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Transplantation Induction

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https://www.readbyqxmd.com/read/28544604/thymic-peripheral-crosstalk-in-lymphodepletion-therapy
#1
EDITORIAL
M E Snyder, D L Farber
T cell depletion is widely used as induction therapy in solid organ transplants and particularly in kidney transplantation, to reduce the episodes of acute cellular rejection. The resultant reduction in T cell numbers is usually temporary, as T cells are actively replenished due to thymic output and/or lymphopenia-induced proliferation of remaining, depletion-resistant T cells. However, the extent of T cell replenishment and the persistence of lymphopenia varies between individuals, with potential impacts on protective or pathogenic immune responses...
May 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28541773/induction-of-salivary-gland-like-cells-from-dental-follicle-epithelial-cells
#2
Q L Xu, A Furuhashi, Q Z Zhang, C M Jiang, T-H Chang, A D Le
The dental follicle (DF), most often associated with unerupted teeth, is a condensation of ectomesenchymal cells that surrounds the tooth germ in early stages of tooth development. In the present study, we aim to isolate epithelial stem-like cells from the human DF and explore their potential differentiation into salivary gland (SG) cells. We demonstrated the expression of stem cell-related genes in the epithelial components of human DF tissues, and these epithelial progenitor cells could be isolated and ex vivo expanded in a reproducible manner...
May 1, 2017: Journal of Dental Research
https://www.readbyqxmd.com/read/28540755/persistent-cytogenetic-abnormalities-in-patients-undergoing-intensive-chemotherapy-for-acute-myeloid-leukemia
#3
Lalit Saini, Joseph Brandwein, Artur Szkotak, Sunita Ghosh, Irwindeep Sandhu
We evaluated the impact of bone marrow sample characteristics on the detection of persistent cytogenetic abnormalities (PCA) following induction chemotherapy for acute myeloid leukemia (AML). PCA's were identified in 20.4% of patients and were more common with complete remission without count recovery (CRi) vs. those with count recovery (CR, 45.8 vs. 13.5%, p = .001), with  >2% blasts vs.  ≤2% blasts (42 vs. 12%, p =  .001) and with hypocellular trephine biopsies relative to those with normo/hypercellular biopsies (42...
May 25, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28539427/tlr-induced-murine-dendritic-cell-dc-activation-requires-dc-intrinsic-complement
#4
Joong-Hyuk Sheen, Michael G Strainic, Jinbo Liu, Weijia Zhang, Zhengzi Yi, M Edward Medof, Peter S Heeger
Induction of proinflammatory T cell immunity is augmented by innate dendritic cell (DC) maturation commonly initiated by TLR signaling. We demonstrate that ligation of TLR3, TLR4, and TLR9 induces murine DC production of complement components and local production of the anaphylatoxin C5a. In vitro, ex vivo, and in vivo analyses show that TLR-induced DC maturation, as assessed by surface phenotype, expression profiling by gene array, and functional ability to stimulate T cell responses, requires autocrine C3a receptor and C5a receptor (C3ar1/C5ar1) signaling...
May 24, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28538090/late-effects-in-pediatric-high-risk-neuroblastoma-survivors-after-intensive-induction-chemotherapy-followed-by-myeloablative-consolidation-chemotherapy-and-triple-autologous-stem-cell-transplants
#5
Amy E Armstrong, Karina Danner-Koptik, Shannon Golden, Jennifer Schneiderman, Morris Kletzel, Jennifer Reichek, Yasmin Gosiengfiao
Multimodal treatment in high-risk neuroblastoma has modestly improved survival; limited data exist on the late effects from these regimens. We report the sequelae of treatment incorporating 3 consecutive cycles of high-dose therapy and autologous stem cell transplants (ASCTs) without the use of total body irradiation (TBI). We reviewed the medical records of 61 patients treated on or following the Chicago Pilot 2 protocol between 1991 and 2008. Of the 25 patients who are alive (41%), 19 had near complete data to report...
