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Nathan Punwani, Noah Merin, Ann Mohrbacher, George Yaghmour, Allison Sano, Laleh Ramezani, Preet M Chaudhary, Giridharan Ramsingh
Microtransplantation (MST), a type of HLA-mismatched allogeneic cellular therapy, is a promising, cellular therapy for acute myeloid leukemia (AML). MST transfuses granulocyte colony-stimulating factor (G-CSF)-mobilized, HLA-mismatched donor peripheral blood stem cells into patients undergoing conventional chemotherapy. MST, using haploidentical donors, has been shown to yield clinical benefit without any permanent marrow engraftment in AML. Consequently, graft-versus-host disease concerns are rendered irrelevant with no need for immunosuppression...
2018: Leukemia Research Reports
Li Wang, Fan Du, Hongxiang Wang, Conghua Xie
Previous studies have demonstrated that infusion of allogeneic matched and haploidentical peripheral blood stem cells with minimal conditioning (microtransplantation) achieved durable responses in patients with refractory leukemia/lymphoma in the absence of engraftment. The mechanisms underlying this response have not been thoroughly elucidated, while host-versus-graft reactions are likely to have an important role. The present study established a mismatched microtransplantation mouse model of leukemia to study the roles of CD4+ T cells and CD8+ T cells in changes of interferon (IFN)-γ and interleukin (IL)-4 release to explore the mechanisms of the effects of microtransplantation...
February 2018: Experimental and Therapeutic Medicine
David Kliman, Gloria Castellano-Gonzalez, Barbara Withers, Janine Street, Elizabeth Tegg, Oksana Mirochnik, Joey Lai, Leighton Clancy, David Gottlieb, Emily Blyth
Current techniques to assess chimerism after hematopoietic stem cell transplantation (HSCT) are limited in both sensitivity and precision. These drawbacks are problematic in the context of cellular therapies that frequently result in microchimerism (donor chimerism <1%). We have developed a highly sensitive droplet digital PCR (ddPCR) assay using commercially available regents with good performance throughout the range of clinically relevant chimerism measurements, including microchimerism. We tested the assay using spiked samples of known donor-recipient ratios and in clinical samples from HSCT recipients and patients enrolled on clinical trials of microtransplantation and third-party virus-specific T cells (VSTs)...
January 2, 2018: Biology of Blood and Marrow Transplantation
Mei Guo, Nelson J Chao, Jian-Yong Li, David A Rizzieri, Qi-Yun Sun, Ann Mohrbacher, Elizabeth F Krakow, Wan-Jun Sun, Xu-Liang Shen, Xin-Rong Zhan, De-Pei Wu, Li Liu, Juan Wang, Min Zhou, Lin-Hua Yang, Yang-Yi Bao, Zheng Dong, Bo Cai, Kai-Xun Hu, Chang-Lin Yu, Jian-Hui Qiao, Hong-Li Zuo, Ya-Jing Huang, Anthony D Sung, Jun-Xiao Qiao, Zhi-Qing Liu, Tie-Qiang Liu, Bo Yao, Hong-Xia Zhao, Si-Xuan Qian, Wei-Wei Liu, Rafael Forés, Rafael F Duarte, Hui-Sheng Ai
Importance: The outcome of older patients with acute myeloid leukemia (AML) remains unsatisfactory. Recent studies have shown that HLA-mismatched microtransplant could improve outcomes in such patients. Objective: To evaluate outcomes in different age groups among older patients with newly diagnosed AML who receive HLA-mismatched microtransplant. Design, Setting, and Participants: This multicenter clinical study included 185 patients with de novo AML at 12 centers in China, the United States, and Spain in the Microtransplantation Interest Group...
January 1, 2018: JAMA Oncology
Wen Shen, Changlong Nan, Peter T Nelson, Harris Ripps, Malcolm M Slaughter
Ionotropic receptors are tightly regulated by second messenger systems and are often present along with their metabotropic counterparts on a neuron's plasma membrane. This leads to the hypothesis that the two receptor subtypes can interact, and indeed this has been observed in excitatory glutamate and inhibitory GABA receptors. In both systems the metabotropic pathway augments the ionotropic receptor response. However, we have found that the metabotropic GABAB receptor can suppress the ionotropic GABAA receptor current, in both the in vitro mouse retina and in human amygdala membrane fractions...
March 2017: Physiological Reports
Kevin A David, Dennis Cooper, Roger Strair
The anti-tumor effects of allogeneic hematopoietic stem cell transplantation depend upon engraftment of donor cells followed by a graft-versus-tumor (GVT) effect. However, pre-clinical and clinical studies have established that under certain circumstances, anti-tumor responses can occur despite the absence of high levels of durable donor cell engraftment. Tumor response with little or no donor engraftment has been termed "microtransplantation." It has been hard to define conditions leading to tumor responses without donor cell persistence in humans because the degree of engraftment depends very heavily upon many patient-specific factors, including immune status and degree of prior therapy...
February 2017: Current Hematologic Malignancy Reports
L Qian, J Shen
No abstract text is available yet for this article.
