Ảnh hưởng của các nguồn tế bào trung mô stroma khác nhau và các phương pháp cung cấp trong bệnh khí phế thũng thực nghiệm

Respiratory Research - Tập 15 - Trang 1-14 - 2014
Mariana A Antunes1, Soraia C Abreu1, Fernanda F Cruz1, Ana Clara Teixeira1, Miquéias Lopes-Pacheco2, Elga Bandeira1,2, Priscilla C Olsen1, Bruno L Diaz3, Christina M Takyia4, Isalira PRG Freitas5, Nazareth N Rocha6, Vera L Capelozzi7, Débora G Xisto1,2, Daniel J Weiss8, Marcelo M Morales2, Patricia RM Rocco1
1Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute, Centro de Ciências da Saúde,, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
2Laboratory of Cellular and Molecular Physiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
3Laboratory of Inflammation, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
4Laboratory of Cellular Pathology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
5Laboratory of Cellular and Molecular Cardiology, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
6Fluminense Federal University, Niteroi, Rio de Janeiro, Brazil
7Department of Pathology, University of São Paulo, São Paulo, Brazil
8Department of Medicine, University of Vermont, Vermont, USA

Tóm tắt

Chúng tôi tiến hành đánh giá xem liệu tác động của các tế bào trung mô stroma (MSC) lên viêm phổi và tái cấu trúc phổi trong bệnh khí phế thũng thực nghiệm có khác nhau tùy thuộc vào nguồn gốc của MSC và phương pháp cung cấp hay không. Khí phế thũng được gây ra ở chuột C57BL/6 thông qua việc tiêm nội khí quản (IT) elastase tụy heo (0.1 UI) hàng tuần trong 1 tháng. Sau lần tiêm elastase cuối cùng, dung dịch muối sinh lý hoặc MSC (1-105), tách biệt từ tủy xương chuột (BM), mô mỡ (AD) hoặc mô phổi (L), đã được tiêm tĩnh mạch (IV) hoặc IT. Sau 1 tuần, chuột được tráo đổi (euthanized). Bất kể phương pháp cung cấp, MSC từ mỗi nguồn đã dẫn đến: 1) giảm số lần ngắt quãng tuyến tính trung bình, xâm nhập bạch cầu trung tính và apoptosis tế bào; 2) tăng cường hàm lượng sợi đàn hồi; 3) giảm thiệt hại tế bào biểu mô và nội mô phế nang; và 4) giảm chemokine do keratinocyte phát sinh (KC, một đồng vị chuột của interleukin-8) và mức độ yếu tố tăng trưởng chuyển hóa-β trong mô phổi. Ngược lại với IV, việc cung cấp MSC IT đã làm giảm thêm tình trạng phình phế nang (BM-MSC) và hàm lượng sợi collagen (BM-MSC và L-MSC). Việc tiêm tĩnh mạch MSC BM và AD đã giảm số lượng tế bào đại thực bào M1 và tăng huyết áp phổi trên siêu âm tim, đồng thời tăng yếu tố tăng trưởng nội mô mạch máu. Chỉ có BM-MSC (IV > IT) đã làm tăng số lượng đại thực bào M2. Tóm lại, các nguồn MSC và phương pháp cung cấp khác nhau đã giảm thiểu biến đổi phổi do elastase gây ra một cách khác nhau, nhưng việc cung cấp tĩnh mạch BM-MSC dẫn đến chức năng tim mạch tốt hơn và sự thay đổi kiểu hình đại thực bào từ M1 sang M2.

Từ khóa


Tài liệu tham khảo

Minai OA, Benditt J, Martinez FJ: Natural history of emphysema. Proc Am Thorac Soc. 2008, 5 (4): 468-474. 10.1513/pats.200802-018ET.

From the Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD).., [http://www.goldcopd.org/]

Weiss DJ: Concise review: current status of stem cells and regenerative medicine in lung biology and diseases. Stem Cells. 2014, 32 (1): 16-25. 10.1002/stem.1506.

