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Mesenchymal cell transplantation lung fibrosis

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...
March 29, 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
Y S Prakash, Daniel J Tschumperlin, Kurt R Stenmark
Lung diseases such as emphysema, interstitial fibrosis, and pulmonary vascular diseases cause significant morbidity and mortality, but despite substantial mechanistic understanding, clinical management options for them are limited, with lung transplantation being implemented at end stages. However, limited donor lung availability, graft rejection, and long-term problems after transplantation are major hurdles to lung transplantation being a panacea. Bioengineering the lung is an exciting and emerging solution that has the ultimate aim of generating lung tissues and organs for transplantation...
October 1, 2015: American Journal of Physiology. Lung Cellular and Molecular Physiology
Shi-huan Yu, Li-jie Liu, Bin Lv, Chun-li Che, Da-ping Fan, Li-feng Wang, Yi-mei Zhang
The study was aimed to investigate the mechanism and administration timing of bone marrow-derived mesenchymal stem cells (BMSCs) in bleomycin (BLM)-induced pulmonary fibrosis mice. Thirty-six mice were divided into six groups: control group (saline), model group (intratracheal administration of BLM), day 1, day 3 and day 6 BMSCs treatment groups and hormone group (hydrocortisone after BLM treatment). BMSCs treatment groups received BMSCs at day 1, 3 or 6 following BLM treatment, respectively. Haematoxylin and eosin and Masson staining were conducted to measure lung injury and fibrosis, respectively...
August 2015: Cell Biochemistry and Function
Fernanda Ferreira Cruz, Patricia Rieken Macedo Rocco
Idiopathic pulmonary fibrosis is a progressive, irreversible, debilitating, and fatal lung disease, characterized by parenchymal fibrosis with reduced lung volumes and respiratory failure. No lasting option for therapy is available other than transplantation. Mesenchymal stem/stromal cells home to sites of injury, decrease inflammation, have antifibrotic properties, and promote epithelial tissue repair, so their use has been suggested as potential therapy for idiopathic pulmonary fibrosis. Despite reported benefits, the amount of mesenchymal stromal cells engrafting to the lung decreases substantially soon after administration...
2015: Stem Cell Research & Therapy
Bin Zhou, Dan Li, Jiesheng Qian, Zhengran Li, Pengfei Pang, Hong Shan
Our previous study showed that in vivo magnetic resonance (MR) imaging is effective in tracking superparamagnetic iron oxide (SPIO)-labeled bone marrow mesenchymal stem cells (BMSCs) in rats with liver fibrosis. SPIO-labeling-induced signal reduction on MR images was completely reversed within 15 days after transplantation. It is still unclear whether the signal changes in MR imaging could reflect the number of transplanted cells in the liver. In the present study, BMSCs of male rats were doubly labeled with enhanced green fluorescent protein (EGFP) and SPIO and injected intravascularly into female rats with liver fibrosis...
November 2015: Contrast Media & Molecular Imaging
Jiabo Xu, Li Li, Jianfei Xiong, Ying Zheng, Qing Ye, Yanqin Li
INTRODUCTION: To examine the effects and possible mechanism of the immunosuppressant agent cyclophosphamide (CP) combined with bone marrow mesenchymal stromal cells (BM-MSCs) on bleomycin induced lung fibrosis in mice. METHODS: BM-MSCs labeled with red fluorescence protein (RFP) from male Friend virus B-type(FVB) mice were cultured in vitro. Pulmonary fibrosis(PF) was induced in female wild type FVB mice and mice were randomly divided into five groups: control, model, CP, BM-MSCs, and BM-MSCs+CP...
2015: Annals of Clinical and Laboratory Science
Collin T Stabler, Shimon Lecht, Philip Lazarovici, Peter I Lelkes
INTRODUCTION: Mesenchymal stem cells (MSCs) of different biological sources are in Phase 1 clinical trials and are being considered for Phase 2 therapy of lung disorders, and lung (progenitor) cells derived from pluripotent stem cells (SCs) are under development in preclinical animal models. SOURCES OF DATA: and AREAS OF AGREEMENT: There is consensus about the therapeutic potential of transplanted SCs, mainly MSCs, primarily involves paracrine 'bystander' effects that confer protection of the epithelial and endothelial linings of the lung caused by inflammation and/or fibrosis and lead to increased survival in animal models...
September 2015: British Medical Bulletin
Ying-Wei Lan, Kong-Bung Choo, Chuan-Mu Chen, Tsai-Hsien Hung, Young-Bin Chen, Chung-Hsing Hsieh, Han-Pin Kuo, Kowit-Yu Chong
INTRODUCTION: Idiopathic pulmonary fibrosis is a progressive diffuse parenchymal lung disorder of unknown etiology. Mesenchymal stem cell (MSC)-based therapy is a novel approach with great therapeutic potential for the treatment of lung diseases. Despite demonstration of MSC grafting, the populations of engrafted MSCs have been shown to decrease dramatically 24 hours post-transplantation due to exposure to harsh microenvironments. Hypoxia is known to induce expression of cytoprotective genes and also secretion of anti-inflammatory, anti-apoptotic and anti-fibrotic factors...
2015: Stem Cell Research & Therapy
Diana Álvarez, Melanie Levine, Mauricio Rojas
Idiopathic pulmonary fibrosis (IPF) is a progressive, irreversible disease of the lung that has no lasting option for therapy other than transplantation. It is characterized by replacement of the normal lung tissue by fibrotic scarring, honeycombing, and increased levels of myofibroblasts. The underlying causes of IPF are still largely unknown. The focus of the current review is the possible use of stem cell therapy, specifically mesenchymal stem cells (MSCs), a multipotent stromal cell population, which have demonstrated promising data in multiple animal models of pulmonary fibrosis (PF)...
2015: Stem Cells and Cloning: Advances and Applications
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