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Mesenchymal cell transplantation lung fibrosis

Bingyu Xiang, Lu Chen, Xiaojun Wang, Yongjia Zhao, Yanling Wang, Charlie Xiang
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high morbidity and mortality. Menstrual blood-derived stem cells (MenSCs) have been shown to be good therapeutic tools in diseases such as ovarian failure and cardiac fibrosis. However, relevant studies of MenSCs in ALI have not yet proceeded. We hypothesized that MenSC could attenuate the inflammation in lipopolysaccharide (LPS)-induced ALI and promote the repair of damaged lung. ALI model was induced by LPS in C57 mice, and saline or MenSCs were administered via tail vein after four hours...
March 27, 2017: International Journal of Molecular Sciences
Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong-Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong
Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs...
March 2017: Stem Cells Translational Medicine
Pengxiu Cao, Yoshiro Aoki, Linda Badri, Natalie M Walker, Casey M Manning, Amir Lagstein, Eric R Fearon, Vibha N Lama
Tissue fibrosis is the primary cause of long-term graft failure after organ transplantation. In lung allografts, progressive terminal airway fibrosis leads to an irreversible decline in lung function termed bronchiolitis obliterans syndrome (BOS). Here, we have identified an autocrine pathway linking nuclear factor of activated T cells 2 (NFAT1), autotaxin (ATX), lysophosphatidic acid (LPA), and β-catenin that contributes to progression of fibrosis in lung allografts. Mesenchymal cells (MCs) derived from fibrotic lung allografts (BOS MCs) demonstrated constitutive nuclear β-catenin expression that was dependent on autocrine ATX secretion and LPA signaling...
April 3, 2017: Journal of Clinical Investigation
Dan C Wilkinson, Jackelyn A Alva-Ornelas, Jennifer M S Sucre, Preethi Vijayaraj, Abdo Durra, Wade Richardson, Steven J Jonas, Manash K Paul, Saravanan Karumbayaram, Bruce Dunn, Brigitte N Gomperts
Stem cell technologies, especially patient-specific, induced stem cell pluripotency and directed differentiation, hold great promise for changing the landscape of medical therapies. Proper exploitation of these methods may lead to personalized organ transplants, but to regenerate organs, it is necessary to develop methods for assembling differentiated cells into functional, organ-level tissues. The generation of three-dimensional human tissue models also holds potential for medical advances in disease modeling, as full organ functionality may not be necessary to recapitulate disease pathophysiology...
February 2017: Stem Cells Translational Medicine
Masahiro Iseki, Yoshihiro Kushida, Shohei Wakao, Takahiro Akimoto, Masamichi Mizuma, Fuyuhiko Motoi, Ryuta Asada, Shinobu Shimizu, Michiaki Unno, Gregorio Chazenbalk, Mari Dezawa
Muse cells, a novel type of non-tumorigenic pluripotent-like stem cells reside in the bone marrow, skin and adipose tissue, are collectable as cells positive for pluripotent surface marker SSEA-3. They are able to differentiate into cells representative of all three germ layers. The capacity of intravenously injected human bone marrow-Muse cells to repair the liver fibrosis model of immunodeficient mice was evaluated in this study. They exhibited the ability for differentiation spontaneously into hepatoblast/hepatocyte-lineage cells and high migration toward the serum and liver tissue of carbon tetrachloride-treated mice in vitro...
November 2, 2016: Cell Transplantation
Yan Zhou, Zhong He, Yuan Gao, Rui Zheng, Xiaoye Zhang, Li Zhao, Mingqi Tan
Pulmonary fibrosis is a progressive and irreversible fibrotic lung disorder with high mortality and few treatment options. Recently, induced pluripotent stem (iPS) cells have been considered as an ideal resource for stem cell-based therapy. Although, an earlier study demonstrated the therapeutic effect of iPS cells on pulmonary fibrosis, the exact mechanisms remain obscure. The present study investigated the effects of iPS cells on inflammatory responses, transforming growth factor (TGF)-β1 signaling pathway, and epithelial to mesenchymal transition (EMT) during bleomycin (BLM)-induced lung fibrosis...
2016: Frontiers in Pharmacology
Ying-Wei Lan, Si-Min Theng, Tsung-Teng Huang, Kong-Bung Choo, Chuan-Mu Chen, Han-Pin Kuo, Kowit-Yu Chong
: Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs...
