Comparison of reversal of rat pulmonary fibrosis of nintedanib, pirfenidone, and human umbilical mesenchymal stem cells from Wharton's jelly

被引:28
作者
Chu, Kuo-An [1 ,2 ]
Yeh, Chang-Ching [3 ,4 ,5 ]
Kuo, Fu-Hsien [6 ]
Lin, Wen-Ren [1 ]
Hsu, Chien-Wei [1 ]
Chen, Tien-Hua [6 ,7 ,8 ]
Fu, Yu-Show [9 ]
机构
[1] Kaohsiung Vet Gen Hosp, Dept Internal Med, Div Chest Med, Kaohsiung, Taiwan
[2] Natl Sun Yat Sen Univ, Inst BioPharmaceut Sci, Kaohsiung, Taiwan
[3] Taipei Vet Gen Hosp, Dept Obstet & Gynecol, Taipei, Taiwan
[4] Natl Yang Ming Univ, Inst Clin Med, Taipei, Taiwan
[5] Natl Yang Ming Univ, Dept Obstet & Gynecol, Taipei, Taiwan
[6] Natl Yang Ming Univ, Sch Med, Inst Anat & Cell Biol, Taipei, Taiwan
[7] Vet Gen Hosp, Trauma Ctr, Dept Surg, Taipei, Taiwan
[8] Vet Gen Hosp, Dept Surg, Div Gen Surg, Taipei, Taiwan
[9] Natl Yang Ming Univ, Sch Med, Dept Anat & Cell Biol, 155,Sec 2,Li Nung St, Taipei 112, Taiwan
关键词
Pulmonary fibrosis; Human umbilical mesenchymal stem cells; Nintedanib; Pirfenidone; TYROSINE KINASE INHIBITOR; BLEOMYCIN HAMSTER MODEL; NECROSIS-FACTOR-ALPHA; LUNG FIBROSIS; EFFICACY; TRANSPLANTATION; XENOGRAFT; INJURY; CORD; PDGF;
D O I
10.1186/s13287-020-02012-y
中图分类号
Q813 [细胞工程];
学科分类号
摘要
BackgroundThe present study compared the effects of antifibrotic medications, pirfenidone, and nintedanib, with transplantation of human umbilical mesenchymal stem cells (HUMSCs) in restoring rat pulmonary fibrosis (PF).MethodsA stable animal model was established via an intratracheal injection of 5mg bleomycin (BLM). One single transplantation of 2.5x 10(7) HUMSCs or initiation of daily oral nintedanib/pirfenidone administration was performed on day 21 following BLM damage.ResultsPulmonary function examination revealed that BLM rats exhibited a significant decrease in blood oxygen saturation and an increase in respiratory rates. While no significant improvements were found in BLM rats receiving nintedanib or pirfenidone, those who transplanted with HUMSCs showed a statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Quantification results revealed that a significant reduction in alveolar space and marked increases in substantial cell infiltration and collagen deposition in the left lungs of BLM rats. No significant alteration was observed in BLM rats administered nintedanib or pirfenidone. However, BLM rats transplanted with HUMSCs had a significant recovery in alveolar space and noticeable decreases in cell infiltration and collagen deposition. The inflammatory cell numbers in the bronchoalveolar lavage was increased in the BLM group. While the rats treated with nintedanib or pirfenidone had a lower cell number than the BLM group, a higher cell number was found as compared with the Normal group. In rats transplanted with HUMSCs, the cell number did not differ from the Normal group.ConclusionsTransplantation of HUMSCs could effectively treat PF as opposed to the administration of anti-fibrotic drugs with nintedanib or pirfenidone with a significant better result in lung volume, pathological changes, lung function, and blood oxygen saturation.
引用
收藏
页数:14
相关论文
共 48 条
[1]  
Amer Thoracic Soc, 2000, AM J RESP CRIT CARE, V161, P646
[2]   The role of pro- and anti-inflammatory responses in silica-induced lung fibrosis [J].
