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T-cells, bone marrow transplant

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https://www.readbyqxmd.com/read/28319565/bone-marrow-graft-versus-host-disease-in-major-histocompatibility-complex-matched-murine-reduced-intensity-allogeneic-hemopoietic-cell-transplantation
#1
Kifah Shahin, Zamil Mattar, Pablo Silveira, Wei-Hsun Hsu, Linda Bendall, Derek Hart, Kenneth F Bradstock
BACKGROUND: Most clinical allogeneic hemopoietic cell transplants (alloHCT) are now performed using reduced intensity conditioning (RIC) instead of myeloablative (MAC) conditioning, however, the biology underlying this treatment remains incompletely understood. METHODS: We investigated a murine model of major histocompatibility complex (MHC)-matched multiple minor histocompatibility antigen mismatched alloHCT, using bone marrow (BM) cells and splenocytes from B6 (H-2) donor mice transplanted into BALB...
March 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28319080/adverse-impact-of-high-donor-cd3-cell-dose-on-outcome-following-tandem-auto-nma-allogeneic-transplantation-for-high-risk-myeloma
#2
A P Nair, P Walker, A Kalff, K Bergin, J Hocking, S Avery, D J Curtis, S Patil, T Das, D Klarica, S Morgan, J Muirhead, M Gorniak, J Reynolds, A Spencer
High-risk (HR) multiple myeloma (MM) has poor outcomes with conventional therapy. Tandem autologous-non-myeloablative (NMA) allogeneic stem cell transplantation (autologous stem cell transplantation (ASCT)-NMA allogeneic SCT) is potentially curative secondary to graft-versus-myeloma effect. We retrospectively analysed ASCT-NMA allogeneic SCT outcomes of 59 HR and relapsed MM patients. At a median follow-up of 35.8 months, the outcomes for HR-MM upfront tandem ASCT-NMA allogeneic SCT and standard-risk (SR) MM upfront ASCT alone were comparable (median PFS 1166 days versus 1465 days, P=0...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319076/clinical-impact-of-hyperglycemia-on-days-0-7-after-allogeneic-stem-cell-transplantation
#3
A Kawajiri, S Fuji, Y Tanaka, C Kono, T Hirakawa, T Tanaka, R Ito, Y Inoue, K Okinaka, S Kurosawa, Y Inamoto, S-W Kim, T Yamashita, T Fukuda
In order to clarify the association between hyperglycemia during the early period after allogeneic stem cell transplantation (allo-SCT) and adverse outcomes, we retrospectively analyzed 563 consecutive patients who underwent allo-SCT at our institute between 2008 and 2015. Patients were categorized into three groups according to mean fasting blood glucose levels on days 0-7 (normoglycemia group<110 mg/dL, n=347; mild hyperglycemia group 110-149 mg/dL, n=192 and moderate/severe hyperglycemia group≥150 mg/dL, n=24)...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319074/tregs-hype-or-hope-for-allogeneic-hematopoietic-stem-cell-transplantation
#4
REVIEW
F Lussana, M Di Ianni, A Rambaldi
The discovery of T regulatory cells has been one of the most important advances in basic immunology and has opened the door to the development of innovative therapeutic strategies for improving the outcome of solid organ and hematopoietic stem cell transplantation. Basic immunology is rapidly elucidating the complex biology of these cells even though the difficulties in purifying or even expanding them in vitro represent a major limitation to the development of clinical studies. The clinical benefit potentially associated with this therapeutic approach remains to be demonstrated...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319073/ex-vivo-t-cell-depletion-in-allogeneic-hematopoietic-stem-cell-transplant-past-present-and-future
#5
REVIEW
A Saad, L S Lamb
The most common cause of post-transplant mortality in patients with hematological malignancy is relapse, followed by GvHD, infections, organ toxicity and second malignancy. Immune-mediated complications such as GvHD continue to be challenging, yet amenable to control through manipulation of the T-cell compartment of the donor graft with subsequent immunomodulation after transplant. However, risk of both relapse and infection increase concomitantly with T-cell depletion (TCD) strategies that impair immune recovery...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319072/long-term-follow-up-of-a-retrospective-comparison-of-reduced-intensity-conditioning-and-conventional-high-dose-conditioning-for-allogeneic-transplantation-from-matched-related-donors-in-myelodysplastic-syndromes
#6
R Martino, A Henseler, M van Lint, N Schaap, J Finke, D Beelen, S Vigouroux, E P Alessandrino, G J Mufti, J H Veelken, B Bruno, I Yakoub-Agha, L Volin, J Maertens, R Or, V Leblond, M Rovira, P Kalhs, A F Alvarez, A Vitek, J Sierra, E Wagner, M Robin, T de Witte, N Kröger
This study shows the long-term updated outcomes of a multicenter retrospective study which analyzed 843 patients with myelodysplastic syndrome (MDS) who underwent transplantation with an HLA-identical sibling donor with either reduced-intensity conditioning (RIC) in 213 patients, or standard myeloablative conditioning (MAC) in 630 patients. In multivariate analysis, the 13-year relapse rate was significantly increased after RIC (31% after MAC vs 48% in RIC; HR, 1.5; 95% CI, 1.1-1.9; P=0.04), but with no differences in overall survival (OS) (30% after MAC vs 27% in RIC; P=0...
