Bone marrow mesenchymal stem cells and their conditioned media could potentially ameliorate ovalbumin-induced asthmatic changes

被引:33
作者
Ahmadi, Mahdi [1 ]
Rahbarghazi, Reza [2 ,3 ]
Aslani, Mohammad Reza [1 ]
Shahbazfar, Amir-Ali [4 ]
Kazemi, Masoumeh [2 ]
Keyhanmanesh, Rana [5 ]
机构
[1] Tabriz Univ Med Sci, Fac Med, Dept Physiol, Tabriz, Iran
[2] Tabriz Univ Med Sci, Stem Cell Res Ctr, Tabriz, Iran
[3] Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Appl Cell Sci, Tabriz, Iran
[4] Univ Tabriz, Dept Pathol, Fac Vet Med, Tabriz, Iran
[5] Tabriz Univ Med Sci, Drug Appl Res Ctr, Tabriz, Iran
关键词
Asthma; Inflammation; Mesenchymal stem cells; Conditioned medium; Intratracheally; Lymphocyte; ALLERGIC AIRWAY INFLAMMATION; ACUTE LUNG INJURY; STROMAL CELLS; TRACHEAL RESPONSIVENESS; HYDROALCOHOLIC EXTRACT; MONONUCLEAR-CELLS; NIGELLA-SATIVA; MODEL; THERAPY; TRANSPLANTATION;
D O I
10.1016/j.biopha.2016.11.127
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: The major feature of asthma is governed by chronic airway inflammation. This investigation was proposed to achieve the suitable candidate for ameliorating long-term chronic asthmatic changes of respiratory tract. Methods: 36 rats were classified into healthy (C) and ovalbumin (OVA)-sensitized animals (S). To sensitize, the rats were exposed to OVA over a course of 32 +/- 1 days. One day after sensitization, equal six different groups were subjected to experimental procedure (n = 6); Rats only received intratracheally 50 ml PBS (CPT and SPT groups), 50 mu l conditioned medium (CM) (CST and SST groups) and 50 mu l PBS containing 2 x 10(6) rat bone marrow-derived mesenchymal stem cells (rBMMSCs) (CCT and SCT groups). Two weeks after treatment, tracheal responsiveness, immunologic responses and recruitment of rBMMSCs into the lung as well as pathological changes were evaluated. Results: A high degree of tracheal responsiveness, total white blood cell and percentages of eosinophil and neutrophil was significantly recorded in all sensitized groups rather than of controls (p < 0.001 to p < 0.05). Of interest, all above-mentioned parameters decreased significantly in SST and notably SCT groups as compared to S group (p < 0.001 to p < 0.05). The results revealed decrease number of blood CD3(+)CD4(+) and concurrent increase in CD3(+)CD8(+) in all sensitized rats as compared to control (p < 0.001 to p < 0.05). Noticeably, no significant modulatory effects of either cell or CM administration were achieved on the CD3(+)CD4(+) and CD3(+)CD8(+) populations in non-asthmatic rats. Moreover, the number of CD3(+)CD4(+) in SST and SCT groups tended to increase, which coincided with a decreased manner of CD3(+)CD8(+) populations as compared with S group (p < 0.001 to p < 0.05). However, the CD3(+)CD4(+) cells in SCT rats were significantly higher than the group SST (p < 0.01) whereas CD3(+)CD8(+) cells diminished simultaneously (p < 0.001). Real-time PCR analysis further showed that both CM and particularly MSCs changed the expression of interleukin (IL)-4 and IL-10 in the asthmatic groups to the near level of control rats (p < 0.001 to p < 0.05). Histopathological analysis revealed a profound reduction of lungs injuries in asthmatic rats when received CM and peculiarly mesenchymal stem cells (p < 0.01 to p < 0.05). Conclusion: Our study shed light on the superior effects of rBMMSCs, rather than CM, in attenuating of chronic asthmatic changes in the rat model. (C) 2016 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:28 / 40
页数:13
相关论文
共 73 条
[1]   Cells derived from the circulation contribute to the repair of lung injury [J].
Abe, S ;
Boyer, C ;
Liu, XD ;
Wen, FQ ;
Kobayashi, T ;
Fang, QH ;
Wang, XQ ;
Hashimoto, M ;
Sharp, JG ;
Rennard, SI .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2004, 170 (11) :1158-1163
[2]   Extracellular vesicles derived from mesenchymal stromal cells: a therapeutic option in respiratory diseases? [J].
Abreu, Soraia C. ;
Weiss, Daniel J. ;
Rocco, Patricia R. M. .
STEM CELL RESEARCH & THERAPY, 2016, 7
[3]   Effects of bone marrow mononuclear cells from healthy or ovalbumin-induced lung inflammation donors on recipient allergic asthma mice [J].
Abreu, Soraia C. ;
Antunes, Mariana A. ;
Mendonca, Lucas ;
Branco, Vivian C. ;
de Melo, Elga Bandeira ;
Olsen, Priscilla C. ;
Diaz, Bruno L. ;
Weiss, Daniel J. ;
Paredes, Bruno D. ;
Xisto, Debora G. ;
Morales, Marcelo M. ;
Rocco, Patricia R. M. .
STEM CELL RESEARCH & THERAPY, 2014, 5
[4]   Bone marrow-derived mononuclear cells vs. mesenchymal stromal cells in experimental allergic asthma [J].
Abreu, Soraia C. ;
Antunes, Mariana A. ;
de Castro, Julia C. ;
de Oliveira, Milena V. ;
Bandeira, Elga ;
Ornellas, Debora S. ;
Diaz, Bruno L. ;
Morales, Marcelo M. ;
Xisto, Debora G. ;
Rocco, Patricia R. M. .
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 2013, 187 (02) :190-198
[5]   Bone marrow mononuclear cell therapy in experimental allergic asthma: Intratracheal versus intravenous administration [J].
Abreu, Soraia C. ;
Antunes, Mariana A. ;
Maron-Gutierrez, Tatiana ;
Cruz, Fernanda F. ;
Ornellas, Debora S. ;
Silva, Adriana L. ;
Diaz, Bruno L. ;
Ab'Saber, Alexandre M. ;
Capelozzi, Vera L. ;
Xisto, Debora G. ;
Morales, Marcelo M. ;
Rocco, Patricia R. M. .
RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY, 2013, 185 (03) :615-624
[6]  
Ahmadi M., 2016, INFLAMMATION, P1
[7]   Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis [J].
Augello, Andrea ;
Tasso, Roberta ;
Negrini, Simone Maria ;
Cancedda, Ranieri ;
Pennesi, Giuseppina .
ARTHRITIS AND RHEUMATISM, 2007, 56 (04) :1175-1186
[8]   Inoperable brain metastases from non-small cell lung cancer: what part does whole brain radiotherapy play in standard treatment? [J].
Barton, Rachael .
THORAX, 2008, 63 (01) :1-2
[9]   The allergic cascade: Review of the most important molecules in the asthmatic lung [J].
Bloemen, Karollen ;
Verstraelen, Sandra ;
Van Den Heuvel, Rosette ;
Witters, Hilda ;
Nelissen, Inge ;
Schoeters, Greet .
IMMUNOLOGY LETTERS, 2007, 113 (01) :6-18
[10]   Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model [J].
Bonfield, Tracey L. ;
Koloze, Mary ;
Lennon, Donald P. ;
Zuchowski, Brandon ;
Yang, Sung Eun ;
Caplan, Arnold I. .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2010, 299 (06) :L760-L770