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Stem Cells Translational Medicine

Jean L Tan, Yan Z Tan, Ruth Muljadi, Siow T Chan, Sin N Lau, Joanne C Mockler, Euan M Wallace, Rebecca Lim
: : Human amnion epithelial cells (hAECs) have been shown to possess potent immunomodulatory properties across a number of disease models. Recently, we reported that hAECs influence macrophage polarization and activity, and that this step was dependent on regulatory T cells. In this study, we aimed to assess the effects of hAEC-derived proresolution lipoxin-A4 (LXA4) on T-cell, macrophage, and neutrophil phenotype and function during the acute phase of bleomycin-induced lung injury. Using C57Bl6 mice, we administered 4 million hAECs intraperitoneally 24 hours after bleomycin challenge...
November 7, 2016: Stem Cells Translational Medicine
Jie Chen, Zhaoyuan Yuan, Yu Liu, Rui Zheng, Yao Dai, Ran Tao, Huitang Xia, Hairong Liu, Zhiyong Zhang, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
: : In vitro three-dimensional (3D) cartilage regeneration is a promising strategy for repair of cartilage defects. However, inferior mechanical strength and tissue homogeneity greatly restricted its clinical translation. Simulation of mechanical stress through a bioreactor is an important approach for improving in vitro cartilage regeneration. The current study developed a hydrostatic pressure (HP) bioreactor based on a novel pressure-transmitting mode achieved by slight deformation of a flexible membrane in a completely sealed stainless steel device...
November 7, 2016: Stem Cells Translational Medicine
Katherine L B Knorr, Laura E Finn, B Douglas Smith, Allan D Hess, James M Foran, Judith E Karp, Scott H Kaufmann
: : Current understanding suggests that malignant stem and progenitor cells must be reduced or eliminated for prolonged remissions in myeloid neoplasms such as acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS). Multicolor flow cytometry has been widely used to distinguish stem and myeloid progenitor cells from other populations in normal and malignant bone marrow. In this study, we present a method for assessing drug sensitivity in MDS and AML patient hematopoietic stem and myeloid progenitor cell populations ex vivo using the investigational Nedd8-activating enzyme inhibitor MLN4924 and standard-of-care agent cytarabine as examples...
November 7, 2016: Stem Cells Translational Medicine
Shi-Cong Tao, Shang-Chun Guo, Min Li, Qin-Fei Ke, Ya-Ping Guo, Chang-Qing Zhang
: : There is a need to find better strategies to promote wound healing, especially of chronic wounds, which remain a challenge. We found that synovium mesenchymal stem cells (SMSCs) have the ability to strongly promote cell proliferation of fibroblasts; however, they are ineffective at promoting angiogenesis. Using gene overexpression technology, we overexpressed microRNA-126-3p (miR-126-3p) and transferred the angiogenic ability of endothelial progenitor cells to SMSCs, promoting angiogenesis...
October 26, 2016: Stem Cells Translational Medicine
Xiaoxi Xu, Xiaochun Li, Xiangying Gu, Bai Zhang, Weijun Tian, Hongqiu Han, Peng Sun, Caigan Du, Hao Wang
: : Endometrial regenerative cells (ERCs) have been recently evaluated as an attractive candidate source for emerging stem cell therapies in immunosuppression, but their role in immunoregulation is not fully understood. The present study was designed to investigate their effects, especially on B-cell responses in heart transplantation. In this study, ERCs were noninvasively obtained from menstrual blood. Heart transplantation was performed between C57BL/6 (H-2(b)) donor mice and BALB/c (H-2(d)) recipients...
October 26, 2016: Stem Cells Translational Medicine
Scott M Riester, Janet M Denbeigh, Yang Lin, Dakota L Jones, Tristan de Mooij, Eric A Lewallen, Hai Nie, Christopher R Paradise, Darcie J Radel, Amel Dudakovic, Emily T Camilleri, Dirk R Larson, Wenchun Qu, Aaron J Krych, Matthew A Frick, Hee-Jeong Im, Allan B Dietz, Jay Smith, Andre J van Wijnen
: : Adipose-derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra-articular joint space. Culture-expanded human AMSCs grown in human platelet-lysate were delivered via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy...
October 26, 2016: Stem Cells Translational Medicine
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December 2016: Stem Cells Translational Medicine
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December 2016: Stem Cells Translational Medicine
Elena Serena, Susi Zatti, Alice Zoso, Francesca Lo Verso, F Saverio Tedesco, Giulio Cossu, Nicola Elvassore
: : Restoration of the protein dystrophin on muscle membrane is the goal of many research lines aimed at curing Duchenne muscular dystrophy (DMD). Results of ongoing preclinical and clinical trials suggest that partial restoration of dystrophin might be sufficient to significantly reduce muscle damage. Different myogenic progenitors are candidates for cell therapy of muscular dystrophies, but only satellite cells and pericytes have already entered clinical experimentation. This study aimed to provide in vitro quantitative evidence of the ability of mesoangioblasts to restore dystrophin, in terms of protein accumulation and distribution, within myotubes derived from DMD patients, using a microengineered model...
