Exosomes in mesenchymal stem cells, a new therapeutic strategy for cardiovascular diseases?

International Journal of Biological Sciences

Volumn 11, Issue 2, 2015, Pages 238-245

  Huang, Lina ^a   Ma, Wenya ^a   Ma, Yidi ^a   Feng, Dan ^a   Chen, Hongyang ^a   Cai, Benzhi ^a  

^a HARBIN MEDICAL UNIVERSITY   (China)

Author keywords

Exosomes; Mesenchymal stem cell; MicroRNA; Myocardial infarction; Pulmonary hypertension; Reperfusion injury

Indexed keywords

ANIMAL; CARDIOVASCULAR DISEASES; CYTOLOGY; EXOSOME; HUMAN; MESENCHYMAL STROMA CELL; METABOLISM; PHYSIOLOGY;

ANIMALS; CARDIOVASCULAR DISEASES; EXOSOMES; HUMANS; MESENCHYMAL STROMAL CELLS;

EID: 84921926547     PISSN: 14492288     EISSN: None     Source Type: Journal    
DOI: 10.7150/ijbs.10725     Document Type: Review

References (90)

1. Christoforou N, Gearhart JD. Stem cells and their potential in cell-based cardiac therapies. Prog Cardiovasc Dis. 2007; 49: 396-413. doi: 10.1016/j.pcad.2007.02.006.
2. Wu JY, Liao C, Xu ZP, Chen JS, Gu SL. [A modified method to isolate and identify the adult mesenchymal stem cells from human bone marrow]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006; 14: 557-60.
3. Mazzetti MP, Oliveira IS, Miranda-Ferreira R, Fauaz G, Ribeiro CN, Gomes PO, et al. Qualitative and quantitative analysis of rabbit's fat mesenchymal stem cells. Acta Cir Bras. 2010; 25: 24-7.
4. Zhang MW, Guo ZK, Liu XD, Wu Y, Hou CM, Mao N. [Development of methodology for isolation and culture of mesenchymal stem cells derived from mouse skeletal muscle]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2003; 11: 538-41. doi:1009-2137(2003)05-0538-04.
5. Ling L, Ni Y, Wang Q, Wang H, Hao S, Hu Y, et al. Transdifferentiation of mesenchymal stem cells derived from human fetal lung to hepatocyte-like cells. Cell Biol Int. 2008; 32: 1091-8. doi:10.1016/j.cellbi.2008.04.020.
6. Gotherstrom C, Ringden O, Westgren M, Tammik C, Le Blanc K. Immunomodulatory effects of human foetal liver-derived mesenchymal stem cells. Bone Marrow Transplant. 2003; 32: 265-72. doi:10.1038/sj.bmt.1704111.
7. Cao H, Chu Y, Zhu H, Sun J, Pu Y, Gao Z, et al. Characterization of immortalized mesenchymal stem cells derived from foetal porcine pancreas. Cell Prolif. 2011; 44: 19-32. doi:10.1111/j.1365-2184.2010.00714.x.
8. Lee JC, Min HJ, Park HJ, Lee S, Seong SC, Lee MC. Synovial membrane- derived mesenchymal stem cells supported by platelet-rich plasma can repair osteochondral defects in a rabbit model. Arthroscopy. 2013; 29: 1034-46. doi:10.1016/j.arthro.2013.02.026.
9. Rust PA, Kalsi P, Briggs TW, Cannon SR, Blunn GW. Will mesenchymal stem cells differentiate into osteoblasts on allograft? Clin Orthop Relat Res. 2007; 457: 220-6. doi:10.1097/BLO.0b013e31802e7e8f.
10. Morganstein DL, Wu P, Mane MR, Fisk NM, White R, Parker MG. Human fetal mesenchymal stem cells differentiate into brown and white adipocytes: a role for ERRalpha in human UCP1 expression. Cell Res. 2010; 20: 434-44. doi: 10.1038/cr.2010.11.
11. Zhang X, Hirai M, Cantero S, Ciubotariu R, Dobrila L, Hirsh A, et al. Isolation and characterization of mesenchymal stem cells from human umbilical cord blood: reevaluation of critical factors for successful isolation and high ability to proliferate and differentiate to chondrocytes as compared to mesenchymalstem cells from bone marrow and adipose tissue. J Cell Biochem. 2011; 112: 1206-18. doi:10.1002/jcb.23042.
