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https://www.readbyqxmd.com/read/28110217/induced-dopaminergic-neurons-a-new-promise-for-parkinson-s-disease
#1
Zhimin Xu, Xingkun Chu, Houbo Jiang, Haley Schilling, Shengdi Chen, Jian Feng
Motor symptoms that define Parkinson's disease (PD) are caused by the selective loss of nigral dopaminergic (DA) neurons. Cell replacement therapy for PD has been focused on midbrain DA neurons derived from human fetal mesencephalic tissue, human embryonic stem cells (hESC) or human induced pluripotent stem cells (iPSC). Recent development in the direct conversion of human fibroblasts to induced dopaminergic (iDA) neurons offers new opportunities for transplantation study and disease modeling in PD. The iDA neurons are generated directly from human fibroblasts in a short period of time, bypassing lengthy differentiation process from human pluripotent stem cells and the concern for potentially tumorigenic mitotic cells...
January 16, 2017: Redox Biology
https://www.readbyqxmd.com/read/28110104/quercetin-3-o-glucuronide-promotes-the-proliferation-and-migration-of-neural-stem-cells
#2
Samrat Baral, Ramesh Pariyar, Jaehyo Kim, Ho-Sub Lee, Jungwon Seo
Quercetin is a bioactive compound exerting therapeutic effects on in vivo animal models of neurodegeneration or neurotoxicity. However, the narrow therapeutic dose-range of quercetin has been a point of concern since previous studies have demonstrated that quercetin induces cytotoxicity in vitro. Quercetin is metabolized to quercetin glucuronates such as quercetin-3-O-glucuronide (Q3GA), primarily detected in the plasma and the brain. Here, we examined whether and how quercetin or Q3GA regulates neural stem cells (NSCs) in vivo and in vitro...
January 3, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28109879/selenomethionine-promoted-hippocampal-neurogenesis-via-the-pi3k-akt-gsk3%C3%AE-wnt-pathway-in-a-mouse-model-of-alzheimer-s-disease
#3
REVIEW
Rui Zheng, Zhong-Hao Zhang, Chen Chen, Yao Chen, Shi-Zheng Jia, Qiong Liu, Jia-Zuan Ni, Guo-Li Song
The maintenance of neural system integrity and function is the ultimate goal for the treatment of neurodegenerative disease such as Alzheimer's disease (AD). Neurogenesis plays an integral role in the maintenance of neural and cognitive functions, and its dysfunction is regarded as a major cause of cognitive impairment in AD. Moreover, the induction of neurogenesis by targeting endogenous neural stem cells (NSCs) is considered as one of the most promising treatment strategies. Our previous studies demonstrated that selenomethionine (Se-Met) was able to reduce β-amyloid peptide (Aβ) deposition, decrease Tau protein hyperphosphorylation and markedly improve cognitive functions in triple transgenic (3xTg) AD mice...
January 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28107865/adipose-tissue-derived-stem-cells-ameliorates-dermal-fibrosis-in-a-mouse-model-of-scleroderma
#4
Wei Chen, Zhi-Kuan Xia, Man-Hui Zhang, Gui-Chun Ding, Xiao-Yan Zhang, Zheng-Xu Wang, Rong-Ya Yang
OBJECTIVE: To investigate the therapeutic potential of adipose-derived stem cells (ADSCs) for limited cutaneous scleroderma (LS) in mouse models. METHODS: ADSCs were isolated from pathogen-free female C57BL/6 mice and LS was induced in wild type (WT) C57BL/6 mice via daily injection of bleomycin (0.1 mL × 300 μg/mL) for 4 weeks; then the ADSCs were subcutaneously injected into the dorsal area in the model treatment group, and 100 μL of phosphate-buffered saline (PBS) solution was injected into the same site in the model control group...
