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Stem Cells Translational Medicine

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https://www.readbyqxmd.com/read/28628273/exposure-of-induced-pluripotent-stem-cell-derived-vascular-endothelial-and-smooth-muscle-cells-in-coculture-to-hemodynamics-induces-primary-vascular-cell-like-phenotypes
#1
Maria S Collado, Banumathi K Cole, Robert A Figler, Mark Lawson, David Manka, Michael B Simmers, Steve Hoang, Felipe Serrano, Brett R Blackman, Sanjay Sinha, Brian R Wamhoff
Human induced pluripotent stem cells (iPSCs) can be differentiated into vascular endothelial (iEC) and smooth muscle (iSMC) cells. However, because iECs and iSMCs are not derived from an intact blood vessel, they represent an immature phenotype. Hemodynamics and heterotypic cell:cell communication play important roles in vascular cell phenotypic modulation. Here we tested the hypothesis that hemodynamic exposure of iECs in coculture with iSMCs induces an in vivo-like phenotype. iECs and iSMCs were cocultured under vascular region-specific blood flow hemodynamics, and compared to hemodynamic cocultures of blood vessel-derived endothelial (pEC) and smooth muscle (pSMC) cells...
June 19, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28618186/therapeutic-efficacy-of-fresh-allogeneic-mesenchymal-stem-cells-for-severe-refractory-feline-chronic-gingivostomatitis
#2
Boaz Arzi, Kaitlin C Clark, Ayswarya Sundaram, Mathieu Spriet, Frank J M Verstraete, Naomi J Walker, Megan R Loscar, Nasim Fazel, William J Murphy, Natalia Vapniarsky, Dori L Borjesson
Mesenchymal stem cells (MSCs) have potent immunomodulatory functions and are a promising therapy for immune-mediated inflammatory disorders. We previously demonstrated the efficacy of fresh, autologous, adipose-derived MSCs (ASCs) to treat feline chronic gingivostomatitis (FCGS), a chronic oral mucosal inflammatory disease similar to human oral lichen planus. Here, we investigate the use of fresh allogeneic ASCs for treatment of FCGS in seven cats. Radiolabeled ASCs were also tracked systemically. Each cat received two intravenous injections of 20 million ASCs, 1 month apart...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28618139/large-scale-ex-vivo-generation-of-human-red-blood-cells-from-cord-blood-cd34-cells
#3
Yu Zhang, Chen Wang, Lan Wang, Bin Shen, Xin Guan, Jing Tian, Zhihua Ren, Xinxin Ding, Yupo Ma, Wei Dai, Yongping Jiang
The ex vivo generation of human red blood cells on a large scale from hematopoietic stem and progenitor cells has been considered as a potential method to overcome blood supply shortages. Here, we report that functional human erythrocytes can be efficiently produced from cord blood (CB) CD34(+) cells using a bottle turning device culture system. Safety and efficiency studies were performed in murine and nonhuman primate (NHP) models. With the selected optimized culture conditions, one human CB CD34(+) cell could be induced ex vivo to produce up to 200 million erythrocytes with a purity of 90...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28618138/expansion-of-umbilical-cord-blood-aldehyde-dehydrogenase-expressing-cells-generates-myeloid-progenitor-cells-that-stimulate-limb-revascularization
#4
David M Putman, Tyler T Cooper, Stephen E Sherman, Ayesh K Seneviratne, Mark Hewitt, Gillian I Bell, David A Hess
Uncompromised by chronic disease-related comorbidities, human umbilical cord blood (UCB) progenitor cells with high aldehyde dehydrogenase activity (ALDH(hi) cells) stimulate blood vessel regeneration after intra-muscular transplantation. However, implementation of cellular therapies using UCB ALDH(hi) cells for critical limb ischemia, the most severe form of severe peripheral artery disease, is limited by the rarity (<0.5%) of these cells. Our goal was to generate a clinically-translatable, allogeneic cell population for vessel regenerative therapies, via ex vivo expansion of UCB ALDH(hi) cells without loss of pro-angiogenic potency...
June 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28585336/liver-directed-human-amniotic-epithelial-cell-transplantation-improves-systemic-disease-phenotype-in-hurler-syndrome-mouse-model
#5
Natalie S Rodriguez, Lisa Yanuaria, Kevin Murphy R Parducho, Irving M Garcia, Bino A Varghese, Brendan H Grubbs, Toshio Miki
Mucopolysaccharidosis type 1 (MPS1) is an inherited lysosomal storage disorder caused by a deficiency in the glycosaminoglycan (GAG)-degrading enzyme α-l-iduronidase (IDUA). In affected patients, the systemic accumulation of GAGs results in skeletal dysplasia, neurological degeneration, multiple organ dysfunction, and early death. Current therapies, including enzyme replacement and bone marrow transplant, improve life expectancy but the benefits to skeletal and neurological phenotypes are limited. In this study, we tested the therapeutic efficacy of liver-directed transplantation of a placental stem cell, which possesses multilineage differentiation potential, low immunogenicity, and high lysosomal enzyme activity...