12. Kawada H, Fujita J, Kinjo K, Matsuzaki Y, Tsuma M, Miyatake H, et al. Nonhematopoietic mesenchymal stem cells can be mobilized and differentiate into cardiomyocytes after myocardial infarction. Blood. 2004; 104: 3581-7. doi:10.1182/blood-2004-04-1488.
13. Xu Y, Meng H, Li C, Hao M, Wang Y, Yu Z, et al. Umbilical cord-derived mesenchymal stem cells isolated by a novel explantation technique can differentiate into functional endothelial cells and promote revascularization. Stem Cells Dev. 2010; 19: 1511-22. doi:10.1089/scd.2009.0321.
14. Silva GV, Litovsky S, Assad JA, Sousa AL, Martin BJ, Vela D, et al. Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model. Circulation. 2005; 111: 150-6. doi:10.1161/01.CIR.0000151812.86142.45.
15. Ventura C, Cantoni S, Bianchi F, Lionetti V, Cavallini C, Scarlata I, et al. Hyaluronan mixed esters of butyric and retinoic Acid drive cardiac and endothelial fate in term placenta human mesenchymal stem cells and enhance cardiac repair in infarcted rat hearts. J Biol Chem. 2007; 282: 14243-52. doi: 10.1074/jbc.M609350200.
16. Kurpinski K, Lam H, Chu J, Wang A, Kim A, Tsay E, et al. Transforming growth factor-beta and notch signaling mediate stem cell differentiation into smooth muscle cells. Stem Cells. 2010; 28: 734-42. doi:10.1002/stem.319.
17. Liu J, Li W, Wang Y, Fan W, Li P, Lin W, et al. Islet-1 overexpression in human mesenchymal stem cells promotes vascularization through monocyte chemoattractant protein-3. Stem Cells. 2014; 32: 1843-54. doi:10.1002/stem.1682.
18. Dufourcq P, Descamps B, Tojais NF, Leroux L, Oses P, Daret D, et al. Secreted frizzled-related protein-1 enhances mesenchymal stem cell function in angiogenesis and contributes to neovessel maturation. Stem Cells. 2008; 26: 2991-3001. doi:10.1634/stemcells.2008-0372.
19. Suzuki S, Narita Y, Yamawaki A, Murase Y, Satake M, Mutsuga M, et al. Effects of extracellular matrix on differentiation of human bone marrow- derived mesenchymal stem cells into smooth muscle cell lineage: utility for cardiovascular tissue engineering. Cells Tissues Organs. 2010; 191: 269-80. doi: 10.1159/000260061.
20. Quevedo HC, Hatzistergos KE, Oskouei BN, Feigenbaum GS, Rodriguez JE, Valdes D, et al. Allogeneic mesenchymal stem cells restore cardiac function in chronic ischemic cardiomyopathy via trilineage differentiating capacity. Proc Natl Acad Sci U S A. 2009; 106: 14022-7. doi:10.1073/pnas.0903201106.
21. Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat Med. 2003; 9: 1195-201. doi:10.1038/nm912.
22. Tang YL, Zhao Q, Qin X, Shen L, Cheng L, Ge J, et al. Paracrine action enhances the effects of autologous mesenchymal stem cell transplantation on vascular regeneration in rat model of myocardial infarction. Ann Thorac Surg. 2005; 80: 229-36; discussion 36-7. doi:10.1016/j.athoracsur.2005.02.072.
23. Van Overstraeten-Schlogel N, Beguin Y, Gothot A. Role of stromal-derived factor-1 in the hematopoietic-supporting activity of human mesenchymal stem cells. Eur J Haematol. 2006; 76: 488-93. doi:10.1111/j.1600-0609.2006.00633.x.
24. Togel F, Hu Z, Weiss K, Isaac J, Lange C, Westenfelder C. Administered mesenchymal stem cells protect against ischemic acute renal failure through differentiation-independent mechanisms. Am J Physiol Renal Physiol. 2005; 289: F31-42. doi:10.1152/ajprenal.00007.2005.
25. Haider H, Jiang S, Idris NM, Ashraf M. IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair. Circ Res. 2008; 103: 1300-8. doi:10.1161/CIRCRESAHA.108.186742.