Huh JW, Kim SY, Lee JH, Lee JS, Van Ta Q, Kim M, Oh YM, Lee YS, Lee SD: Bone marrow cells repair cigarette smoke-induced emphysema in rats. Am J Physiol Lung Cell Mol Physiol. 2011, 301 (3): L255-L266. 10.1152/ajplung.00253.2010.

Kim SY, Lee JH, Kim HJ, Park MK, Huh JW, Ro JY, Oh YM, Lee SD, Lee YS: Mesenchymal stem cell-conditioned media recovers lung fibroblasts from cigarette smoke-induced damage. Am J Physiol Lung Cell Mol Physiol. 2012, 302 (9): L891-L908. 10.1152/ajplung.00288.2011.

Schweitzer KS, Johnstone BH, Garrison J, Rush NI, Cooper S, Traktuev DO, Feng D, Adamowicz JJ, Van Demark M, Fisher AJ, Kamocki K, Brown MB, Presson RG, Broxmeyer HE, March KL, Petrache I: Adipose stem cell treatment in mice attenuates lung and systemic injury induced by cigarette smoking. Am J Respir Crit Care Med. 2011, 183 (2): 215-225. 10.1164/rccm.201001-0126OC.

Weiss DJ, Casaburi R, Flannery R, LeRoux-Williams M, Tashkin DP: A placebo-controlled, randomized trial of mesenchymal stem cells in COPD. Chest. 2013, 143 (6): 1590-1598. 10.1378/chest.12-2094.

Cruz FF, Antunes MA, Abreu SC, Fujisaki LC, Silva JD, Xisto DG, Maron-Gutierrez T, Ornellas DS, Sa VK, Rocha NN, Capelozzi VL, Morales MM, Rocco PR: Protective effects of bone marrow mononuclear cell therapy on lung and heart in an elastase-induced emphysema model. Respir Physiol Neurobiol. 2012, 182 (1): 26-36. 10.1016/j.resp.2012.01.002.

Hoffman AM, Paxson JA, Mazan MR, Davis AM, Tyagi S, Murthy S, Ingenito EP: Lung-derived mesenchymal stromal cell post-transplantation survival, persistence, paracrine expression, and repair of elastase-injured lung. Stem Cells Dev. 2011, 20 (10): 1779-1792. 10.1089/scd.2011.0105.

Guan XJ, Song L, Han FF, Cui ZL, Chen X, Guo XJ, Xu WG: Mesenchymal stem cells protect cigarette smoke-damaged lung and pulmonary function partly via VEGF-VEGF receptors. J Cell Biochem. 2013, 114 (2): 323-335. 10.1002/jcb.24377.

Ingenito EP, Tsai L, Murthy S, Tyagi S, Mazan M, Hoffman A: Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. Cell Transplant. 2012, 21 (1): 175-189. 10.3727/096368910X550233.

da Silva Meirelles L, Chagastelles PC, Nardi NB: Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci. 2006, 119 (Pt 11): 2204-2213. 10.1242/jcs.02932.

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop D, Horwitz E: Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for cellular therapy position statement. Cytotherapy. 2006, 8 (4): 315-317. 10.1080/14653240600855905.

Nora CC, Camassola M, Bellagamba B, Ikuta N, Christoff AP, Meirelles Lda S, Ayres R, Margis R, Nardi NB: Molecular analysis of the differentiation potential of murine mesenchymal stem cells from tissues of endodermal or mesodermal origin. Stem Cells Dev. 2012, 21 (10): 1761-1768. 10.1089/scd.2011.0030.

Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise J, Solomon S, Spencer KT, St John Sutton M, Stewart W: Recommendations for chamber quantification. Eur J Echocardiogr. 2006, 7 (2): 79-108. 10.1016/j.euje.2005.12.014.

Abbas AE, Franey LM, Marwick T, Maeder MT, Kaye DM, Vlahos AP, Serra W, Al-Azizi K, Schiller NB, Lester SJ: Noninvasive assessment of pulmonary vascular resistance by doppler echocardiography. J Am Soc Echocardiogr. 2013, 26 (10): 1170-1177. 10.1016/j.echo.2013.06.003.