January 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/28107194/transdifferentiation-of-human-male-germline-stem-cells-to-hepatocytes-in-vivo-via-the-transplantation-under-renal-capsules
#5
Zheng Chen, Minghui Niu, Min Sun, Qingqing Yuan, Chencheng Yao, Jingmei Hou, Hong Wang, Liping Wen, Hongyong Fu, Fan Zhou, Zheng Li, Zuping He
Here we proposed a new concept that human spermatogonial stem cells (SSCs) can transdifferentiate into hepatocytes in vivo. We first established liver injury model of mice by carbon tetrachloride to provide proper environment for human SSC transplantation. Liver mesenchymal cells were isolated from mice and identified phenotypically. Human SSC line was recombined with liver mesenchymal cells, and they were transplanted under renal capsules of nude mice with liver injury. The grafts expressed hepatocyte hallmarks, including ALB, AAT, CK18, and CYP1A2, whereas germ cell and SSC markers VASA and GPR125 were undetected in these cells, implicating that human SSCs were converted to hepatocytes...
January 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28103944/a-comparison-between-allogeneic-stem-cell-transplantation-from-unmanipulated-haploidentical-and-unrelated-donors-in-acute-leukemia
#6
Simona Piemontese, F Ciceri, M Labopin, W Arcese, S Kyrcz-Krzemien, S Santarone, H Huang, D Beelen, N C Gorin, C Craddock, Z Gulbas, A Bacigalupo, M Mohty, A Nagler
BACKGROUND: In the absence of a HLA-matched related or matched unrelated donor, allogeneic stem cell transplantation (allo-SCT) from mismatched unrelated donors or haploidentical donors are potential alternatives for patients with acute leukemia with an indication to allo-SCT. The objective of this study was to compare the outcome of allo-SCT from T cell-replete haploidentical (Haplo) versus matched (MUD 10/10) or mismatched unrelated donor at a single HLA-locus (MMUD 9/10) for patients with acute leukemia in remission...
January 19, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28103599/evaluations-of-intravenous-administration-of-cd34-human-umbilical-cord-blood-cells-in-a-mouse-model-of-neonatal-hypoxic-ischemic-encephalopathy
#7
Makiko Ohshima, Akihiko Taguchi, Yoshiaki Sato, Yuko Ogawa, Satoshi Saito, Kenichi Yamahara, Masafumi Ihara, Mariko Harada-Shiba, Tomoaki Ikeda, Tomohiro Matsuyama, Masahiro Tsuji
Several cell therapies have been explored as novel therapeutic strategies for neonatal encephalopathy because the benefits of current treatments are limited. We previously reported that intravenous administration of human umbilical cord blood (hUCB) CD34+ cells (hematopoietic stem cells/endothelial progenitor cells) at 48 h after insult exerts therapeutic effects in neonatal mice with stroke, i.e., permanent middle cerebral artery occlusion. Although neonatal stroke and hypoxic-ischemic encephalopathy (HIE) are grouped under the term "neonatal encephalopathy," their pathogenesis differs...
January 20, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28103576/a-new-model-of-multi-visceral-and-bone-metastatic-prostate-cancer-with-perivascular-niche-targeting-by-a-novel-endothelial-specific-adenoviral-vector
#8
Zhi Hong Lu, Sergey Kaliberov, Rebecca E Sohn, Lyudmila Kaliberova, Yingqiu Du, Julie L Prior, Daniel J Leib, Anne Chauchereau, Jennifer K Sehn, David T Curiel, Jeffrey M Arbeit
While modern therapies for metastatic prostate cancer (PCa) have improved survival they are associated with an increasingly prevalent entity, aggressive variant PCa (AVPCa), lacking androgen receptor (AR) expression, enriched for cancer stem cells (CSCs), and evidencing epithelial-mesenchymal plasticity with a varying extent of neuroendocrine transdifferentiation. Parallel work revealed that endothelial cells (ECs) create a perivascular CSC niche mediated by juxtacrine and membrane tethered signaling. There is increasing interest in pharmacological metastatic niche targeting, however, targeted access has been impossible...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28102896/impact-of-pre-transplant-depression-on-outcomes-of-allogeneic-and-autologous-hematopoietic-stem-cell-transplantation