26. Tang J, Wang J, Guo L, Kong X, Yang J, Zheng F, et al. Mesenchymal stem cells modified with stromal cell-derived factor 1 alpha improve cardiac remodeling via paracrine activation of hepatocyte growth factor in a rat model of myocardial infarction. Mol Cells. 2010; 29: 9-19. doi:10.1007/s10059-010-0001-7.
27. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010; 4: 214-22. doi:10.1016/j.scr.2009.12.003.
28. Wen Z, Zheng S, Zhou C, Yuan W, Wang J, Wang T. Bone marrow mesenchymal stem cells for post-myocardial infarction cardiac repair: microRNAs as novel regulators. J Cell Mol Med. 2012; 16: 657-71. doi:10.1111/j.1582-4934.2011.01471.x.
29. Chen TS, Lai RC, Lee MM, Choo AB, Lee CN, Lim SK. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res. 2010; 38: 215-24. doi:10.1093/nar/gkp857.
30. Lai RC, Chen TS, Lim SK. Mesenchymal stem cell exosome: a novel stem cell-based therapy for cardiovascular disease. Regen Med. 2011; 6: 481-92. doi:10.2217/rme.11.35.
31. Jenjaroenpun P, Kremenska Y, Nair VM, Kremenskoy M, Joseph B, Kurochkin IV. Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing. PeerJ. 2013; 1: e201. doi:10.7717/peerj.201.
32. Yu X, Huang C, Song B, Xiao Y, Fang M, Feng J, et al. CD4+CD25+ regulatory T cells-derived exosomes prolonged kidney allograft survival in a rat model. Cell Immunol. 2013; 285: 62-8. doi:10.1016/j.cellimm.2013.06.010.
33. Buschow SI, van Balkom BW, Aalberts M, Heck AJ, Wauben M, Stoorvogel W. MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunol Cell Biol. 2010; 88: 851-6. doi: 10.1038/icb.2010.64.
34. Rabesandratana H, Toutant JP, Reggio H, Vidal M. Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59) are released within exosomes during In vitro maturation of reticulocytes. Blood. 1998; 91: 2573-80.
35. Al-Nedawi K, Szemraj J, Cierniewski CS. Mast cell-derived exosomes activate endothelial cells to secrete plasminogen activator inhibitor type 1. Arterioscler Thromb Vasc Biol. 2005; 25: 1744-9. doi: 10.1161/01.ATV.0000172007.86541.76.
36. Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha- granules. Blood. 1999; 94: 3791-9.
37. Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, et al. Tumor- derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med. 2001; 7: 297-303. doi:10.1038/85438.
38. Yang Y, Xiu F, Cai Z, Wang J, Wang Q, Fu Y, et al. Increased induction of antitumor response by exosomes derived from interleukin-2 gene-modified tumor cells. J Cancer Res Clin Oncol. 2007; 133: 389-99. doi:10.1007/s00432-006-0184-7.
39. Taverna S, Amodeo V, Saieva L, Russo A, Giallombardo M, De Leo G, et al. Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells. Mol Cancer. 2014; 13: 169. doi:10.1186/1476-4598-13-169.
40. Corrado C, Raimondo S, Saieva L, Flugy AM, De Leo G, Alessandro R. Exosome- mediated crosstalk between chronic myelogenous leukemia cells and human bone marrow stromal cells triggers an interleukin 8-dependent survival of leukemia cells. Cancer Lett. 2014; 348: 71-6. doi:10.1016/j.canlet.2014.03.009.
41. Yuan A, Farber EL, Rapoport AL, Tejada D, Deniskin R, Akhmedov NB, et al. Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One. 2009; 4: e4722. doi:10.1371/journal.pone.0004722.
42. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO. Exosome- mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol. 2007; 9: 654-9. doi:10.1038/ncb1596.
43. Ono M, Kosaka N, Tominaga N, Yoshioka Y, Takeshita F, Takahashi RU, et al. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci Signal. 2014; 7: ra63. doi:10.1126/scisignal.2005231.