March 20, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28319044/fibroblastic-niches-prime-t-cell-alloimmunity-through-delta-like-notch-ligands
#7
Jooho Chung, Christen L Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R Blazar, Alex Y Huang, Todd V Brennan, D Keith Bishop, Burkhard Ludewig, Christian W Siebel, Freddy Radtke, Sanjiv A Luther, Ivan Maillard
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318017/thymic-crosstalk-restrains-the-pool-of-cortical-thymic-epithelial-cells-with-progenitor-properties
#8
Catarina Meireles, Ana R Ribeiro, Rute D Pinto, Catarina Leitão, Pedro M Rodrigues, Nuno L Alves
Cortical (cTEC) and medullary (mTEC) thymic epithelial cells establish key microenvironments for T-cell differentiation and arise from thymic epithelial cell progenitors (TEP). However, the nature of TEPs and the mechanism controlling their stemness in the postnatal thymus remain poorly defined. Using TEC clonogenic assays as a surrogate to survey TEP activity, we found that a fraction of cTECs generates specialized clonal-derived colonies, which contain cells with sustained colony-forming capacity (ClonoTECs)...
March 20, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28302713/family-cord-blood-banking-for-sickle-cell-disease-a-twenty-year-experience-in-two-dedicated-public-cord-blood-banks
#9
Hanadi Rafii, Françoise Bernaudin, Helene Rouard, Valérie Vanneaux, Annalisa Ruggeri, Marina Cavazzana, Valerie Gauthereau, Aurélie Stanislas, Malika Benkerrou, Mariane De Montalembert, Christele Ferry, Robert Girot, Cecile Arnaud, Annie Kamdem, Joelle Gour, Claudine Touboul, Audrey Cras, Mathieu Kuentz, Claire Rieux, Fernanda Volt, Barbara Cappelli, Karina T Maio, Annalisa Paviglianiti, Chantal Kenzey, Jerome Larghero, Eliane Gluckman
Efforts to implement family cord blood banking have been developed in the past decades for siblings requiring stem cell transplantation for conditions such as sickle cell disease. However, public banks are faced with challenging decisions about the units to be stored, discarded, or used for other endeavors. We report here 20 years of experience in family cord blood banking for sickle cell disease in two dedicated public banks. Participants were pregnant women who had previous child diagnosed with homozygous sickle cell disease...
March 16, 2017: Haematologica
https://www.readbyqxmd.com/read/28297581/systemic-delivery-of-bone-marrow-mesenchymal-stem-cells-for-in-situ-intervertebral-disc-regeneration
#10
Carla Cunha, Catarina R Almeida, Maria Inês Almeida, Andreia M Silva, Maria Molinos, Sofia Lamas, Catarina L Pereira, Graciosa Q Teixeira, António T Monteiro, Susana G Santos, Raquel M Gonçalves, Mário A Barbosa
Cell therapies for intervertebral disc (IVD) regeneration presently rely on transplantation of IVD cells or stem cells directly to the lesion site. Still, the harsh IVD environment, with low irrigation and high mechanical stress, challenges cell administration and survival. In this study, we addressed systemic transplantation of allogeneic bone marrow mesenchymal stem cells (MSCs) intravenously into a rat IVD lesion model, exploring tissue regeneration via cell signaling to the lesion site. MSC transplantation was performed 24 hours after injury, in parallel with dermal fibroblasts as a control; 2 weeks after transplantation, animals were killed...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28296231/high-resolution-hla-a-b-and-drb1-allele-and-haplotype-frequencies-in-7823-han-marrow-donors-of-liaoning-province-china
#11
L-N Shao, S-T Zhang, W-J Yu, S-H Zhou, Y Duan, L-Z Pan, N Wang, M Liu
BACKGROUND: The human leukocyte antigen (HLA) system is the most polymorphic gene cluster in humans. High-resolution donor-recipient matching for HLA genes improves patient survival after unrelated hematopoietic stem cell transplantation. MATERIALS AND METHODS: In this study, we analyzed the high-resolution allele and haplotype frequencies at the HLA-A, -B and -DRB1 loci in the Liaoning Han population and analyzed its relationships with other populations. RESULTS: The 3 most frequent alleles at the HLA-A, -B and -DRB1 loci were A*24:02, A*02:01:01G, A*11:01; B*13:02, B*46:01, B*40:01:01G; DRB1*09:01, DRB1*15:01 and DRB1*07:01, respectively...