#9
Areej El-Jawahri, Yi-Bin Chen, Ruta Brazauskas, Naya He, Stephanie J Lee, Jennifer M Knight, Navneet Majhail, David Buchbinder, Raquel M Schears, Baldeep M Wirk, William A Wood, Ibrahim Ahmed, Mahmoud Aljurf, Jeff Szer, Sara M Beattie, Minoo Battiwalla, Christopher Dandoy, Miguel-Angel Diaz, Anita D'Souza, Cesar O Freytes, James Gajewski, Usama Gergis, Shahrukh K Hashmi, Ann Jakubowski, Rammurti T Kamble, Tamila Kindwall-Keller, Hilard M Lazarus, Adriana K Malone, David I Marks, Kenneth Meehan, Bipin N Savani, Richard F Olsson, David Rizzieri, Amir Steinberg, Dawn Speckhart, David Szwajcer, Helene Schoemans, Sachiko Seo, Celalettin Ustun, Yoshiko Atsuta, Jignesh Dalal, Carmem Sales-Bonfim, Nandita Khera, Theresa Hahn, Wael Saber
BACKGROUND: To evaluate the impact of depression before autologous and allogeneic hematopoietic cell transplantation (HCT) on clinical outcomes posttransplantation. METHODS: We analyzed data from the Center for International Blood and Marrow Transplant Research to compare outcomes after autologous (n = 3786) or allogeneic (n = 7433) HCT for adult patients with hematologic malignancies with an existing diagnosis of pre-HCT depression requiring treatment versus those without pre-HCT depression...
January 19, 2017: Cancer
https://www.readbyqxmd.com/read/28102837/precise-and-efficient-scarless-genome-editing-in-stem-cells-using-correct
#10
Dylan Kwart, Dominik Paquet, Shaun Teo, Marc Tessier-Lavigne
CRISPR/Cas9 is a promising tool for genome-editing DNA in cells with single-base-pair precision, which allows novel in vitro models of human disease to be generated-e.g., in pluripotent stem cells. However, the accuracy of intended sequence changes can be severely diminished by CRISPR/Cas9's propensity to re-edit previously modified loci, causing unwanted mutations (indels) alongside intended changes. Here we describe a genome-editing framework termed consecutive re-guide or re-Cas steps to erase CRISPR/Cas-blocked targets (CORRECT), which, by exploiting the use of highly efficacious CRISPR/Cas-blocking mutations in two rounds of genome editing, enables accurate, efficient and scarless introduction of specific base changes-for example, in human induced pluripotent (iPS) stem cells...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28102490/genome-engineering-of-stem-cell-organoids-for-disease-modeling
#11
REVIEW
Yingmin Sun, Qiurong Ding
Precision medicine emerges as a new approach that takes into account individual variability. Successful realization of precision medicine requires disease models that are able to incorporate personalized disease information and recapitulate disease development processes at the molecular, cellular and organ levels. With recent development in stem cell field, a variety of tissue organoids can be derived from patient specific pluripotent stem cells and adult stem cells. In combination with the state-of-the-art genome editing tools, organoids can be further engineered to mimic disease-relevant genetic and epigenetic status of a patient...
January 19, 2017: Protein & Cell
https://www.readbyqxmd.com/read/28100889/cotransfer-of-regulatory-t-cells-improve-the-therapeutic-effectiveness-of-mesenchymal-stem-cells-in-treating-a-colitis-mouse-model
#12
Yang Yu, Tianyu Zhao, Deqin Yang
Inflammatory bowel disease (IBD) is a severe inflammatory condition in the colon. To date, clinical solutions for this disease have been limited. Mesenchymal stem cells (MSCs), multipotential cells with immune regulation and anti-inflammatory functions, have been applied to treatment of IBD. However, the therapeutic effectiveness of MSCs still needs to be improved. Here, we were interested in whether regulatory T cells (Tregs) could enhance the immune regulation function of MSCs in treatment of mouse colitis...