May 23, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28535778/exosomes-from-mesenchymal-stem-cells-induce-the-conversion-of-hepatocytes-into-progenitor-oval-cells
#6
Hao-Hsiang Wu, Oscar K Lee
BACKGROUND: We previously reported that mesenchymal stem cells (MSCs) possess therapeutic effects in a murine model of carbon tetrachloride-induced acute liver failure. In the study, we observed that the majority of repopulated hepatocytes were of recipient origin and were adjacent to transplanted MSCs; only a low percentage of repopulated hepatocytes were from transplanted MSCs. The findings indicate that MSCs guided the formation of new hepatocytes. Exosomes are important messengers for paracrine signaling delivery...
May 23, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28534953/proteomic-analysis-of-differentially-expressed-proteins-in-kidneys-of-brain-dead-rabbits
#7
Ling Li, Ning Li, Chongxiang He, Wei Huang, Xiaoli Fan, Zibiao Zhong, Yanfeng Wang, Qifa Ye
A large number of previous clinical studies have reported a delayed graft function for brain dead donors, when compared with living relatives or cadaveric organ transplantations. However, there is no accurate method for the quality evaluation of kidneys from brain‑dead donors. In the present study, two‑dimensional gel electrophoresis and MALDI‑TOF MS‑based comparative proteomic analysis were conducted to profile the differentially‑expressed proteins between brain death and the control group renal tissues...
May 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28534310/combination-immunotherapy-for-type-1-diabetes
#8
REVIEW
Robert N Bone, Carmella Evans-Molina
PURPOSE OF REVIEW: Type 1 diabetes (T1D) is an autoimmune disease marked by β-cell destruction. Immunotherapies for T1D have been investigated since the 1980s and have focused on restoration of tolerance, T cell or B cell inhibition, regulatory T cell (Treg) induction, suppression of innate immunity and inflammation, immune system reset, and islet transplantation. The purpose of this review is to provide an overview and lessons learned from single immunotherapy trials, describe recent and ongoing combination immunotherapy trials, and provide perspectives on strategies for future combination clinical interventions aimed at preserving insulin secretion in T1D...
July 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28532396/addition-of-rituximab-to-chop-like-chemotherapy-in-first-line-treatment-of-primary-mediastinal-b-cell-lymphoma
#9
K Lisenko, G Dingeldein, M Cremer, M Kriegsmann, A D Ho, M Rieger, M Witzens-Harig
BACKGROUND: The addition of rituximab (R) to CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) -like therapy has improved survival in primary mediastinal B-cell lymphoma (PMBCL) patients. However, these results were obtained in young low risk patients and a reevaluation in an unselected patient cohort is warranted. METHODS: In this study, we analyzed 80 PMBCL patients treated with a CHOP-based regimen with and without rituximab. RESULTS: In the non-rituximab cohort 10-year progression free survival (PFS) was 67% and 10-year overall survival (OS) was 72% versus a PFS of 95% and a OS of 92% in the rituximab group, PFS P = 0...
May 22, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28529840/adoptive-cell-therapy-with-tregs-to-improve-transplant-outcomes-the-promise-and-the-stumbling-blocks
#10
Mohamed B Ezzelarab, Angus W Thomson
The contribution of regulatory T cells (Treg) to the induction and maintenance of tolerance is well-recognized in rodents and may contribute to long-term human organ allograft survival. The therapeutic efficacy of adoptively-transferred Treg in promoting tolerance to organ allografts is well-recognized in mouse models. Early phase 1/2 clinical studies of Treg therapy have been conducted in patients with type-1 (autoimmune) diabetes and refractory Crohn's disease, and for inhibition of graft-versus-host disease following bone marrow transplantation with proven safety...