November 24, 2015: West Indian Medical Journal
Gabriele Ruffolo, Anand Iyer, Pierangelo Cifelli, Cristina Roseti, Angelika Mühlebner, Jackelien van Scheppingen, Theresa Scholl, Johannes A Hainfellner, Martha Feucht, Pavel Krsek, Josef Zamecnik, Floor E Jansen, Wim G M Spliet, Cristina Limatola, Eleonora Aronica, Eleonora Palma
Tuberous sclerosis complex (TSC) is a rare multi-system genetic disease characterized by several neurological disorders, the most common of which is the refractory epilepsy caused by highly epileptogenic cortical lesions. Previous studies suggest an alteration of GABAergic and glutamatergic transmission in TSC brain indicating an unbalance of excitation/inhibition that can explain, at least in part, the high incidence of epilepsy in these patients. Here we investigate whether TSC cortical tissues could retain GABAA and AMPA receptors at early stages of human brain development thus contributing to the generation and recurrence of seizures...
November 2016: Neurobiology of Disease
Weiye Nie, Qin Huang, Yongsheng Chen, Xiaolin Yin
Invasive aspergillosis infection (IF) in patients with hematologic malignancies is common. Prognosis of IF in patients with acute myeloid leukemia (AML) not responsive to chemotherapy is very poor, especially when neutropenia is duration. Fractional HLA haplo-identical mobilized neutropenia peripheral blood stem cell (PBSC) transfusion, which was defined as micro-transplantation, was recently adopted in treatment of elder patients with AML and shown to be effective in fasting hemopoiesis recovery. Here we report the outcome of an elderly patient with AML accompanying IF treated with microtransplantation and voriconazole...
June 2016: Indian Journal of Hematology & Blood Transfusion
Edwin Murenzi, Abigail C Toltin, Steven B Symington, Molly M Morgan, John M Clark
Microtransplantation of mammalian brain neurolemma into the plasma membrane of Xenopus oocytes is used to study ion channels in their native form as they appear in the central nervous system. Use of microtransplanted neurolemma is advantageous for various reasons: tissue can be obtained from various sources and at different developmental stages; ion channels and receptors are present in their native configuration in their proper lipid environment along with appropriate auxiliary subunits; allowing the evaluation of numerous channelpathies caused by neurotoxicants in an ex vivo state...
April 7, 2016: Neurotoxicology
Kai-Xun Hu, Qi-Yun Sun, Mei Guo, Jun-Xiao Qiao, Chang-Lin Yu, Jian-Hui Qiao, Zheng Dong, Wan-Jun Sun, Hong-Li Zuo, Ya-Jing Huang, Bo Cai, Hui-Sheng Ai
UNLABELLED: The treatment outcomes of myelodysplastic syndrome (MDS) and transformed acute myelogenous leukemia (tAML) remain very unsatisfactory. We designed a combination of human leukocyte antigen (HLA)-mismatched hematopoietic stem cell microtransplantation (MST) with chemotherapy for patients with MDS and tAML and evaluated its effects and toxicity. Patients were between 13 and 79 years old. Patients with MDS (n=21) were given HLA-mismatched MST combined with decitabine and cytarabine; patients with tAML (n=22) were given HLA-mismatched MST combined with decitabine and cytarabine, and also mitoxantrone...
April 2016: Stem Cells Translational Medicine
Hong Tian, Qi Qu, Liming Liu, Depei Wu
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most effective post remission treatment for leukemia, resulting in lower relapse rates than alternative therapies. However, it is limited by the lack of suitable human leukocyte antigen (HLA) matched donors and high rates of transplant-related morbidity and mortality. Cord blood transplantation (CBT) and haploidentical SCT (haplo-SCT) expand the potential donor pool but are also associated with major complications. Co-infusion of third-party donor stem cells with a CBT/haplo-SCT, which is called "dual transplantation," has been reported to improve the outcome of HSCT by accelerating hematopoietic reconstitution and reducing the incidence of graft-versus-host disease (GVHD)...
2016: Current Stem Cell Research & Therapy
Cristina Roseti, Erwin A van Vliet, Pierangelo Cifelli, Gabriele Ruffolo, Johannes C Baayen, Maria Amalia Di Castro, Cristina Bertollini, Cristina Limatola, Eleonora Aronica, Annamaria Vezzani, Eleonora Palma
Temporal lobe epilepsy (TLE) is the most prevalent form of adult focal onset epilepsy often associated with drug-resistant seizures. Numerous studies suggest that neuroinflammatory processes are pathologic hallmarks of both experimental and human epilepsy. In particular, the interleukin (IL)-1β/IL-1 receptor type 1 (R1) axis is activated in epileptogenic tissue, where it contributes significantly to the generation and recurrence of seizures in animal models. In this study, we investigated whether IL-1β affects the GABA-evoked currents (I(GABA)) in TLE tissue from humans...