Barbarin, V ;
Nihoul, A ;
Misson, P ;
Arras, M ;
Delos, M ;
Leclercq, I ;
Lison, D ;
Huaux, F .
RESPIRATORY RESEARCH, 2005, 6 (1)
[3]   Overexpression of MMP9 in macrophages attenuates pulmonary fibrosis induced by bleomycin [J].
Cabrera, Sandra ;
Gaxiola, Miguel ;
Luis Arreola, Jose ;
Ramirez, Remedios ;
Jara, Paul ;
D'Armiento, Jeanine ;
Richards, Thomas ;
Selman, Moises ;
Pardo, Annie .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2007, 39 (12) :2324-2338
[4]   Islet-Like Clusters Derived from Mesenchymal Stem Cells in Wharton's Jelly of the Human Umbilical Cord for Transplantation to Control Type 1 Diabetes [J].
Chao, Kuo Ching ;
Chao, Kuo Fang ;
Fu, Yu Show ;
Liu, Shing Hwa .
PLOS ONE, 2008, 3 (01)
[5]   Inhibition of PDGF, VEGF and FGF signalling attenuates fibrosis [J].
Chaudhary, N. I. ;
Roth, G. J. ;
Hilberg, F. ;
Mueller-Ouernheim, J. ;
Prasse, A. ;
Zissel, G. ;
Schnapp, A. ;
Park, J. E. .
EUROPEAN RESPIRATORY JOURNAL, 2007, 29 (05) :976-985
[6]   Reversal of bleomycin-induced rat pulmonary fibrosis by a xenograft of human umbilical mesenchymal stem cells from Wharton's jelly [J].
Chu, Kuo-An ;
Wang, Shih-Yao ;
Yeh, Chang-Ching ;
Fu, Tz-Win ;
Fu, Yu-Yi ;
Ko, Tsui-Ling ;
Chiu, Mei-Miao ;
Chen, Tien-Hua ;
Tsai, Pei-Jiun ;
Fu, Yu-Show .
THERANOSTICS, 2019, 9 (22) :6646-6664
[7]   Efficacy of Nintedanib in Idiopathic Pulmonary Fibrosis across Prespecified Subgroups in INPULSIS [J].
Costabel, Ulrich ;
Inoue, Yoshikazu ;
Richeldi, Luca ;
Collard, Harold R. ;
Tschoepe, Inga ;
Stowasser, Susanne ;
Azuma, Arata .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2016, 193 (02) :178-185
[8]   Human mesenchymal stromal cells decrease the severity of acute lung injury induced by E. coli in the rat [J].
Devaney, James ;
Horie, Shahd ;
Masterson, Claire ;
Elliman, Steve ;
Barry, Frank ;
O'Brien, Timothy ;
Curley, Gerard F. ;
O'Toole, Daniel ;
Laffey, John G. .
THORAX, 2015, 70 (07) :625-635
[9]   Stem cell therapy: a potential approach for treatment of influenza virus and coronavirus-induced acute lung injury [J].
Du, Jiang ;
Li, Han ;
Lian, Jie ;
Zhu, Xinxing ;
Qiao, Liang ;
Lin, Juntang .
STEM CELL RESEARCH & THERAPY, 2020, 11 (01)
[10]   The Therapeutic Potential of Human Umbilical Mesenchymal Stem Cells From Wharton's Jelly in the Treatment of Rat Peritoneal Dialysis-Induced Fibrosis [J].
Fan, Yu-Pei ;
Hsia, Ching-Chih ;
Tseng, Kuang-Wen ;
Liao, Chih-Kai ;
Fu, Tz-Win ;
Ko, Tsui -Ling ;
Chiu, Mei-Miao ;
Shih, Yang-Hsin ;
Huang, Pei-Yu ;
Chiang, Yi-Chia ;
Yang, Chih-Ching ;
Fu, Yu-Show .
STEM CELLS TRANSLATIONAL MEDICINE, 2016, 5 (02) :235-247