June 6, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28504874/cranioplasty-with-adipose-derived-stem-cells-beta-tricalcium-phosphate-granules-and-supporting-mesh-six-year-clinical-follow-up-results
#6
Tuomo Thesleff, Kai Lehtimäki, Tero Niskakangas, Sanna Huovinen, Bettina Mannerström, Susanna Miettinen, Riitta Seppänen-Kaijansinkko, Juha Öhman
Several alternative techniques exist to reconstruct skull defects. The complication rate of the cranioplasty procedure is high and the search for optimal materials and techniques continues. To report long-term results of patients who have received a cranioplasty using autologous adipose-derived stem cells (ASCs) seeded on beta-tricalcium phosphate (betaTCP) granules. Between 10/2008 and 3/2010, five cranioplasties were performed (four females, one male; average age 62.0 years) using ASCs, betaTCP granules and titanium or resorbable meshes...
May 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28504860/allogeneic-bone-marrow-derived-mesenchymal-stromal-cells-expanded-in-vitro-for-treatment-of-aplastic-anemia-a-multicenter-phase-ii-trial
#7
Yan Pang, Hao-Wen Xiao, Hang Zhang, Zeng-Hui Liu, Li Li, Yang Gao, Hong-Bo Li, Zu-Jun Jiang, Huo Tan, Jing-Ren Lin, Xin Du, Jian-Yu Weng, Da-Nian Nie, Dong-Jun Lin, Xiang-Zhong Zhang, Qi-Fa Liu, Duo-Rong Xu, Hai-Jia Chen, Xiao-Hu Ge, Xiao-Yan Wang, Yang Xiao
We conducted a phase II, noncomparative, multicenter study to assess the efficacy and safety of allogeneic bone marrow-derived mesenchymal stromal cells (BM-MSCs) expanded in vitro for patients with aplastic anemia (AA) refractory to immunosuppressive therapy. Seventy-four patients from seven centers received allogeneic BM-MSCs at a dose of 1-2 × 10(6) cells/kg per week for 4 weeks. Responses were assessed at 0.5, 1, 2, 3, 6, 9, and 12 months after the first cells infusion. Patients with response at 1 month continued to receive four infusions...
May 15, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28488282/concise-review-wharton-s-jelly-the-rich-but-enigmatic-source-of-mesenchymal-stromal-cells
#8
John E Davies, John T Walker, Armand Keating
The umbilical cord has become an increasingly used source of mesenchymal stromal cells for preclinical and, more recently, clinical studies. Despite the increased activity, several aspects of this cell population have been under-appreciated. Key issues are that consensus on the anatomical structures within the cord is lacking, and potentially different populations are identified as arising from a single source. To help address these points, we propose a histologically based nomenclature for cord structures and provide an analysis of their developmental origins and composition...
May 10, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28474513/bone-marrow-endothelial-progenitor-cells-are-the-cellular-mediators-of-pulmonary-hypertension-in-the-murine-monocrotaline-injury-model
#9
Jason M Aliotta, Mandy Pereira, Sicheng Wen, Mark S Dooner, Michael Del Tatto, Elaine Papa, Yan Cheng, Laura Goldberg, Corey E Ventetuolo, Olin Liang, James R Klinger, Peter J Quesenberry
The role of bone marrow (BM) cells in modulating pulmonary hypertensive responses is not well understood. Determine if BM-derived endothelial progenitor cells (EPCs) induce pulmonary hypertension (PH) and if this is attenuated by mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs). Three BM populations were studied: (a) BM from vehicle and monocrotaline (MCT)-treated mice (PH induction), (b) BM from vehicle-, MCT-treated mice that received MSC-EV infusion after vehicle, MCT treatment (PH reversal, in vivo), (c) BM from vehicle-, MCT-treated mice cultured with MSC-EVs (PH reversal, in vitro)...
May 5, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28467694/durable-control-of-autoimmune-diabetes-in-mice-achieved-by-intraperitoneal-transplantation-of-neo-islets-three-dimensional-aggregates-of-allogeneic-islet-and-mesenchymal-stem-cells
#10
Christof Westenfelder, Anna Gooch, Zhuma Hu, Jon Ahlstrom, Ping Zhang
Novel interventions that reestablish endogenous insulin secretion and thereby halt progressive end-organ damage and prolong survival of patients with autoimmune Type 1 diabetes mellitus (T1DM) are urgently needed. While this is currently accomplished with allogeneic pancreas or islet transplants, their utility is significantly limited by both the scarcity of organ donors and life-long need for often-toxic antirejection drugs. Coadministering islets with bone marrow-derived mesenchymal stem cells (MSCs) that exert robust immune-modulating, anti-inflammatory, anti-apoptotic, and angiogenic actions, improves intrahepatic islet survival and function...