January 19, 2017: Experimental Animals
https://www.readbyqxmd.com/read/28099150/elimination-of-quiescent-slow-cycling-cells-via-reducing-quiescence-depth-by-natural-compounds-purified-from-ganoderma-lucidum
#13
Jian Dai, Matthew A Miller, Nicholas J Everetts, Xia Wang, Peng Li, Ye Li, Jian-Hua Xu, Guang Yao
The medical mushroom Ganoderma lucidum has long been used in traditional Chinese medicine and shown effective in the treatment of many diseases including cancer. Here we studied the cytotoxic effects of two natural compounds purified from Ganoderma lucidum, ergosterol peroxide and ganodermanondiol. We found that these two compounds exhibited cytotoxicity not only against fast proliferating cells, but on quiescent, slow-cycling cells. Using a fibroblast cell-quiescence model, we found that the cytotoxicity on quiescent cells was due to induced apoptosis, and was associated with a shallower quiescent state in compound-treated cells, resultant from the increased basal activity of an Rb-E2F bistable switch that controls quiescence exit...
January 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098348/impact-of-lysosomal-storage-disorders-on-biology-of-mesenchymal-stem-cells-evidences-from-in-vitro-silencing-of-glucocerebrosidase-gba-and-alpha-galactosidase-a-gla-enzymes
#14
T Squillaro, I Antonucci, N Alessio, A Esposito, M Cipollaro, Mab Melone, G Peluso, L Stuppia, U Galderisi
Lysosomal storage disorders (LDS) comprise a group of rare multisystemic diseases resulting from inherited gene mutations that impair lysosomal homeostasis. The most common LSDs, Gaucher disease (GD) and Fabry disease (FD) are caused by deficiencies in the lysosomal glucocerebrosidase (GBA) and alpha-galactosidase A (GLA) enzymes, respectively. Given the systemic nature of enzyme deficiency, we hypothesized that the stem cell compartment of GD and FD patients might be also affected. Among stem cells, mesenchymal stem cells (MSCs) are a commonly investigated population given their role in hematopoiesis and the homeostatic maintenance of many organs and tissues...
January 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28098218/the-role-of-mir-497-5p-in-myofibroblast-differentiation-of-lr-mscs-and-pulmonary-fibrogenesis
#15
Xiang Chen, Chaowen Shi, Cong Wang, Weilin Liu, Yanhong Chu, Zou Xiang, Kebin Hu, Ping Dong, Xiaodong Han
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive and fatal fibrotic lung disease characterized by profound changes in stem cell differentiation, epithelial cell phenotypes and fibroblast proliferation. In our study, we found that miR-497-5p was significantly upregulated both during myofibroblast differentiation of lung resident mesenchymal stem cells (LR-MSCs) and in the lung tissues of a pulmonary fibrosis model. In addition, as determined by luciferase assays and Western blot analysis, reversion-inducing cysteine-rich protein with kazal motifs (Reck) was identified to be one of the target genes of miR-497-5p, and Reck could suppress the expression of matrix metalloproteinase-2 (Mmp2) and Mmp9, which could activate latent transforming growth factor-β1 (TGF-β1)...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28096964/g-csf-for-mobilizing-transplanted-bone-marrow-stem-cells-in-rat-model-of-parkinson-s-disease
#16
Manouchehr Safari, Behnaz Jafari, Sam Zarbakhsh, Hamidreza Sameni, Abbas Ali Vafaei, Nasrin Khan Mohammadi, Laya Ghahari
OBJECTIVES: Granulocyte-colony stimulating factor (G-CSF) is used in clinical practice for the treatment of neutropenia and to stimulate generation of hematopoietic stem cells in bone marrow donors. In the present study, the ability of G-CSF in mobilizing exogenous bone marrow stem cells (BMSCs) from peripheral blood into the brain was tested. We for the first time injected a small amount of BMSCs through the tail vein. MATERIALS AND METHODS: We choose 25 male Wistar rats (200-250 g) were lesioned by 6-OHDA injected into the left substantia nigra, pars compacta (SNpc)...
