Antioxidant and Anti-Inflammatory Action of Stem Cells in Cardiac Disease

Authors

  • S. Pulavendran Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, India.
  • G. Thiyagarajan Department of Biotechnology, Central Leather Research Institute, Adyar, Chennai, India.
  • V. Ramakrishnan Genetics Division, Central Research Laboratory, Chettinad University, Kelambakkam, Chennai, India.

Keywords:

Cardiomyocytes, Mesenchymal stem cells, Multipotential nonhematopoietic progenitor cells, Vascular endothelial cells

Abstract

Cardiac diseases are the consequence of blockage of blood vessels, scar formation and ultimate loss of terminally differentiated cardiomyocytes. Immune cells and oxidative stress easily slow down the cardiac functions by manipulating the cardiac tissue matrix. Stem cell-based therapies, especially mesenchymal stem cells (MSCs), multipotential nonhematopoietic progenitor cells compensate the cardiac diseases by differentiating into multiple lineages of mesenchyme including cardiomyocytes and vascular endothelial cells. Antioxidant and anti-inflammatory action of MSCs has been explored recently by various research groups. Secretion of biomolecules by MSCs perturbs and prevents the initiation, development and the function of the inflammatory cascade. These molecules mainly act through Paracrine mode. Anti-inflammatory action of MSCs mediates the cardiac diseases and the current progress in elucidating the mechanism and clinical use will be focused in detail in this article.

Downloads

Download data is not yet available.

References

Aggarwal, S. & Pittenger, M.F. (2005). Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 105(4): 1815–1822. https://doi.org/10.1182/blood-2004-04-1559.

Bao, C., Guo, J., Lin, G., Hu, M. & Hu, Z. (2008). TNFR gene-modified mesenchymal stem cells attenuate inflammation and cardiac dysfunction following MI. Scand. Cardiovasc. J., 42(1): 56–62. https://doi.org/10.1080/14017430701543556.

Bartholomew, A., Patil, S., Mackay, A., Nelson, M., Buyaner, D., Hardy, W., Mosca, J., Sturgeon, C., Siatskas, M., Mahmud, N., Ferrer, K., Deans, R., Moseley, A., Hoffman, R. & Devine, S.M. (2001). Baboon mesenchymal stem cells can be genetically modified to secrete human erythropoietin in vivo Hum. Gene Ther., 12(12): 1527–1541. https://doi.org/10.1089/10430340152480258.

Beltrami, A.P., Barlucchi, L., Torella, D., Baker, M., Limana, F., Chimenti, S., Kasahara, H., Rota, M., Musso, E., Urbanek, K., Leri, A., Kajstura, J., Nadal-Ginard, B. & Anversa, P. (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell, 114(6): 763–776. https://doi.org/10.1016/s0092-8674(03)00687-1.

Campagnoli, C., Roberts, I.A., Kumar, S., Bennett, P.R., Bellantuono, I. & Fisk, N.M. (2001). Identification of mesenchymal stem/progenitor cells in human first-trimester fetal blood, liver, and bone marrow. Blood, 98(8): 2396–2402. https://doi.org/10.1182/blood.v98.8.2396.

Caplan, A.I. & Dennis, J.E. (2006). Mesenchymal stem cells as trophic mediators. J. Cell. Biochem., 98(5): 1076–1084. https://doi.org/10.1002/jcb.20886.

De Ugarte, D.A., Morizono, K., Elbarbary, A., Alfonso, Z., Zuk, P.A., Zhu, M., Dragoo, J.L., Ashjian, P., Thomas, B., Benhaim, P., Chen, I., Fraser, J. & Hedrick, M.H. (2003). Comparison of multi-lineage cells from human adipose tissue and bone marrow. Cells Tissues Organs, 174(3): 101–109. https://doi.org/10.1159/000071150.

Dernbach, E., Urbich, C., Brandes, R.P., Hofmann, W.K., Zeiher, A.M. & Dimmeler, S. (2004). Antioxidative stress-associated genes in circulating progenitor cells: evidence for enhanced resistance against oxidative stress. Blood, 104(12): 3591–3597. https://doi.org/10.1182/blood-2003-12-4103.

Djouad, F., Charbonnier, L.M., Bouffi, C., Louis-Plence, P., Bony, C., Apparailly, F., Cantos, C., Jorgensen, C. & Noël, D. (2007). Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem cells, 25(8): 2025–2032. https://doi.org/10.1634/stemcells.2006-0548.

Erices, A., Conget, P. & Minguell, J.J. (2000). Mesenchymal progenitor cells in human umbilical cord blood. Br. J. Haematol., 109(1): 235–242. https://doi.org/10.1046/j.1365-2141.2000.01986.x.