44. Lopatina T, Bruno S, Tetta C, Kalinina N, Porta M, Camussi G. Platelet-derived growth factor regulates the secretion of extracellular vesicles by adipose mesenchymal stem cells and enhances their angiogenic potential. Cell Commun Signal. 2014; 12: 26. doi:10.1186/1478-811X-12-26.
45. Wang M, Zhao C, Shi H, Zhang B, Zhang L, Zhang X, et al. Deregulated microRNAs in gastric cancer tissue-derived mesenchymal stem cells: novel biomarkers and a mechanism for gastric cancer. Br J Cancer. 2014; 110: 1199-210. doi:10.1038/bjc.2014.14.
46. Xin H, Li Y, Cui Y, Yang JJ, Zhang ZG, Chopp M. Systemic administration of exosomes released from mesenchymal stromal cells promote functional recovery and neurovascular plasticity after stroke in rats. J Cereb Blood Flow Metab. 2013; 33: 1711-5. doi:10.1038/jcbfm.2013.152.
47. Wang J, Greene SB, Bonilla-Claudio M, Tao Y, Zhang J, Bai Y, et al. Bmp signaling regulates myocardial differentiation from cardiac progenitors through a MicroRNA-mediated mechanism. Dev Cell. 2010; 19: 903-12. doi:10.1016/j.devcel.2010.10.022.
48. Lee JK, Park SR, Jung BK, Jeon YK, Lee YS, Kim MK, et al. Exosomes derived from mesenchymal stem cells suppress angiogenesis by down-regulating VEGF expression in breast cancer cells. PLoS One. 2013; 8: e84256. doi:10.1371/journal.pone.0084256.
49. Yu B, Gong M, Wang Y, Millard RW, Pasha Z, Yang Y, et al. Cardiomyocyte protection by GATA-4 gene engineered mesenchymal stem cells is partially mediated by translocation of miR-221 in microvesicles. PLoS One. 2013; 8: e73304. doi:10.1371/journal.pone.0073304.
50. Zhang HC, Liu XB, Huang S, Bi XY, Wang HX, Xie LX, et al. Microvesicles derived from human umbilical cord mesenchymal stem cells stimulated by hypoxia promote angiogenesis both in vitro and in vivo. Stem Cells Dev. 2012; 21: 3289-97. doi:10.1089/scd.2012.0095.
51. Khubutiya MS, Vagabov AV, Temnov AA, Sklifas AN. Paracrine mechanisms of proliferative, anti-apoptotic and anti-inflammatory effects of mesenchymal stromal cells in models of acute organ injury. Cytotherapy. 2014; 16: 579-85. doi:10.1016/j.jcyt.2013.07.017.
52. Feng Y, Huang W, Wani M, Yu X, Ashraf M. Ischemic preconditioning potentiates the protective effect of stem cells through secretion of exosomes by targeting Mecp2 via miR-22. PLoS One. 2014; 9: e88685. doi:10.1371/journal.pone.0088685.
53. Follis AV, Chipuk JE, Fisher JC, Yun MK, Grace CR, Nourse A, et al. PUMA binding induces partial unfolding within BCL-xL to disrupt p53 binding and promote apoptosis. Nat Chem Biol. 2013; 9: 163-8. doi:10.1038/nchembio.1166.
54. Kim SH, Lechman ER, Bianco N, Menon R, Keravala A, Nash J, et al. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J Immunol. 2005; 174: 6440-8.
55. Kim SH, Bianco NR, Shufesky WJ, Morelli AE, Robbins PD. MHC class II+ exosomes in plasma suppress inflammation in an antigen-specific and Fas ligand/Fas-dependent manner. J Immunol. 2007; 179: 2235-41.
56. Teng H, Hu M, Yuan LX, Liu Y, Guo X, Zhang WJ, et al. Suppression of inflammation by tumor-derived exosomes: a kind of natural liposome packagedwith multifunctional proteins. J Liposome Res. 2012; 22: 346-52. doi:10.3109/08982104.2012.710911.
57. Lee C, Mitsialis SA, Aslam M, Vitali SH, Vergadi E, Konstantinou G, et al. Exosomes mediate the cytoprotective action of mesenchymal stromal cells on hypoxia-induced pulmonary hypertension. Circulation. 2012; 126: 2601-11. doi:10.1161/CIRCULATIONAHA.112.114173.
58. Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor EN, et al. Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res. 2013; 10: 301-12. doi:10.1016/j.scr.2013.01.002.
59. Haizlip KM, Janssen PM. In vitro studies of early cardiac remodeling: impact on contraction and calcium handling. Front Biosci (Schol Ed). 2011; 3: 1047-57.
60. Schuleri KH, Feigenbaum GS, Centola M, Weiss ES, Zimmet JM, Turney J, et al. Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy. Eur Heart J. 2009; 30: 2722-32. doi:10.1093/eurheartj/ehp265.
61. Tateishi K, Ashihara E, Takehara N, Nomura T, Honsho S, Nakagami T, et al. Clonally amplified cardiac stem cells are regulated by Sca-1 signaling for efficient cardiovascular regeneration. J Cell Sci. 2007; 120: 1791-800. doi:10.1242/jcs.006122.
62. Sassoli C, Pini A, Mazzanti B, Quercioli F, Nistri S, Saccardi R, et al. Mesenchymal stromal cells affect cardiomyocyte growth through juxtacrine Notch-1/Jagged-1 signaling and paracrine mechanisms: clues for cardiac regeneration. J Mol Cell Cardiol. 2011; 51: 399-408. doi:10.1016/j.yjmcc.2011.06.004.
63. Torella D, Ellison GM, Mendez-Ferrer S, Ibanez B, Nadal-Ginard B. Resident human cardiac stem cells: role in cardiac cellular homeostasis and potential for myocardial regeneration. Nat Clin Pract Cardiovasc Med. 2006; 3 Suppl 1: S8-13. doi:10.1038/ncpcardio0409.
64. Sabin K, Kikyo N. Microvesicles as mediators of tissue regeneration. Transl Res. 2014; 163: 286-95. doi:10.1016/j.trsl.2013.10.005.
65. Vrijsen KR, Sluijter JP, Schuchardt MW, van Balkom BW, Noort WA, Chamuleau SA, et al. Cardiomyocyte progenitor cell-derived exosomes stimulate migration of endothelial cells. J Cell Mol Med. 2010; 14: 1064-70. doi:10.1111/j.1582-4934.2010.01081.x.
66. Williams AR, Hatzistergos KE, Addicott B, McCall F, Carvalho D, Suncion V, et al. Enhanced effect of combining human cardiac stem cells and bone marrow mesenchymal stem cells to reduce infarct size and to restore cardiac function after myocardial infarction. Circulation. 2013; 127: 213-23. doi:10.1161/CIRCULATIONAHA.112.131110.
67. Salomon C, Ryan J, Sobrevia L, Kobayashi M, Ashman K, Mitchell M, et al. Exosomal signaling during hypoxia mediates microvascular endothelial cell migration and vasculogenesis. PLoS One. 2013; 8: e68451. doi:10.1371/journal.pone.0068451.
68. Zhu W, Huang L, Li Y, Zhang X, Gu J, Yan Y, et al. Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 2012; 315: 28-37. doi:10.1016/j.canlet.2011.10.002.
69. Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F, 3rd. Concise review: Dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells. 2011; 29: 11-9.
70. Dzau VJ, Gibbons GH. Vascular remodeling: mechanisms and implications. J Cardiovasc Pharmacol. 1993; 21 Suppl 1: S1-5.
71. Herity NA, Ward MR, Lo S, Yeung AC. Review: Clinical aspects of vascular remodeling. J Cardiovasc Electrophysiol. 1999; 10: 1016-24.
72. Xie J, Hu D, Niu L, Qu S, Wang S, Liu S. Mesenchymal stem cells attenuate vascular remodeling in monocrotaline-induced pulmonary hypertension rats. J Huazhong Univ Sci Technolog Med Sci. 2012; 32: 810-7. doi:10.1007/s11596-012-1039-x.
73. Wort SJ, Woods M, Warner TD, Evans TW, Mitchell JA. Endogenously released endothelin-1 from human pulmonary artery smooth muscle promotes cellular proliferation: relevance to pathogenesis of pulmonary hypertension and vascular remodeling. Am J Respir Cell Mol Biol. 2001; 25: 104-10. doi:10.1165/ajrcmb.25.1.4331.
