MIF) promotes inflammation and is an important factor in uremic cardiomyopathy. Aims: The aim of this study ...

  19. Monocytes and Macrophages in Pregnancy and Pre-Eclampsia

    Science.gov (United States)

    Faas, Marijke M.; Spaans, Floor; De Vos, Paul

    2014-01-01

    Preeclampsia is an important complication in pregnancy, characterized by hypertension and proteinuria in the second half of pregnancy. Generalized activation of the inflammatory response is thought to play a role in the pathogenesis of pre-eclampsia. Monocytes may play a central role in this inflammatory response. Monocytes are short lived cells that mature in the circulation and invade into tissues upon an inflammatory stimulus and develop into macrophages. Macrophages are abundantly present in the endometrium and play a role in implantation and placentation in normal pregnancy. In pre-eclampsia, these macrophages appear to be present in larger numbers and are also activated. In the present review, we focused on the role of monocytes and macrophages in the pathophysiology of pre-eclampsia. PMID:25071761

  20. Evaluation of in vitro macrophage differentiation during space flight

    Data.gov (United States)

    National Aeronautics and Space Administration — We differentiated mouse bone marrow cells in the presence of recombinant macrophage colony stimulating (rM-CSF) factor for 14 days during the flight of space shuttle...