December 2016: Stem Cells Translational Medicine
Yan Long, Miao Xu, Rong Li, Sheng Dai, Jeanette Beers, Guokai Chen, Ferri Soheilian, Ulrich Baxa, Mengqiao Wang, Juan J Marugan, Silvia Muro, Zhiyuan Li, Roscoe Brady, Wei Zheng
: : Niemann-Pick disease type A (NPA) is a lysosomal storage disease caused by mutations in the SMPD1 gene that encodes acid sphingomyelinase (ASM). Deficiency in ASM function results in lysosomal accumulation of sphingomyelin and neurodegeneration. Currently, there is no effective treatment for NPA. To accelerate drug discovery for treatment of NPA, we generated induced pluripotent stem cells from two patient dermal fibroblast lines and differentiated them into neural stem cells. The NPA neural stem cells exhibit a disease phenotype of lysosomal sphingomyelin accumulation and enlarged lysosomes...
December 2016: Stem Cells Translational Medicine
Jia-Min Zhang, Fei-Er Feng, Qian-Ming Wang, Xiao-Lu Zhu, Hai-Xia Fu, Lan-Ping Xu, Kai-Yan Liu, Xiao-Jun Huang, Xiao-Hui Zhang
: : Immune thrombocytopenia (ITP) is characterized by platelet destruction and megakaryocyte dysfunction. Mesenchymal stem cells (MSCs) from ITP patients (MSC-ITP) do not exhibit conventional proliferative abilities and thus exhibit defects in immunoregulation, suggesting that MSC impairment might be a mechanism involved in ITP. Platelet-derived growth factor (PDGF) improves growth and survival in various cell types. Moreover, PDGF promotes MSC proliferation. The aim of the present study was to analyze the effects of PDGF-BB on MSC-ITP...
December 2016: Stem Cells Translational Medicine
Guihua Jiang, Todd J Herron, Julie Di Bernardo, Kendal A Walker, K Sue O'Shea, Shaun M Kunisaki
: : The establishment of an abundant source of autologous cardiac progenitor cells would represent a major advance toward eventual clinical translation of regenerative medicine strategies in children with prenatally diagnosed congenital heart disease. In support of this concept, we sought to examine whether functional, transgene-free human cardiomyocytes (CMs) with potential for patient-specific and autologous applications could be reliably generated following routine amniocentesis. Under institutional review board approval, amniotic fluid specimens (8-10 ml) at 20 weeks gestation were expanded and reprogrammed toward pluripotency using nonintegrating Sendai virus (SeV) expressing OCT4, SOX2, cMYC, and KLF4...
December 2016: Stem Cells Translational Medicine
Shannon R Moore, Céline Heu, Nicole Y C Yu, Renee M Whan, Ulf R Knothe, Stefan Milz, Melissa L Knothe Tate
: : An abundance of surgical studies during the past 2 centuries provide empirical evidence of periosteum's regenerative power for reconstructing tissues as diverse as trachea and bone. This study aimed to develop quantitative, efficacy-based measures, thereby providing translational guidelines for the use of periosteum to harness the body's own healing potential and generate target tissues. The current study quantitatively and qualitatively demonstrated tissue generation modulated by a periosteum substitute membrane that replicates the structural constituents of native periosteum (elastin, collagen, progenitor cells) and its barrier, extracellular, and cellular properties...
December 2016: Stem Cells Translational Medicine
Jeroen Plessers, Emily Dekimpe, Matthias Van Woensel, Valerie D Roobrouck, Dominique M Bullens, Jef Pinxteren, Catherine M Verfaillie, Stefaan W Van Gool
: : MultiStem cells are clinical-grade multipotent adult bone marrow-derived progenitor cells (MAPCs), with extensive replication potential and broader differentiation capacity compared with mesenchymal stem cells. Human MAPCs suppress T-cell proliferation induced by alloantigens and mutually interact with allogeneic natural killer cells. In this study, the interaction between MultiStem and CD8(+) cytotoxic T lymphocytes (CTLs) was addressed for the first time. In an in vitro setting, the immunogenicity of MultiStem, the susceptibility of MultiStem toward CTL-mediated lysis, and its effects on CTL function were investigated...
