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Stem cells transplant

Charlotte V Cox, Paraskevi Diamanti, John P Moppett, Allison Blair
A significant number of children with T-lineage acute lymphoblastic leukemia (T-ALL) fail to respond to therapy and experience early relapse. CD99 has been shown to be overexpressed on T-ALL cells and is considered to be a reliable detector of the disease. However, the relevance of CD99 overexpression in ALL has not been investigated in a functional context. The aim of this study was to investigate the functional capacity of CD99+ cells in childhood ALL and determine the suitability of CD99 as a therapeutic target...
2016: PloS One
Christoph Baldow, Lars Thielecke, Ingmar Glauche
The availability of several methods to unambiguously mark individual cells has strongly fostered the understanding of clonal developments in hematopoiesis and other stem cell driven regenerative tissues. While cellular barcoding is the method of choice for experimental studies, patients that underwent gene therapy carry a unique insertional mark within the transplanted cells originating from the integration of the retroviral vector. Close monitoring of such patients allows accessing their clonal dynamics, however, the early detection of events that predict monoclonal conversion and potentially the onset of leukemia are beneficial for treatment...
2016: PloS One
Hannah K Choe, Usama Gergis, Sebastian A Mayer, Himanshu Nagar, Adrienne A Phillips, Tsiporah B Shore, Michael J Smith, Koen van Besien
BACKGROUND: Preliminary evidence indicates that the addition of low dose TBI (2-4 Gy) to reduced intensity conditioning may reduce the rate of relapse in allogeneic stem cell transplants. In very high risk patients receiving combination haploidentical-single unit cord blood transplants, we have added 4 Gy TBI to the widely used fludarabine, melphalan conditioning regimen, in hopes of reducing relapse and decreasing graft rejection. METHODS: We retrospectively reviewed the posttransplant outcomes of patients who underwent haplo-cord SCT between May 2013 and March 2015 and who received fludarabine 30mg/m2 D-7 to -3, melphalan 140mg/m2 D-2, and 2 Gy TBI D-4 and -3...
October 19, 2016: Transplantation
S Y Zhu, P L Wang, C S Liao, Y Q Yang, C Y Yuan, S Wang, W L Dissanayaka, B C Heng, C F Zhang
BACKGROUND AND OBJECTIVE: The goal of periodontal therapy is to regenerate/reconstruct the damaged supporting tissues of diseased teeth and to facilitate recovery of their physiological functions. Combination of stem cell transplantation and gene therapy offers a viable method for accelerating periodontal repair and regeneration. In this study, the role of the ephrinB2/EphB4 signaling pathway in regulating osteogenic differentiation of periodontal ligament stem cells (PDLSCs) and crosstalk between PDLSCs and pre-osteoblasts within co-culture was investigated through ephrinB2 transgenic expression in PDLSCs...
October 20, 2016: Journal of Periodontal Research
Kipp Weiskopf, Peter J Schnorr, Wendy W Pang, Mark P Chao, Akanksha Chhabra, Jun Seita, Mingye Feng, Irving L Weissman
The hematopoietic stem cell (HSC) is a multipotent stem cell that resides in the bone marrow and has the ability to form all of the cells of the blood and immune system. Since its first purification in 1988, additional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: the myeloid and lymphoid arms. The myeloid arm is characterized by the common myeloid progenitor and all of its resulting cell types...
October 2016: Microbiology Spectrum
Takeshi Kimura, Akihiro Yamashita, Keiichi Ozono, Noriyuki Tsumaki
Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors...
October 20, 2016: Tissue Engineering. Part A
Qingxi Zhang, Wanling Chen, Sheng Tan, Tongxiang Lin
Parkinson's disease (PD) is the second most frequent neurodegenerative disease after Alzheimer's disease, which is characterized by low level of dopamine expressing in the striatum and deteriorated dopaminergic neurons (DAn) in Substantia nigra pars compacta (SNpc). Generation of PD-derived DAn including differentiation of human embryonic stem cell (hESC), human neural stem cell (hNSC), human induced pluripotent stem cell (hiPSC) and directly reprogramming provide an ideal tool to model PD, which created the possibilities of mimicking key essential pathological processes charactering single cell changes in vitro...
October 20, 2016: Human Gene Therapy
Animesh Pardanani
: Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant...