74. Mao SZ, Fan XF, Xue F, Chen R, Chen XY, Yuan GS, et al. Intermedin modulates hypoxic pulmonary vascular remodeling by inhibiting pulmonary artery smooth muscle cell proliferation. Pulm Pharmacol Ther. 2014; 27: 1-9. doi:10.1016/j.pupt.2013.06.004.
75. Feld S, Kjellgren O, Smalling RW. Aggressive interventional treatment of acute myocardial infarction. Lessons from the animal laboratory applied to the catheterization suite. Cardiology. 1995; 86: 365-73.
76. Huang F, Li ML, Fang ZF, Hu XQ, Liu QM, Liu ZJ, et al. Overexpression of MicroRNA-1 improves the efficacy of mesenchymal stem cell transplantation after myocardial infarction. Cardiology. 2013; 125: 18-30. doi:10.1159/000347081.
77. Sahoo S, Losordo DW. Exosomes and cardiac repair after myocardial infarction. Circ Res. 2014; 114: 333-44. doi:10.1161/CIRCRESAHA.114.300639.
78. Cannon RO, 3rd. Mechanisms, management and future directions for reperfusion injury after acute myocardial infarction. Nat Clin Pract Cardiovasc Med. 2005; 2: 88-94. doi:10.1038/ncpcardio0096.
79. Janero DR. Therapeutic potential of vitamin E against myocardial ischemic- reperfusion injury. Free Radic Biol Med. 1991; 10: 315-24.
80. Campo GM, Squadrito F, Campo S, Altavilla D, Quartarone C, Ceccarelli S, et al. Beneficial effect of raxofelast, an hydrophilic vitamin E analogue, in the rat heart after ischemia and reperfusion injury. J Mol Cell Cardiol. 1998; 30: 1493-503. doi: 10.1006/jmcc.1998.0713.
81. Mickle DA, Weisel RD. Future directions of vitamin E and its analogues in minimizing myocardial ischemia-reperfusion injury. Can J Cardiol. 1993; 9: 89-93.
82. Tang J, Xie Q, Pan G, Wang J, Wang M. Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur J Cardiothorac Surg. 2006; 30: 353-61. doi:10.1016/j.ejcts.2006.02.070.
83. Hansmann G, Fernandez-Gonzalez A, Aslam M, Vitali SH, Martin T, Mitsialis SA, et al. Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm Circ. 2012; 2: 170-81. doi:10.4103/2045-8932.97603.
84. Baber SR, Deng W, Master RG, Bunnell BA, Taylor BK, Murthy SN, et al. Intratracheal mesenchymal stem cell administration attenuates monocrotaline- induced pulmonary hypertension and endothelial dysfunction. Am J Physiol Heart Circ Physiol. 2007; 292: H1120-8. doi:10.1152/ajpheart.00173.2006.
85. Luan Y, Zhang X, Kong F, Cheng GH, Qi TG, Zhang ZH. Mesenchymal stem cell prevention of vascular remodeling in high flow-induced pulmonary hypertension through a paracrine mechanism. Int Immunopharmacol. 2012; 14: 432-7. doi:10.1016/j.intimp.2012.08.001.
86. Jeffery TK, Morrell NW. Molecular and cellular basis of pulmonary vascular remodeling in pulmonary hypertension. Prog Cardiovasc Dis. 2002; 45: 173-202. doi:10.1053/pcad.2002.130041.
87. Mathivanan S, Ji H, Simpson RJ. Exosomes: extracellular organelles important in intercellular communication. J Proteomics. 2010; 73: 1907-20. doi:10.1016/j.jprot.2010.06.006.
88. Simons M, Raposo G. Exosomes--vesicular carriers for intercellular communication. Curr Opin Cell Biol. 2009; 21: 575-81. doi: 10.1016/j.ceb.2009.03.007.
89. Ludwig AK, Giebel B. Exosomes: small vesicles participating in intercellular communication. Int J Biochem Cell Biol. 2012; 44: 11-5. doi: 10.1016/j.biocel.2011.10.005.
90. Harding CV, Heuser JE, Stahl PD. Exosomes: looking back three decades and into the future. J Cell Biol. 2013; 200: 367-71. doi:10.1083/jcb.201212113.