March 12, 2017: HLA
https://www.readbyqxmd.com/read/28295901/high-aldehyde-dehydrogenase-activity-identifies-a-subset-of-human-mesenchymal-stromal-cells-with-vascular-regenerative-potential
#12
Stephen E Sherman, Miljan Kuljanin, Tyler T Cooper, David M Putman, Gilles A Lajoie, David A Hess
During culture expansion, multipotent mesenchymal stromal cells (MSC) differentially express aldehyde dehydrogenase (ALDH), an intracellular detoxification enzyme that protects long-lived cells against oxidative stress. Thus, MSC selection based on ALDH-activity may be used to reduce heterogeneity and distinguish MSC subsets with improved regenerative potency. After expansion of human bone marrow-derived MSC, cell progeny were purified based on low versus high ALDH-activity by fluorescence activated cell sorting, and each subset was compared for multipotent stromal and pro-vascular regenerative functions...
March 15, 2017: Stem Cells
https://www.readbyqxmd.com/read/28292332/aberrant-t-cell-responses-in-the-bone-marrow-microenvironment-of-patients-with-poor-graft-function-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
Yuan Kong, Yu-Tong Wang, Xie-Na Cao, Yang Song, Yu-Hong Chen, Yu-Qian Sun, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang
BACKGROUND: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Nevertheless, whether abnormalities of T cell subsets in the bone marrow (BM) immune microenvironment, including Th17, Tc17, Th1, Tc1, Th2, Tc2 cells and regulatory T cells (Tregs), are involved in the pathogenesis of PGF remains unclear. METHODS: This prospective nested case-control study enrolled 20 patients with PGF, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD)...
March 14, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28289507/impact-of-t-cells-on-hematopoietic-stem-and-progenitor-cell-function-good-guys-or-bad-guys
#14
REVIEW
Sulima Geerman, Martijn A Nolte
When hematopoietic stem and progenitor cells (HSPC) are harvested for transplantation, either from the bone marrow or from mobilized blood, the graft contains a significant number of T cells. It is these T cells that are the major drivers of graft-vs-host disease (GvHD). The risk for GvHD can simply be reduced by the removal of these T cells from the graft. However, this is not always desirable, as this procedure also decreases the engraftment of the transplanted HSPCs and, if applicable, a graft-vs-tumor effect...
February 26, 2017: World Journal of Stem Cells
https://www.readbyqxmd.com/read/28287644/mesenchymal-stromal-cell-infusion-to-treat-steroid-refractory-acute-gvhd-iii-iv-after-hematopoietic-stem-cell-transplantation
#15
G M Dotoli, G C De Santis, M D Orellana, K de Lima Prata, S R Caruso, T R Fernandes, V A Rensi Colturato, A T Kondo, N Hamerschlak, B P Simões, D T Covas
Acute GvHD (aGvHD) is a life-threatening complication of hematopoietic stem cell transplantation. Frontline therapy for aGvHD consists of corticosteroid administration. However, ∼25% of the patients have a steroid-refractory disease, a sign of poor prognosis. An alternative therapy for steroid-refractory aGvHD is infusion of mesenchymal stromal cells (MSCs). Herein, we report the results of 46 patients treated with MSC infusion as salvage therapy for steroid-refractory aGvHD III/IV (78% grade IV). Patients received a median cumulative dose of MSCs of 6...
March 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28287638/state-of-the-art-fertility-preservation-in-children-and-adolescents-undergoing-haematopoietic-stem-cell-transplantation-a-report-on-the-expert-meeting-of-the-paediatric-diseases-working-party-pdwp-of-the-european-society-for-blood-and-marrow-transplantation
#16
J-H Dalle, G Lucchini, A Balduzzi, M Ifversen, K Jahnukainen, K T Macklon, A Ahler, A Jarisch, M Ansari, E Beohou, D Bresters, S Corbacioglu, A Dalissier, C Diaz de Heredia Rubio, T Diesch, B Gibson, T Klingebiel, A Lankester, A Lawitschka, R Moffat, C Peters, C Poirot, N Saenger, P Sedlacek, E Trigoso, K Vettenranta, J Wachowiak, A Willasch, M von Wolff, I Yaniv, A Yesilipek, P Bader
Nowadays, allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a well-established treatment procedure and often the only cure for many patients with malignant and non-malignant diseases. Decrease in short-term complications has substantially contributed to increased survival. Therefore long-term sequelae are reaching the focus of patient care. One of the most important risks of stem cell transplant survivors is infertility. As well as in the field of allo-HSCT also the field of reproductive medicine has achieved substantial advances to offer potential options for fertility preservation in both boys and girls...