December 2016: Current Transplantation Reports
https://www.readbyqxmd.com/read/28522594/sphingomyelin-synthase-2-deficiency-inhibits-the-induction-of-murine-colitis-associated-colon-cancer
#11
Toshio Ohnishi, Chieko Hashizume, Makoto Taniguchi, Hidehiro Furumoto, Jia Han, Rongfen Gao, Shinichi Kinami, Takeo Kosaka, Toshiro Okazaki
Sphingomyelin synthase 2 (SMS2) is the synthetic enzyme of sphingomyelin (SM), which regulates membrane fluidity and microdomain structure. SMS2 plays a role in LPS-induced lung injury and inflammation; however, its role in inflammation-mediated tumorigenesis is unclear. We investigated the effect of SMS2 deficiency on dextran sodium sulfate (DSS)-induced murine colitis and found inhibition of DSS-induced inflammation in SMS2-deficient (SMS2(-/-)) mice. DSS treatment induced a significant increase in ceramide levels, with a decrease of SM levels in SMS2(-/-) colon tissue, and demonstrated attenuation of the elevation of both inflammation-related gene expression and proinflammatory cytokines and chemokines, leukocyte infiltration, and MAPK and signal transducer and activator of transcription 3 activation...
May 18, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28521905/harnessing-the-properties-of-dendritic-cells-in-the-pursuit-of-immunological-tolerance
#12
REVIEW
Christopher Horton, Kumaran Shanmugarajah, Paul J Fairchild
The acquisition of self-perpetuating, immunological tolerance specific for graft alloantigens has long been described as the "holy grail" of clinical transplantation. By removing the need for life-long immunosuppression following engraftment, the adverse consequences of immunosuppressive regimens, including chronic infections and malignancy, may be avoided. Furthermore, autoimmune diseases and allergy are, by definition, driven by aberrant immunological responses to ordinarily innocuous antigens. The re-establishment of permanent tolerance towards instigating antigens may, therefore, provide a cure to these common diseases...
April 2017: Biomedical Journal
https://www.readbyqxmd.com/read/28518214/immune-monitoring-as-prerequisite-for-transplantation-tolerance-trials
#13
REVIEW
Katayoun Behnam Sani, Birgit Sawitzki
Ever since its first application in clinical medicine, scientists have urged to induce tolerance towards foreign allogeneic transplants and thus avoid rejection by the recipient's immune system. This would circumvent chronic use of immunosuppressive drugs (IS) and thus avoid development of IS-induced side effects, which are contributing to the still unsatisfactory long-term graft and patient survival after solid organ transplantation. Although manifold strategies of tolerance induction have been described in preclinical models, only three therapeutic approaches have been successfully utilized in a still small number of patients...
May 18, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28518185/osteogenic-potential-of-adipose-derived-macrospheroids-cocultured-with-cd11b-monocytes
#14
Hidemi Nakata, Maiko Yamamoto, Emi Okada, Tomoko Nagayama, Munemitsu Miyasaka, Shohei Kasugai, Shinji Kuroda
PURPOSE: Among potential cell-based therapies, adipose-derived stem cells (ASCs) have been proposed as a promising source of stem cells for tissue regeneration. Although many recent clinical trials have investigated the use of adipose tissue or ASCs in transplantation, analysis of the microstructures of outgrowing macrosized spheroids (macrospheroids) or three-dimensional coculture of ASC spheroids and monocyte/macrophage lineages has not been performed. The aim of this study was to analyze the microstructures of murine-derived ASC macrospheroids and the growth and osteogenic potential of these macrospheroids in a three-dimensional environment and after calcification induction by coculture with monocytes...
May 18, 2017: International Journal of Oral & Maxillofacial Implants
https://www.readbyqxmd.com/read/28515365/ceramide-synthesis-regulates-t-cell-activity-and-gvhd-development
#15
M Hanief Sofi, Jessica Heinrichs, Mohammed Dany, Hung Nguyen, Min Dai, David Bastian, Steven Schutt, Yongxia Wu, Anusara Daenthanasanmak, Salih Gencer, Aleksandra Zivkovic, Zdzislaw Szulc, Holger Stark, Chen Liu, Ying-Jun Chang, Besim Ogretmen, Xue-Zhong Yu
Allogeneic hematopoietic cell transplantation (allo-HCT) is an effective immunotherapy for a variety of hematologic malignances, yet its efficacy is impeded by the development of graft-versus-host disease (GVHD). GVHD is characterized by activation, expansion, cytokine production, and migration of alloreactive donor T cells. Hence, strategies to limit GVHD are highly desirable. Ceramides are known to contribute to inflammation and autoimmunity. However, their involvement in T-cell responses to alloantigens is undefined...