Thibault HB, Kurtz B, Raher MJ, Shaik RS, Waxman A, Derumeaux G, Halpern EF, Bloch KD, Scherrer-Crosbie M: Noninvasive assessment of murine pulmonary arterial pressure: validation and application to models of pulmonary hypertension. Circ Cardiovasc Imaging. 2010, 3 (2): 157-163. 10.1161/CIRCIMAGING.109.887109.

Hsia CC, Hyde DM, Ochs M, Weibel ER: Structure AEJTFoQAoL: an official research policy statement of the American Thoracic Society/European Respiratory Society: standards for quantitative assessment of lung structure. Am J Respir Crit Care Med. 2010, 181 (4): 394-418. 10.1164/rccm.200809-1522ST.

Weibel ER: Morphometry: Stereological Theory and Practical Methods. Models of Lung Disease-Microscopy and Structural Methods. Edited by: Gil J. 1990, Marcel Dekker, New York, 199-247.

Antunes MA, Abreu SC, Silva AL, Parra-Cuentas ER, Ab'Saber AM, Capelozzi VL, Ferreira TP, Martins MA, Silva PM, Rocco PR: Sex-specific lung remodeling and inflammation changes in experimental allergic asthma. J Appl Physiol. 2010, 109 (3): 855-863. 10.1152/japplphysiol.00333.2010.

Abreu SC, Antunes MA, Maron-Gutierrez T, Cruz FF, Ornellas DS, Silva AL, Diaz BL, Ab'Saber AM, Capelozzi VL, Xisto DG, Morales MM, Rocco PR: Bone marrow mononuclear cell therapy in experimental allergic asthma: intratracheal versus intravenous administration. Respir Physiol Neurobiol. 2013, 185 (3): 615-624. 10.1016/j.resp.2012.11.005.

Antunes MA, Rocco PR: Elastase-induced pulmonary emphysema: insights from experimental models. An Acad Bras Cienc. 2011, 83 (4): 1385-1396. 10.1590/S0001-37652011005000039.

Ragni E, Montemurro T, Montelatici E, Lavazza C, Vigano M, Rebulla P, Giordano R, Lazzari L: Differential microRNA signature of human mesenchymal stem cells from different sources reveals an "environmental-niche memory" for bone marrow stem cells. Exp Cell Res. 2013, 319 (10): 1562-1574. 10.1016/j.yexcr.2013.04.002.

Rasmussen JG, Frobert O, Holst-Hansen C, Kastrup J, Baandrup U, Zachar V, Fink T, Simonsen U: Comparison of human adipose-derived stem cells and bone marrow-derived stem cells in a myocardial infarction model. Cell Transplant. 2012, 23 (2): 195-206. 10.3727/096368912X659871.

Rajashekhar G, Traktuev DO, Roell WC, Johnstone BH, Merfeld-Clauss S, Van Natta B, Rosen ED, March KL, Clauss M: IFATS collection: adipose stromal cell differentiation is reduced by endothelial cell contact and paracrine communication: role of canonical Wnt signaling. Stem Cells. 2008, 26 (10): 2674-2681. 10.1634/stemcells.2008-0277.

Antunes MA, Laffey JG, Pelosi P, Rocco PR: Mesenchymal stem cell trials for pulmonary diseases. J Cell Biochem. 2014, 115 (6): 1023-1032. 10.1002/jcb.24783.

Ingenito EP, Sen E, Tsai LW, Murthy S, Hoffman A: Design and testing of biological scaffolds for delivering reparative cells to target sites in the lung. J Tissue Eng Regen Med. 2010, 4 (4): 259-272. 10.1002/term.237.

Jarvinen L, Badri L, Wettlaufer S, Ohtsuka T, Standiford TJ, Toews GB, Pinsky DJ, Peters-Golden M, Lama VN: Lung resident mesenchymal stem cells isolated from human lung allografts inhibit T cell proliferation via a soluble mediator. J Immunol. 2008, 181 (6): 4389-4396. 10.4049/jimmunol.181.6.4389.