March 13, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28286199/abnormalities-of-the-bone-marrow-immune-microenvironment-in-patients-with-prolonged-isolated-thrombocytopenia-after-allogeneic-hematopoietic-stem-cell-transplantation
#17
Yang Song, Min-Min Shi, Yuan-Yuan Zhang, Xiao-Dong Mo, Yu Wang, Xiao-Hui Zhang, Lan-Ping Xu, Xiao-Jun Huang, Yuan Kong
Prolonged isolated thrombocytopenia (PT) is a serious complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, whether abnormalities of the bone marrow immune microenvironment are involved in the pathogenesis of PT remains unknown. In total, 20 patients with PT, 40 matched patients with good graft function (GGF) after allo-HSCT, and 20 healthy donors (HD) were enrolled in this nested case-control study. Th1, Th2, Tc1, Tc2, Th17 and Treg cells were analysed by flow cytometry, and IFN-γ, IL-4, IL-17, IL-6, IL-21 and thrombopoietin levels in bone marrow (BM) plasma were evaluated using cytometric beads assay and enzyme-linked immunosorbent assay...
March 9, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28281429/single-centre-experience-of-allogeneic-haemopoietic-stem-cell-transplant-in-paediatric-patients-in-cape-town-south-africa
#18
A Van Eyssen, N Novitsky, P De Wit, T Schlaphoff, V Thomas, D Pillay, M Hendricks, A Davidson
BACKGROUND: Allogeneic haemopoietic stem cell transplant (Allo-HSCT) is a specialised and costly intervention, associated with significant morbidity and mortality. It is used to treat a broad range of paediatric conditions. South Africa (SA) is an upper middle-income country with limitations on healthcare spending. The role of paediatric Allo-HSCT in this setting is reviewed. OBJECTIVES: To review paediatric patients who underwent Allo-HSCT at the Groote Schuur Hospital/University of Cape Town Private Academic Hospital transplant unit in Cape Town, South Africa, and received post-transplant care at Red Cross War Memorial Children's Hospital, over the period January 2006 - December 2014 in respect of indications for the transplant, donor sources, conditioning regimens, treatment-related morbidity and overall survival (OS)...
February 27, 2017: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/28275010/epithelial-and-non-epithelial-patched-1-ptch1-play-opposing-roles-to-regulate-proliferation-and-morphogenesis-of-the-mouse-mammary-gland
#19
Teresa Monkkonen, John D Landua, Adriana P Visbal, Michael T Lewis
Patched-1 (Ptch1) has epithelial, stromal, and systemic roles in murine mammary gland organogenesis, yet specific functions remain undefined. Cre-recombinase-mediated Ptch1 ablation in mammary epithelium increased proliferation and branching, but did not phenocopy transgenic expression of activated Smoothened (SmoM2). Epithelium showed no evidence of canonical hedgehog signaling, and hyperproliferation was not blocked by SMO inhibition, suggesting a non-canonical function of PTCH1. Consistent with this possibility, nuclear localization of Cyclin B1 was increased...
March 8, 2017: Development
https://www.readbyqxmd.com/read/28273362/tlr5-signaling-restrains-t-nkt-cell-activation-and-protects-against-concanavalin-a-induced-hepatic-injury
#20
Lei Wang, Wen Zhang, Chang-Hui Ge, Rong-Hua Yin, Xiao Yang, Yi-Qun Zhan, Miao Yu, Chang-Yan Li, Zhi-Qiang Ge, Xiao-Ming Yang
TLR5 signaling regulates the immune privileged status of the liver and is involved in hepatic immune disorders. However, the role of TLR5 has not yet been investigated in experimental models of Con A-mediated liver injury. Here, we show that TLR5 is highly upregulated in the hepatic mononuclear cells (MNCs) of mice during Con A-induced hepatitis. Increased mortality and liver histopathology of TLR5-deficient mice correlated with excessive production of pro-inflammatory cytokines, suggesting that TLR5 knockout mice were more susceptible to Con A-induced hepatitis...
March 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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