October 18, 2016: Stem Cells Translational Medicine
Wook-Jin Chung
Pulmonary arterial hypertension (PAH) is a life-threatening disorder with a poor prognosis and causes pulmonary vascular remodeling accompanied with increased pulmonary arterial medial wall thickness and fibrosis, which leads to vascular and right ventricular (RV) dysfunction. Despite treatment with prostacyclin, endothelin antagonist, and phosphodiesterase-5 inhibitors the 1-year mortality rate of PAH still remains high. Recent registries, clinical trials, and basic researches have been increasing the knowledge of PAH and it would contribute to potential therapeutic strategies and better clinical outcome...
September 2016: Journal of Hypertension
Sophie Wecht, Mauricio Rojas
Mesenchymal stem cells (MSCs) are a populace of non-haematopoietic multipotent stromal cells, which have the ability to differentiate into tissue derived from a single germ layer. MSCs have been isolated from various sites, including adipose tissue, skeletal muscle, synovium, spleen, thymus, lung and amniotic fluid, but are most often isolated from bone marrow. MSCs have several valuable functions that make them a promising therapeutic option in the field of regenerative medicine, including the secretion of anti-inflammatory cytokines and growth factors, the migration of cells to the site of injury when administered and the ability to 'rescue' cells through the transfer of functional mitochondria...
November 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
Jin Tao, Qinglun Li, Xiaowei Ma, Fei Han, Xiaoming Liu, Jun Wei, Yongzhao Zhu
Objective To investigate the therapeutic effect and mechanism of human placental mesenchymal stem cells of fetal origin (hfPMSCs) cultured in serum-free medium on mouse pulmonary fibrosis induced by bleomycin treatment. Methods Human hfPMSCs were cultured and identified by flow cytometry. Fifteen 6-week-old male SPF C57BL/6J mice were divided into 3 groups: bleomycin treatment group, hfPMSCs transplantation group and negative control group. Pulmonary fibrosis model was induced in the mice of bleomycin treatment group and hfPMSCs transplantation group with bleomycin (1 μg/L, 50 μL) via intratracheal instillation...
October 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Osamu Watanabe, Takao Tsuji, Ryota Kikuchi, Masayuki Itoh, Hiroyuki Nakamura, Kazutetsu Aoshiba
Recent evidence suggests that epithelial-mesenchymal transition (EMT) is involved in the pathogenesis of airway obstructive diseases, such as chronic obstructive pulmonary disease, asthma and bronchiolitis obliterans syndrome after lung transplantation. However, whether EMT occurs in an experimental model of airway fibrosis is not well known. We explored evidence of EMT in a murine model of airway fibrosis induced by repeated exposure to naphthalene. Mice were administered intraperitoneal injections of naphthalene or corn oil vehicle once weekly for 14 consecutive weeks...
October 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
Paola Tomei, Valentina Masola, Simona Granata, Gloria Bellin, Pierluigi Carratù, Miriam Ficial, Valentina Anna Ventura, Maurizio Onisto, Onofrio Resta, Giovanni Gambaro, Marco Chilosi, Antonio Lupo, Gianluigi Zaza
BACKGROUND: Everolimus (EVE) is a mammalian target of rapamycin inhibitor (mTOR-I) widely used in transplantation that may determine some severe adverse events, including pulmonary fibrosis. The pathogenic mechanism of mTOR-I-associated pulmonary toxicity is still unclear, but epithelial to mesenchymal transition (EMT) of bronchial/pulmonary cells may play a role. METHODS: Three cell lines-human type II pneumocyte-derived A549, normal bronchial epithelial, and bronchial epithelial homozygous for the delta F508 cystic fibrosis-causing mutation-were treated with EVE or tacrolimus at different concentrations...
December 2016: Journal of Nephrology
Masato Uji, Akira Nakada, Tatsuo Nakamura, Kazuto Hirata
BACKGROUND: Mesenchymal stromal cells (MSCs) have been intensively investigated in regenerative medicine. Among the different types of MSCs, adipose tissue-derived stromal cells (ASCs) can be obtained with relatively less invasive techniques. Since ASC administration is a candidate strategy for the treatment of refractory diseases including pulmonary fibrosis, we investigated whether intratracheal injection of ASCs had therapeutic potential against bleomycin (BLM)-induced lung injury in rats...