November 2016: American Journal of Hematology
Jennifer E Adair, Timothy Waters, Kevin G Haworth, Sara P Kubek, Grant D Trobridge, Jonah D Hocum, Shelly Heimfeld, Hans-Peter Kiem
Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34(+) blood cell products for transplantation...
October 20, 2016: Nature Communications
B P C Hoppe, E de Jongh, A Griffioen-Keijzer, J M Zijlstra-Baalbergen, E P F IJzerman, F Baboe
Human metapneumovirus (hMPV) is a paramyxovirus that causes respiratory tract infections ranging from mild upper airway infection to severe pneumonia. Patients with haematological disease, especially haematopoietic stem cell transplantation (HSCT) recipients, are more likely to develop more severe infections. We describe three cases of hMPV infection in HSCT patients. The most reliable diagnostic procedure for hMPV is multiplex ligation-dependent probe amplification (MLPA) on a nasopharyngeal swab. Sensitivity and specificity of MLPA to detect hMPV is high and time to diagnosis is short...
October 2016: Netherlands Journal of Medicine
Vignesh Kandakumar, Vishnu Nagalapuram, Sujaya Menon
Light chain deposition disease (LCDD) is a rare systemic disorder in which monoclonal light chains are abnormally secreted due to clonal proliferation of plasma cells and get deposited in various organs; the kidneys being the common one to be affected leading to renal failure. Advocated therapeutic options include chemotherapy with alkylating agents and steroids, High-Dose Melphalan (HDM) with Autologous Stem Cell Transplantation. Recently, Bortezomib has proven to be a novel therapeutic option in these patients when combined with dexamethasone...
August 2016: Journal of the Association of Physicians of India
Nirali N Shah, Theresa M Watson, Bonnie Yates, David J Liewehr, Seth M Steinberg, David Jacobsohn, Terry J Fry
BACKGROUND: Diagnosis of engraftment syndrome (ES) following allogeneic hematopoietic stem cell transplantation (HSCT) can be a challenge due to the systemic presentation and alternative etiologies. With a goal of establishing biomarkers to more accurately distinguish ES, we prospectively analyzed levels of cytokines during HSCT. PROCEDURES: We performed a prospective study of children ≤21 years who underwent allogeneic HSCT. Blood samples for interleukin (IL)-6, IL-8, IL-10, IL-1b, IL-12p70, interferon-γ, tumor necrosis factor alpha (TNF-α) and procalcitonin were obtained from each subject prior to conditioning, at day 0, and then biweekly through engraftment and at days 30, 60 and 100...
October 20, 2016: Pediatric Blood & Cancer
J Wu, A Platero Luengo, M A Gil, K Suzuki, C Cuello, M Morales Valencia, I Parrilla, C A Martinez, A Nohalez, J Roca, E A Martinez, J C Izpisua Belmonte
More than eighteen years have passed since the first derivation of human embryonic stem cells (ESCs), but their clinical use is still met with several challenges, such as ethical concerns regarding the need of human embryos, tissue rejection after transplantation and tumour formation. The generation of human induced pluripotent stem cells (iPSCs) enables the access to patient-derived pluripotent stem cells (PSCs) and opens the door for personalized medicine as tissues/organs can potentially be generated from the same genetic background as the patient recipients, thus avoiding immune rejections or complication of immunosuppression strategies...
October 2016: Reproduction in Domestic Animals, Zuchthygiene
Katsuto Takenaka, Kazuya Shimoda, Naoyuki Uchida, Taizo Shimomura, Koji Nagafuji, Tadakazu Kondo, Hirohiko Shibayama, Takehiko Mori, Kensuke Usuki, Taichi Azuma, Yutaka Tsutsumi, Junji Tanaka, Hitomi Dairaku, Keitaro Matsuo, Keiya Ozawa, Mineo Kurokawa, Shunya Arai, Koichi Akashi
We conducted a 17-year nationwide survey (1999-2015) to elucidate the clinical outcomes of patients with primary myelofibrosis (PMF) in Japan. Questionnaires were sent annually to approximately 500 hematology departments. Newly diagnosed patients with PMF were enrolled in this study, and were followed up annually to collect prognostic information. Approximately 50 patients were enrolled per year, yielding a total of 780 patients with PMF included in this study. The median age at diagnosis was 66 years. At the time of analysis, the median survival duration was 47 months, and the 3-year overall survival rate was 59 %...