May 3, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28544662/tracheal-replacement-therapy-with-a-stem-cell-seeded-graft-lessons-from-compassionate-use-application-of-a-gmp-compliant-tissue-engineered-medicine
#11
Martin J Elliott, Colin R Butler, Aikaterini Varanou-Jenkins, Leanne Partington, Carla Carvalho, Edward Samuel, Claire Crowley, Peggy Lange, Nicholas J Hamilton, Robert E Hynds, Tahera Ansari, Paul Sibbons, Anja Fierens, Claire McLaren, Derek Roebuck, Colin Wallis, Nagarajan Muthialu, Richard Hewitt, David Crabbe, Sam M Janes, Paolo De Coppi, Mark W Lowdell, Martin A Birchall
Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use of tissue-engineered tracheae in compassionate use cases suggests that such an approach is a viable option. Here, a stem cell-seeded, decellularized tissue-engineered tracheal graft was used on a compassionate basis for a girl with critical tracheal stenosis after conventional reconstructive techniques failed. The graft represents the first cell-seeded tracheal graft manufactured to full good manufacturing practice (GMP) standards...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28544661/early-passage-mesenchymal-stem-cells-display-decreased-radiosensitivity-and-increased-dna-repair-activity
#12
Po-Kuei Wu, Jir-You Wang, Cheng-Fong Chen, Kuang-Yu Chao, Ming-Chau Chang, Wei-Ming Chen, Shih-Chieh Hung
Cell therapies using human mesenchymal stem cells (MSCs) have received much attention in the past decade. In pursuit of the therapeutic potential of MSCs, cell expansion is required to generate a great number of cells with desired phenotype and functionality. Long-term expansion in vitro, however, can lead to altered functions. To explore the changes in DNA damage responses (DDR) in MSCs expanded, DDR pathways following irradiation were characterized in early- and late-passage bone marrow MSCs. Seventy-two hours after irradiation, the percentage of sub-G1 cells in early-passage MSCs did not change significantly...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28481046/human-neural-stem-cell-biodistribution-and-predicted-tumor-coverage-by-a-diffusible-therapeutic-in-a-mouse-glioma-model
#13
Michael E Barish, Kelsey Herrmann, Yang Tang, Siranush Argalian Herculian, Marianne Metz, Soraya Aramburo, Revathiswari Tirughana, Margarita Gutova, Alexander Annala, Rex A Moats, Leanne Goldstein, Russell C Rockne, Jennifer Gutierrez, Christine E Brown, Lucy Ghoda, Karen S Aboody
Engineered neural stem cells (NSCs) intrinsically migrating to brain tumors offer a promising mechanism for local therapeutic delivery. However, difficulties in quantitative assessments of NSC migration and in estimates of tumor coverage by diffusible therapeutics have impeded development and refinement of NSC-based therapies. To address this need, we developed techniques by which conventional serial-sectioned formalin-fixed paraffin-embedded (FFPE) brains can be analyzed in their entirety across multiple test animals...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28474838/connective-tissue-growth-factor-promotes-efficient-generation-of-human-induced-pluripotent-stem-cell-derived-choroidal-endothelium
#14
Allison E Songstad, Kristan S Worthington, Kathleen R Chirco, Joseph C Giacalone, S Scott Whitmore, Kristin R Anfinson, Dalyz Ochoa, Cathryn M Cranston, Megan J Riker, Maurine Neiman, Edwin M Stone, Robert F Mullins, Budd A Tucker
Age-related macular degeneration (AMD) is a leading cause of irreversible blindness in the Western world. Although, the majority of stem cell research to date has focused on production of retinal pigment epithelial (RPE) and photoreceptor cells for the purpose of evaluating disease pathophysiology and cell replacement, there is strong evidence that the choroidal endothelial cells (CECs) that form the choriocapillaris vessels are the first to be lost in this disease. As such, to accurately evaluate disease pathophysiology and develop an effective treatment, production of patient-specific, stem cell-derived CECs will be required...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28452204/mesenchymal-stem-cells-time-to-change-the-name
#15
Arnold I Caplan
Mesenchymal stem cells (MSCs) were officially named more than 25 years ago to represent a class of cells from human and mammalian bone marrow and periosteum that could be isolated and expanded in culture while maintaining their in vitro capacity to be induced to form a variety of mesodermal phenotypes and tissues. The in vitro capacity to form bone, cartilage, fat, etc., became an assay for identifying this class of multipotent cells and around which several companies were formed in the 1990s to medically exploit the regenerative capabilities of MSCs...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28425576/bone-marrow-adipose-and-lung-tissue-derived-murine-mesenchymal-stromal-cells-release-different-mediators-and-differentially-affect-airway-and-lung-parenchyma-in-experimental-asthma
