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Adipose-derived regenerative cell therapy inhibits the progression of monocrotaline-induced pulmonary hypertension in rats


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Title: Adipose-derived regenerative cell therapy inhibits the progression of monocrotaline-induced pulmonary hypertension in rats
Other Titles: 脂肪由来幹細胞(ADRCs)を用いた細胞移植療法の肺動脈性肺高血圧症モデルラットへの有効性の検討とそのメカニズムの解明
Authors: 江口, 正倫
Authors (alternative): Eguchi, Masamichi
Issue Date: 18-Mar-2015
Publisher: Elsevier Inc.
Citation: Nagasaki University (長崎大学), 博士(医学) (2015-03-18)
Abstract: Aims Functional and structural changes in pulmonary vasculature characterize pulmonary arterial hypertension (PAH) and the prognosis of advanced PAH remains poor despite progress in pharmacotherapy. Adipose-derived regenerative cells (ADRCs) promote cell regeneration at pathological sites and comprise a novel therapy for ailments of various organs. We investigated the effects of ADRC therapy in rat models of monocrotaline (MCT)-induced pulmonary hypertension (PH) and the underlying mechanisms. Main methods Rats were assigned to Control and MCT groups without and with (M/A) intravenous transfusion of seven million ADRCs on day 7. We echocardiographically evaluated pulmonary hypertension as pulmonary artery flow acceleration time (PAAT) and deceleration (PADc). Right ventricular (RV) systolic pressure was measured by catheterization on day 28 and then pathological changes in pulmonary vessels were assessed. We analyzed PAH-associated gene expression on day 14 using real-time RT-PCR. Key findings Echocardiography and RV catheterization showed that ADRC therapy inhibited PH development (assessed as PAAT, PADc, and RV systolic pressure) at day 28 (MCT vs. M/A, P < 0.05). Pulmonary vascular remodeling was also inhibited (vessel wall thickness: MCT vs. M/A, P < 0.01). Messenger RNA levels of endothelin (ET) A and B receptors, ET-1 and transforming growth factor (TGF)-β increased in the lungs by MCT were suppressed by ADRCs (MCT vs. M/A, P < 0.05). Significance The development of PH was inhibited by ADRCs through suppressing changes in the expression of genes associated with ET and TGF-β systems. We believe that ADRC therapy could serve as a novel strategy for treating PH.
Description: 長崎大学学位論文 学位記番号:博(医歯薬)乙第38号 学位授与年月日:平成27年3月18日 / Author: Masamichi Eguchi, Satoshi Ikeda, Saburo Kusumoto, Daisuke Sato, Yuji Koide, Hiroaki Kawano, Koji Maemura / Citation: Life Sciences, 118(2), pp.306-315; 2014
Keywords: Endothelin-1 / Transforming growth factor beta / Pulmonary hypertension / Adipose derived regenerative cell (ADRC)
URI: http://hdl.handle.net/10069/35495
ISSN: 00243205
DOI: 10.1016/j.lfs.2014.05.008
Relational Links: http://hdl.handle.net/10069/35656
Rights: © 2014 The Authors. Published by Elsevier Inc. / This is an openaccess article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Type: Thesis or Dissertation
Text Version: ETD
Appears in Collections:dissertation

Citable URI : http://hdl.handle.net/10069/35495

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