December 2016: Stem Cells Translational Medicine
Eric G Schmuck, Jill M Koch, John M Centanni, Timothy A Hacker, Rudolf K Braun, Marlowe Eldridge, Derek J Hei, Peiman Hematti, Amish N Raval
: : Cell tracking is a critical component of the safety and efficacy evaluation of therapeutic cell products. To date, cell-tracking modalities have been hampered by poor resolution, low sensitivity, and inability to track cells beyond the shortterm. Three-dimensional (3D) cryo-imaging coregisters fluorescent and bright-field microcopy images and allows for single-cell quantification within a 3D organ volume. We hypothesized that 3D cryo-imaging could be used to measure cell biodistribution and clearance after intravenous infusion in a rat lung injury model compared with normal rats...
December 2016: Stem Cells Translational Medicine
Yanhui Li, Yan Wen, Zhe Wang, Yi Wei, Prachi Wani, Morgaine Green, Ganesh Swaminathan, Anand Ramamurthi, Renee Reijo Pera, Bertha Chen
: : Data suggest that myoblasts from various sources, including bone marrow, skeletal muscle, and adipose tissue, can restore muscle function in patients with urinary incontinence. Animal data have indicated that these progenitor cells exert mostly a paracrine effect on the native tissues rather than cell regeneration. Limited knowledge is available on the in vivo effect of human stem cells or muscle progenitors on injured muscles. We examined in vivo integration of smooth muscle progenitor cells (pSMCs) derived from human pluripotent stem cells (hPSCs)...
December 2016: Stem Cells Translational Medicine
Kapka Miteva, Sophie Van Linthout, Kathleen Pappritz, Irene Müller, Frank Spillmann, Marion Haag, Harald Stachelscheid, Jochen Ringe, Michael Sittinger, Carsten Tschöpe
: : Cardiac-derived adherent proliferating cells (CardAPs) are cells derived from human endomyocardial biopsy specimens; they share several properties with mesenchymal stromal cells. The aims of this study were to evaluate whether intramyocardial injection of CardAPs modulates cardiac fibrosis and hypertrophy in a mouse model of angiotensin II (Ang II)-induced systolic heart failure and to analyze underlying mechanisms. Intramyocardial application of 200,000 CardAPs improved left ventricular function...
December 2016: Stem Cells Translational Medicine
Anna Marsano, Carolina M Medeiros da Cunha, Shahram Ghanaati, Sinan Gueven, Matteo Centola, Roman Tsaryk, Mike Barbeck, Chiara Stuedle, Andrea Barbero, Uta Helmrich, Stefan Schaeren, James C Kirkpatrick, Andrea Banfi, Ivan Martin
: : Chondrogenic differentiation of bone marrow-derived mesenchymal stromal/stem cells (MSCs) can be induced by presenting morphogenetic factors or soluble signals but typically suffers from limited efficiency, reproducibility across primary batches, and maintenance of phenotypic stability. Considering the avascular and hypoxic milieu of articular cartilage, we hypothesized that sole inhibition of angiogenesis can provide physiological cues to direct in vivo differentiation of uncommitted MSCs to stable cartilage formation...
December 2016: Stem Cells Translational Medicine
Chengcheng Cui, Xinchun Ye, Michael Chopp, Poornima Venkat, Alex Zacharek, Tao Yan, Ruizhou Ning, Peng Yu, Guiyun Cui, Jieli Chen
: : In rats with type 1 diabetes (T1DM), the therapeutic effects and underlying mechanisms of action of stroke treatment were compared between bone-marrow stromal cells (BMSCs) derived from T1DM rats (DM-BMSCs) and BMSCs derived from normal rats (Nor-BMSCs). The novel role of microRNA-145 (miR-145) in mediating DM-BMSC treatment-induced benefits was also investigated. T1DM rats (n = 8 per group) underwent 2 hours of middle cerebral artery occlusion (MCAo) and were treated 24 hours later with the one of the following (5 × 10(6) cells administered i...
December 2016: Stem Cells Translational Medicine
Taisuke Furuta, Shigeru Miyaki, Hiroyuki Ishitobi, Toshihiko Ogura, Yoshio Kato, Naosuke Kamei, Kenji Miyado, Yukihito Higashi, Mitsuo Ochi
: : Paracrine signaling by bone-marrow-derived mesenchymal stem cells (MSCs) plays a major role in tissue repair. Although the production of regulatory cytokines by MSC transplantation is a critical modulator of tissue regeneration, we focused on exosomes, which are extracellular vesicles that contain proteins and nucleic acids, as a novel additional modulator of cell-to-cell communication and tissue regeneration. To address this, we used radiologic imaging, histological examination, and immunohistochemical analysis to evaluate the role of exosomes isolated from MSC-conditioned medium (CM) in the healing process in a femur fracture model of CD9(-/-) mice, a strain that is known to produce reduced levels of exosomes...
December 2016: Stem Cells Translational Medicine
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