October 2015: Neurobiology of Disease
Xiangjing Kong, Yongsheng Chen, L I Wang, Yali Zhou, Yuanyuan He, Weiye Nie, Xinhua Zhang, Xiaolin Yin
The incidence of acute myeloid leukemia (AML) increases with age. Elderly patients with AML are less tolerant to high-intensity consolidation therapy than younger patients, with significantly worse prognoses. Induction and consolidation therapy combined with allogeneic hematopoietic stem cell microtransplantation may improve the prognosis of elderly patients with AML. The present study reports the effect of maintenance therapy with low-dose chemotherapy treatment combined with microtransplantation in elderly patients with AML following consolidation...
May 2015: Oncology Letters
Ying-Jun Chang, Yu Wang, Xiao-Jun Huang
Haploidentical stem cell transplantation (haplo-SCT), either with T-cell depletion or T-cell replete, has been a reliable source of stem cells for patients with high-risk leukemia who do not have matched donors because it provides comparable outcomes to human leukocyte antigen-matched sibling donor transplantation, unrelated donor transplantation and umbilical cord blood transplantation. Factors, such as the Hematopoietic Cell Transplantation-Specific Comorbidity Index, associated with transplant outcomes may help us design risk-stratification-directed intervention to improve the prognosis of leukemia patients...
October 2014: Expert Review of Hematology
Xue-Dong Sun, Jian-Li Sang, Hui-Sheng Ai
The microchimerism is a status of the microcell or DNA of an individual in another one with genetic differences. Taking an overall view about the discovery and research of the microchimerism, it was found that although the study of the microchimerism emphasizes the formation, origin, distribution, type, relationship to disease and several other aspects, the objects of the study are always the microchimerism that obtained naturally. As it is known to all, the microchimerism can also be produced in some clinical treatment, such as in the transplant and transfusion, but compared with the microchimerism gained naturally, obviously, the study for the iatrogenic microchimerism formed in the treatment is not elaborate enough...
August 2014: Zhongguo Shi Yan Xue Ye Xue za Zhi
Hui-Hui Wu, Tie-Qiang Liu, Xue-Dong Sun, Xiao-Mei Huang, Rui Zhang, Zhi-Qiang Liu, Qiu-Hong Man, Ya-Jing Huang, Qi-Yun Sun, Hong-Li Zuo, Jian-Hui Qiao, Chang-Lin Yu, Kai-Xun Hu, Hui-Sheng Ai, Mei Guo
This study was purposed to establish and identify a H-2 completely mismatched microtransplantation model of leukemia mouse. The recipients were female BALB/c mice, while donors were male C57BL/6J mice. Recipients were inoculated intravenously with 1×10(6) of WEHI-3 cells, a cell line of myelomonocytic leukemia. Donors received 100 µg/kg G-CSF mobilization through hypodermic injection, every 12 hours, and it last 5 days. Chemotherapy regimens was MA (mitoxantrone+cytarabine), and it last 4 days. Recipients were given chemotherapy conditioning without GVHD prophylaxis after inoculation of leukemic cells for 2 days, and within 8 hours after last chemotherapy received donor mobilized spleen mononuclear cells (sMNC)...
June 2014: Zhongguo Shi Yan Xue Ye Xue za Zhi
Hong-xia Zhao, Wan-jun Sun, Mei Guo, Jie Li, Hai-lan Hu, Hui-hui Hou, Na-na Dai, Hui-sheng Ai
OBJECTIVE: To explore the efficacy and safety of HLA-mismatched stem-cell microtransplantation in patients with refractory lymphoma. METHODS: This study included 10 patients with relapsing or refractory lymphoma at Department of Hematology, Second Artillery General Hospital from October 2009 to February 2012. All patients received programmed infusions of G-CSF-mobilized HLA-mismatched donor peripheral blood stem cell (G-PBSC) after each cycle of Hyper-CVAD/MA conditioning without graft-versus-host disease (GVHD) prophylaxis...
September 10, 2013: Zhonghua Yi Xue za Zhi [Chinese medical journal]
Jie Li, Wan-jun Sun, Hong-xia Zhao, Na-na Dai, Hui-sheng Ai
No abstract text is available yet for this article.
October 2013: Zhonghua Xue Ye Xue za Zhi, Zhonghua Xueyexue Zazhi
Mingxin Zhu, Kai Shu, Heping Wang, Xiaopeng Li, Qungen Xiao, Waipan Chan, Bosomah Emmanuel, Wei Jiang, Ting Lei
Studies have demonstrated that embryonic cell therapy is a potential approach for the treatment of Huntington's disease (HD). However, because of the limited resource of embryos, greater attention is needed in developing more efficient surgical techniques that not only enhance the therapy outcome but also avoid inefficient therapeutics of transplantation. In this study, we explored the curative effects of two different transplantation methods using a rat model of HD. Whole ganglionic eminence (WGE) cells or phosphate-buffered saline were transplanted into unilateral striatum of quinolinic acid (QA)-lesioned rats using microtransplantation instruments (with an outer diameter of 50 μm) or traditional transplantation instruments (with an outer diameter of 470 μm)...
December 2013: Journal of Neuroscience Research
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