December 2015: Osaka City Medical Journal
Ashish R Kurundkar, Deepali Kurundkar, Sunad Rangarajan, Morgan L Locy, Yong Zhou, Rui-Ming Liu, Jaroslaw Zmijewski, Victor J Thannickal
Matricellular proteins mediate pleiotropic effects during tissue injury and repair. CCN1 is a matricellular protein that has been implicated in angiogenesis, inflammation, and wound repair. In this study, we identified CCN1 as a gene that is differentially up-regulated in alveolar mesenchymal cells of human subjects with rapidly progressive idiopathic pulmonary fibrosis (IPF). Elevated levels of CCN1 mRNA were confirmed in lung tissues of IPF subjects undergoing lung transplantation, and CCN1 protein was predominantly localized to fibroblastic foci...
June 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Mohamed S A Mohamed
With the increased incidence of lung and other organ failure, organ transplantation becomes a frequent surgical intervention. Research is focused on improving the practice of lung and other organ transplantation in order to improve the clinical outcome and to decrease the incidence of post-operative complications. This manuscript represents the author's view of the possibility of improving the lung transplantation outcome through the co-transplantation of mesenchymal stem cells, and the expected positive effects of that application...
2015: Journal of Stem Cells
Jun Tashiro, Sharon J Elliot, David J Gerth, Xiaomei Xia, Simone Pereira-Simon, Rhea Choi, Paola Catanuto, Shahriar Shahzeidi, Rebecca L Toonkel, Rahil H Shah, Fadi El Salem, Marilyn K Glassberg
The observation that pulmonary inflammatory lesions and bleomycin (BLM)-induced pulmonary fibrosis spontaneously resolve in young mice, whereas remaining irreversible in aged mice suggests that impairment of pulmonary regeneration and repair is associated with aging. Because mesenchymal stem cells (MSCs) may promote repair after injury, we postulated that differences in MSCs from aged mice may underlie postinjury fibrosis in aging. The potential for young-donor MSCs to inhibit BLM-induced pulmonary fibrosis in aged male mice (>22 months) has not been studied...
December 2015: Translational Research: the Journal of Laboratory and Clinical Medicine
X Zhou, H Loomis-King, S J Gurczynski, C A Wilke, K E Konopka, C Ptaschinski, S M Coomes, Y Iwakura, L F van Dyk, N W Lukacs, B B Moore
Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-γ production...
May 2016: Mucosal Immunology
Eric Henry, Jhon Cores, M Taylor Hensley, Shirena Anthony, Adam Vandergriff, James B M de Andrade, Tyler Allen, Thomas G Caranasos, Leonard J Lobo, Ke Cheng
UNLABELLED: Lung diseases are devastating conditions and ranked as one of the top five causes of mortality worldwide according to the World Health Organization. Stem cell therapy is a promising strategy for lung regeneration. Previous animal and clinical studies have focused on the use of mesenchymal stem cells (from other parts of the body) for lung regenerative therapies. We report a rapid and robust method to generate therapeutic resident lung progenitors from adult lung tissues. Outgrowth cells from healthy lung tissue explants are self-aggregated into three-dimensional lung spheroids in a suspension culture...
November 2015: Stem Cells Translational Medicine
Shirong Ni, Dexuan Wang, Xiaoxiao Qiu, Lingxia Pang, Zhangjuan Song, Kunyuan Guo
UNLABELLED: Pulmonary fibrosis is a progressive and lethal disorder. Although the precise mechanisms of pulmonary fibrosis are not fully understood, oxidant/antioxidant may play an important role in many of the processes of inflammation and fibrosis. Keap1-Nrf2-ARE pathway represents one of the most important cellular defense mechanisms against oxidative stress. Mesenchymal stem cells (MSC) are in clinical trials for widespread indications including musculoskeletal, neurological, cardiac and haematological disorders...
2015: International Journal of Clinical and Experimental Pathology
Dong Kyung Sung, Yun Sil Chang, So Yoon Ahn, Se In Sung, Hye Soo Yoo, Soo Jin Choi, Soo Yoon Kim, Won Soon Park
The aim of this study was to determine the optimal route of mesenchymal stem cell (MSC) transplantation. To this end, gene expression profiling was performed to compare the effects of intratracheal (i.t.) versus intravenous (i.v.) MSC administration. Furthermore, the therapeutic efficacy of each route to protect against neonatal hyperoxic lung injury was also determined. Newborn Sprague-Dawley rats were exposed to hyperoxia (90% oxygen) from birth for 14 days. Human umbilical cord blood-derived MSCs labeling with PKH26 were transplanted through either the i...
2015: PloS One
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