Lama VN, Smith L, Badri L, Flint A, Andrei AC, Murray S, Wang Z, Liao H, Toews GB, Krebsbach PH, Peters-Golden M, Pinsky DJ, Martinez FJ, Thannickal VJ: Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts. J Clin Invest. 2007, 117 (4): 989-996. 10.1172/JCI29713.

Curley GF, Ansari B, Hayes M, Devaney J, Masterson C, Ryan A, Barry F, O'Brien T, Toole DO, Laffey JG: Effects of intratracheal mesenchymal stromal cell therapy during recovery and resolution after ventilator-induced lung injury. Anesthesiology. 2013, 118 (4): 924-932. 10.1097/ALN.0b013e318287ba08.

Gupta N, Krasnodembskaya A, Kapetanaki M, Mouded M, Tan X, Serikov V, Matthay MA: Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax. 2012, 67 (6): 533-539. 10.1136/thoraxjnl-2011-201176.

Nystedt J, Anderson H, Tikkanen J, Pietila M, Hirvonen T, Takalo R, Heiskanen A, Satomaa T, Natunen S, Lehtonen S, Hakkarainen T, Korhonen M, Laitinen S, Valmu L, Lehenkari P: Cell surface structures influence lung clearance rate of systemically infused mesenchymal stromal cells. Stem Cells. 2013, 31 (2): 317-326. 10.1002/stem.1271.

Frankenberger M, Menzel M, Betz R, Kassner G, Weber N, Kohlhaufl M, Haussinger K, Ziegler-Heitbrock L: Characterization of a population of small macrophages in induced sputum of patients with chronic obstructive pulmonary disease and healthy volunteers. Clin Exp Immunol. 2004, 138 (3): 507-516. 10.1111/j.1365-2249.2004.02637.x.

Kunz LI, Lapperre TS, Snoeck-Stroband JB, Budulac SE, Timens W, van Wijngaarden S, Schrumpf JA, Rabe KF, Postma DS, Sterk PJ, Hiemstra PS, Groningen Leiden Universities Corticosteroids in Obstructive Lung Disease Study Group: Smoking status and anti-inflammatory macrophages in bronchoalveolar lavage and induced sputum in COPD.Respir Res 2011, 12:34.,

Shaykhiev R, Krause A, Salit J, Strulovici-Barel Y, Harvey BG, O'Connor TP, Crystal RG: Smoking-dependent reprogramming of alveolar macrophage polarization: implication for pathogenesis of chronic obstructive pulmonary disease. J Immunol. 2009, 183 (4): 2867-2883. 10.4049/jimmunol.0900473.

Salazar KD, Lankford SM, Brody AR: Mesenchymal stem cells produce Wnt isoforms and TGF-beta1 that mediate proliferation and procollagen expression by lung fibroblasts. Am J Physiol Lung Cell Mol Physiol. 2009, 297 (5): L1002-L1011. 10.1152/ajplung.90347.2008.

Takizawa H, Tanaka M, Takami K, Ohtoshi T, Ito K, Satoh M, Okada Y, Yamasawa F, Nakahara K, Umeda A: Increased expression of transforming growth factor-beta1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD). Am J Respir Crit Care Med. 2001, 163 (6): 1476-1483. 10.1164/ajrccm.163.6.9908135.

Keatings VM, Collins PD, Scott DM, Barnes PJ: Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med. 1996, 153 (2): 530-534. 10.1164/ajrccm.153.2.8564092.

Bates JH, Davis GS, Majumdar A, Butnor KJ, Suki B: Linking parenchymal disease progression to changes in lung mechanical function by percolation. Am J Respir Crit Care Med. 2007, 176 (6): 617-623. 10.1164/rccm.200611-1739OC.

Hamakawa H, Bartolak-Suki E, Parameswaran H, Majumdar A, Lutchen KR, Suki B: Structure-function relations in an elastase-induced mouse model of emphysema. Am J Respir Cell Mol Biol. 2011, 45 (3): 517-524. 10.1165/rcmb.2010-0473OC.

Winkler T, Suki B: Emergent structure-function relations in emphysema and asthma. Crit Rev Biomed Eng. 2011, 39 (4): 263-280. 10.1615/CritRevBiomedEng.v39.i4.20.