May 18, 2017: JCI Insight
https://www.readbyqxmd.com/read/28514690/genomic-characterization-of-murine-monocytes-reveals-c-ebp%C3%AE-transcription-factor-dependence-of-ly6c-cells
#16
Alexander Mildner, Jörg Schönheit, Amir Giladi, Eyal David, David Lara-Astiaso, Erika Lorenzo-Vivas, Franziska Paul, Louise Chappell-Maor, Josef Priller, Achim Leutz, Ido Amit, Steffen Jung
Monocytes are circulating, short-lived mononuclear phagocytes, which in mice and man comprise two main subpopulations. Murine Ly6C(+) monocytes display developmental plasticity and are recruited to complement tissue-resident macrophages and dendritic cells on demand. Murine vascular Ly6C(-) monocytes patrol the endothelium, act as scavengers, and support vessel wall repair. Here we characterized population and single cell transcriptomes, as well as enhancer and promoter landscapes of the murine monocyte compartment...
May 16, 2017: Immunity
https://www.readbyqxmd.com/read/28512563/acquired-von-willebrand-syndrome-associated-to-secondary-igm-mgus-emerging-after-autologous-stem-cell-transplantation-for-al-amyloidosis
#17
Hina Qamar, Adrienne Lee, Karen Valentine, Leslie Skeith, Victor H Jimenez-Zepeda
Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28511709/incorporation-of-high-dose-131-i-metaiodobenzylguanidine-treatment-into-tandem-high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-high-risk-neuroblastoma-results-of-the-smc-nb-2009-study
#18
Ji Won Lee, Sanghoon Lee, Hee Won Cho, Youngeun Ma, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Eun Joo Cho, Suk-Koo Lee, Do Hoon Lim
BACKGROUND: In our previous SMC NB-2004 study of patients with high-risk neuroblastomas, which incorporated total-body irradiation (TBI) with second high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), the survival rate was encouraging; however, short- and long-term toxicities were significant. In the present SMC NB-2009 study, only TBI was replaced with (131)I-meta-iodobenzylguanidine (MIBG) treatment in order to reduce toxicities. METHODS: From January 2009 to December 2013, 54 consecutive patients were assigned to receive tandem HDCT/auto-SCT after nine cycles of induction chemotherapy...
May 16, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28511345/ros-homeostasis-a-key-determinant-in-liver-ischemic-preconditioning
#19
Ignacio Prieto, María Monsalve
Reactive Oxygen Species (ROS) are key mediators of ischemia-reperfusion injury but also required for the induction of the stress response that limits tissue injury and underlies the protection provided by ischemic-preconditioning protocols. Liver steatosis is an important risk factor for liver transplant failure. Liver steatosis is associated with mitochondrial dysfunction and excessive mitochondrial ROS production. Studies aiming at decreasing the sensibility of the steatotic liver to ischemia-reperfusion injury using pre-conditioning protocols, have shown that the steatotic liver has a reduced capacity to respond to these protocols...
May 4, 2017: Redox Biology
https://www.readbyqxmd.com/read/28510265/severity-and-outcome-of-the-norovirus-infection-in-children-after-intestinal-transplantation
#20
Marie Patte, Danielle Canioni, Véronique Avettand Fenoel, Pierre Frange, Marion Rabant, Cécile Talbotec, Florence Lacaille
In immunocompromised patients, the NoV infection is prolonged and severe. We retrospectively studied the severity of the NoV infection in children after an ITx, the treatment, and the long-term evolution. Norovirus PCR in stools was positive for 19 children in 21 separate episodes. The infection was symptomatic in 18 cases. At diagnosis, the median weight loss was 5% (0-11) and the creatinine clearance was 75 mL/min/1.73 m(2) (19-142). On 14 digestive biopsies, the pathological findings were non-specific with a constant mononuclear infiltration, showing signs of rejection in one case...
May 16, 2017: Pediatric Transplantation
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