October 19, 2016: International Journal of Hematology
Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Hidekazu Nishikii, Byung-Su Kim, Yasuhisa Yokoyama, Yan Chen, Jeanette Baker, Antonio Pierini, Maite Alvarez, Melissa Mavers, Kristina Maas-Bauer, Yuqiong Pan, Shigeru Chiba, Robert S Negrin
CD4(+)Foxp3(+) regulatory T cells (Treg) are a subpopulation of T cells, which regulate the immune system and enhance immune tolerance after transplantation. Donor-derived Treg prevent the development of lethal acute graft versus host disease (GVHD) in murine models of allogeneic hematopoietic stem cell transplantation (HCT). We recently demonstrated that a single treatment of the agonistic antibody to DR3 (Death receptor 3, αDR3) to donor mice resulted in the expansion of donor derived Treg and prevented acute GVHD, although the precise role of DR3 signaling in GVHD has not been elucidated...
October 19, 2016: Blood
Omar S Aljitawi, Soumen Paul, Avishek Ganguly, Tara L Lin, Sid Ganguly, George Vielhauer, Maegan L Capitano, Amy Cantelina, Brea Lipe, Jonathan D Mahnken, Amanda Wise, Abigale Berry, Anurag K Singh, Leyla Shune, Christopher Lominska, Sunil Abhyankar, Dennis Allin, Mary Laughlin, Joseph P McGuirk, Hal E Broxmeyer
Umbilical cord blood (UCB) engraftment is in part limited by graft cell dose, generally one log less than that of bone marrow (BM)/peripheral blood (PB) cell grafts. Strategies toward increasing hematopoietic stem/progenitor cell (HSPC) homing to BM have been assessed in order to improve UCB engraftment. Despite recent progress, a complete understanding of how HSPC homing and engraftment are regulated is still elusive. We provide evidence that blocking erythropoietin (EPO)-EPO receptor (R) signaling promotes homing to BM and early engraftment of UCB CD34(+) cells...
October 19, 2016: Blood
B S Wang, H Y Yang, Y Han
Objective: To determine the effects of adipose-derived stem cells (ADSCs) on the survival rate of flaps by transplanting ADSCs into the experimental flaps pre-operatively. Methods: ADSCs were isolated from fresh human fat and cultured in vitro. Their morphological characters were observed, and flowcytometry and differentiation test and evaluation were conducted. A total of 40 BALB/c mice were divided into 5 groups randomly with each of 8 mice. 1 cm×4 cm random skin flap was designed on the mice back, ADSCs were injected in advance into subcutaneous tissues of 3 groups, the operation was performed on the 2(nd,) 5(th) and 7(th) day after the ADSCs injection, meanwhile skin flap operation was conducted in the immediate injection group and control group...
September 27, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Himalee S Sabnis, Heath L Bradley, Shweta Tripathi, Wen-Mei Yu, William Tse, Cheng-Kui Qu, Kevin D Bunting
Current therapy for acute myeloid leukemia (AML) primarily includes high-dose cytotoxic chemotherapy with or without allogeneic stem cell transplantation. Targeting unique cellular metabolism of cancer cells is a potentially less toxic approach. Monotherapy with mitochondrial inhibitors like metformin have met with limited success since escape mechanisms such as increased glycolytic ATP production, especially in hyperglycemia, can overcome the metabolic blockade. As an alternative strategy for metformin therapy, we hypothesized that the combination of 6-benzylthioinosine (6-BT), a broad-spectrum metabolic inhibitor, and metformin could block this drug resistance mechanism...
October 5, 2016: Leukemia Research
Tom Bongiorno, Jena L Chojnowski, James D Lauderdale, Todd Sulchek
Healthy eyes contain a population of limbal stem cells (LSCs) that continuously renew the corneal epithelium. However, each year, 1 million Americans are afflicted with severely reduced visual acuity caused by corneal damage or disease, including LSC deficiency (LSCD). Recent advances in corneal transplant technology promise to repair the cornea by implanting healthy LSCs to encourage regeneration; however, success is limited to transplanted tissues that contain a sufficiently high percentage of LSCs. Attempts to screen limbal tissues for suitable implants using molecular stemness markers are confounded by the poorly understood signature of the LSC phenotype...
October 18, 2016: Biophysical Journal
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