December 2016: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28096272/anti-leukemia-efficacy-and-mechanisms-of-action-of-sl-101-a-novel-anti-cd123-antibody-conjugate-in-acute-myeloid-leukemia
#17
Lina Han, Jeffrey L Jorgensen, Christopher Brooks, Ce Shi, Qi Zhang, Graciela M Nogueras González, Antonio Cavazos, Rongqing Pan, Hong Mu, Sa Wang, Jin Zhou, Gheath Alatrash, Stefan O Ciurea, Michael Rettig, John F DiPersio, Jorge E Cortes, Xuelin Huang, Hagop Kantarjian, Michael Andreeff, Farhad Ravandi-Kashani, Marina Konopleva
PURPOSE: The persistence of leukemia stem cells (LSC)-containing cells after induction therapy may contribute to minimal residual disease (MRD) and relapse in acute myeloid leukemia (AML). We investigated the clinical relevance of CD34+CD123+ LSC-containing cells and anti-leukemia potency of a novel antibody-conjugate SL-101 in targeting CD123+ LSCs. Experimental Methods and Results: In a retrospective study on 86 newly diagnosed AML patients, we demonstrated that a higher proportion of CD34+CD123+ LSC-containing cells in remission was associated with persistent MRD, and predicted shorter relapse-free survival in patients with poor-risk cytogenetics...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28096185/transcriptomic-profiling-of-purified-patient-derived-dopamine-neurons-identifies-convergent-perturbations-and-therapeutics-for-parkinson-s-disease
#18
Cynthia Sandor, Paul Robertson, Charmaine Lang, Andreas Heger, Heather Booth, Jane Vowles, Lorna Witty, Rory Bowden, Michele Hu, Sally A Cowley, Richard Wade-Martins, Caleb Webber
While induced pluripotent stem cell (iPSC) technologies enable the study of inaccessible patient cell types, cellular heterogeneity can confound the comparison of gene expression profiles between iPSC-derived cell lines. Here, we purified iPSC-derived human dopaminergic neurons (DaNs) using the intracellular marker, tyrosine hydroxylase. Once purified, the transcriptomic profiles of iPSC-derived DaNs appear remarkably similar to profiles obtained from mature post-mortem DaNs. Comparison of the profiles of purified iPSC-derived DaNs derived from Parkinson's disease (PD) patients carrying LRRK2 G2019S variants to controls identified significant functional convergence amongst differentially-expressed (DE) genes...
January 17, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28096093/lymphangiogenesis-is-a-feature-of-acute-gvhd-and-vegfr-3-inhibition-protects-against-experimental-gvhd
#19
Sarah Mertlitz, Yu Shi, Martina Kalupa, Carsten Grötzinger, Jörg Mengwasser, Katarina Riesner, Steffen Cordes, Sefer Elezkurtaj, Olaf Penack
Lymph vessels play a crucial role for immune reactions in health and disease. In oncology the inhibition of lymphangiogenesis is an established therapeutic concept to reduce metastatic spreading of tumor cells. During allogeneic tissue transplantation the inhibition of lymphangiogenesis has been successfully used to attenuate graft rejection. Despite its critical importance for tumor growth, allo-immune responses and inflammation, the role of lymphangiogenesis has not been investigated during allogeneic hematopoietic stem cell transplantation (allo-HSCT)...
January 17, 2017: Blood
https://www.readbyqxmd.com/read/28095625/potentiation-of-biological-effects-of-mesenchymal-stem-cells-in-ischemic-conditions-by-melatonin-via-upregulation-of-cellular-prion-protein-expression
#20
Jun Hee Lee, Yong-Seok Han, Sang Hun Lee
Mesenchymal stem cells (MSCs) are promising candidates for stem cell-based therapy in ischemic diseases. However, ischemic injury induces pathophysiological conditions, such as oxidative stress and inflammation, which diminish therapeutic efficacy of MSC-based therapy by reducing survival and functionality of transplanted MSCs. To overcome this problem, we explored the effects of melatonin on the proliferation, resistance to oxidative stress, and immunomodulatory properties of MSCs. Treatment with melatonin enhanced MSC proliferation and self-renewal via upregulation of cellular prion protein (PrP(C) ) expression...
January 17, 2017: Journal of Pineal Research
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