#16
Soraia C Abreu, Mariana A Antunes, Debora G Xisto, Fernanda F Cruz, Vivian C Branco, Elga Bandeira, Jamil Zola Kitoko, Almair F de Araújo, Ludmilla Dellatorre-Texeira, Priscilla C Olsen, Daniel J Weiss, Bruno L Diaz, Marcelo M Morales, Patricia R M Rocco
Mesenchymal stromal cells (MSCs) from different sources have differential effects on lung injury. To compare the effects of murine MSCs from bone marrow (BM), adipose tissue (AD), and lung tissue (LUNG) on inflammatory and remodeling processes in experimental allergic asthma, female C57BL/6 mice were sensitized and challenged with ovalbumin (OVA) or saline (C). Twenty-four hours after the last challenge, mice received either saline (50 µl, SAL), BM-MSCs, AD-MSCs, or LUNG-MSCs (10(5) cells per mouse in 50 µl total volume) intratracheally...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28371411/generation-of-integration-free-induced-pluripotent-stem-cells-from-urine-derived-cells-isolated-from-individuals-with-down-syndrome
#17
Young M Lee, Bruna L Zampieri, Jonah J Scott-McKean, Mark W Johnson, Alberto C S Costa
Down syndrome (DS) is a genetic disorder caused by trisomy 21 (T21). Over the past two decades, the use of mouse models has led to significant advances in the understanding of mechanisms underlying various phenotypic features and comorbidities secondary to T21 and even informed the design of clinical trials aimed at enhancing the cognitive abilities of persons with DS. In spite of its success, this approach has been plagued by all the typical limitations of rodent modeling of human disorders and diseases. Recently, several laboratories have succeeded in producing T21 human induced pluripotent stem cells (T21-iPSCs) from individuals with DS, which is emerging as a promising complementary tool for the study of DS...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28337852/turning-potential-into-action-using-pluripotent-stem-cells-to-understand-heart-development-and-function-in-health-and-disease
#18
Hananeh Fonoudi, Alexis Bosman
Pluripotent stem cells hold enormous potential for regenerative therapies, however their ability to provide insight into early human development and the origins of disease could arguably provide an even greater outcome. This is primarily due to their contribution to the establishment of a powerful knowledge base of human development, something which all researchers and clinicians can potentially benefit from. Modeling human heart development and disease using pluripotent stem cells has already provided many important insights into cardiogenesis and cardiovascular disease mechanisms however, it is important to be aware of the complexities of this model system...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28296283/effects-of-transendocardial-cd34-cell-transplantation-on-diastolic-parameters-in-patients-with-nonischemic-dilated-cardiomyopathy
#19
Mojca Bervar, Mirta Kozelj, Gregor Poglajen, Matjaz Sever, Gregor Zemljic, Sabina Frljak, Marko Cukjati, Peter Cernelc, François Haddad, Bojan Vrtovec
We sought to evaluate the physiological background and the effects of CD34(+) cell transplantation on diastolic parameters in nonischemic dilated cardiomyopathy patients (DCM). We enrolled 38 DCM patients with NYHA class III and LVEF < 40% who underwent transendocardial CD34(+) cell transplantation. Peripheral blood CD34(+) cells were mobilized by G-CSF, collected via apheresis, and injected transendocardially in the areas of myocardial hibernation. Patients were followed for 1 year. At baseline, estimated filling pressures were significantly elevated (E/e' ≥ 15) in 18 patients (Group A), and moderately elevated (E/e '< 15) in 20 patients (Group B)...
June 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28244243/angiotensin-ii-causes-apoptosis-of-adult-hippocampal-neural-stem-cells-and-memory-impairment-through-the-action-on-ampk-pgc1%C3%AE-signaling-in-heart-failure
#20
Min-Seok Kim, Geun-Hee Lee, Yong-Min Kim, Byoung-Wook Lee, Hae Yun Nam, U-Cheol Sim, Suk-Jung Choo, Seong-Woon Yu, Jae-Joong Kim, Yunhee Kim Kwon, Seong Who Kim
Data are limited on the mechanisms underlying memory impairment in heart failure (HF). We hypothesized that angiotensin II (Ang II) may determine the fate of adult hippocampal neural stem cells (HCNs), a cause of memory impairment in HF. HCNs with neurogenesis potential were isolated and cultured from adult rat hippocampi. Ang II decreased HCN proliferation in dose- and time-dependent manners. Moreover, Ang II treatment (1 µM) for 48 hours induced apoptotic death, which was attenuated by pretreatment with Ang II receptor blockers (ARBs)...
June 2017: Stem Cells Translational Medicine
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