Florini, J.R., Ewton, D.Z. & Coolican, S.A. (1996). Growth hormone and the insulin-like growth factor system in myogenesis. Endocr. Rev., 17(5): 481–517. https://doi.org/10.1210/edrv-17-5-481.

Friedenstein, A.J., Chailakhyan, R.K. & Gerasimov, U.V. (1987). Bone marrow osteogenic stem cells: in vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet., 20(3): 263–272. https://doi.org/10.1111/j.1365-2184.1987.tb01309.x.

Friedenstein, A.J., Petrakova, K.V., Kurolesova, A.I. & Frolova, G.P. (1968). Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation, 6(2): 230–247.

Friedenstein A.J. (1976). Precursor cells of mechanocytes. Int. Rev. Cytol., 47: 327–359. https://doi.org/10.1016/s0074-7696(08)60092-3.

Fuller, S.J., Mynett, J.R. & Sugden, P.H. (1992). Stimulation of cardiac protein synthesis by insulin-like growth factors. Biochem. J., 282: 85–90. https://doi.org/10.1042/bj2820085.

Gao, F., He, T., Wang, H., Yu, S., Yi, D., Liu, W. & Cai, Z. (2007). A promising strategy for the treatment of ischemic heart disease: Mesenchymal stem cell-mediated vascular endothelial growth factor gene transfer in rats. Can. J. Cardiol., 23(11): 891–898. https://doi.org/10.1016/s0828-282x(07)70845-0.

Gieseke, F., Schütt, B., Viebahn, S., Koscielniak, E., Friedrich, W., Handgretinger, R. & Müller, I. (2007). Human multipotent mesenchymal stromal cells inhibit proliferation of PBMCs independently of IFNγR1 signaling and IDO expression. Blood, 110(6): 2197–2200. https://doi.org/10.1182/blood-2007-04-083162.

Gronthos, S., Zannettino, A.C., Hay, S.J., Shi, S., Graves, S.E., Kortesidis, A. & Simmons, P.J. (2003). Molecular and cellular characterisation of highly purified stromal stem cells derived from human bone marrow. J. Cell Sci., 116: 1827–1835. https://doi.org/10.1242/jcs.00369.

He, T., Peterson, T.E., Holmuhamedov, E.L., Terzic, A., Caplice, N.M., Oberley, L.W. & Katusic, Z.S. (2004). Human endothelial progenitor cells tolerate oxidative stress due to intrinsically high expression of manganese superoxide dismutase. Arterioscler. Thromb. Vasc. Biol., 24(11): 2021–2027. https://doi.org/10.1161/01.ATV.0000142810.27849.8f.

Jackson, K.A., Majka, S.M., Wang, H., Pocius, J., Hartley, C.J., Majesky, M.W., Entman, M.L., Michael, L.H., Hirschi, K.K. & Goodell, M.A. (2001). Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells. J. Clin. Invest., 107(11): 1395–1402. https://doi.org/10.1172/JCI12150.

Jiang, X.X., Zhang, Y., Liu, B., Zhang, S.X., Wu, Y., Yu, X.D. & Mao, N. (2005). Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood, 105(10): 4120–4126. https://doi.org/10.1182/blood-2004-02-0586.

Jo, J., Nagaya, N., Miyahara, Y., Kataoka, M., Harada-Shiba, M., Kangawa, K. & Tabata, Y. (2007). Transplantation of genetically engineered mesenchymal stem cells improves cardiac function in rats with myocardial infarction: benefit of a novel nonviral vector, cationized dextran. Tissue Eng., 13(2): 313–322. https://doi.org/10.1089/ten.2006.0133.

Kaminski, K.A., Bonda, T.A., Korecki, J. & Musial, W.J. (2002). Oxidative stress and neutrophil activation--the two keystones of ischemia/reperfusion injury. Int. J. Cardiol., 86(1): 41–59. https://doi.org/10.1016/s0167-5273(02)00189-4.

Kasper, G., Mao, L., Geissler, S., Draycheva, A., Trippens, J., Kühnisch, J., Tschirschmann, M., Kaspar, K., Perka, C., Duda, G.N. & Klose, J. (2009). Insights into mesenchymal stem cell aging: involvement of antioxidant defense and actin cytoskeleton. Stem cells, 27(6): 1288–1297. https://doi.org/10.1002/stem.49.

Krampera, M., Cosmi, L., Angeli, R., Pasini, A., Liotta, F., Andreini, A., Santarlasci, V., Mazzinghi, B., Pizzolo, G., Vinante, F., Romagnani, P., Maggi, E., Romagnani, S. & Annunziato, F. (2006). Role for Interferon-γ in the Immunomodulatory Activity of Human Bone Marrow Mesenchymal Stem Cells. Stem cells, 24(2): 386–398. https://doi.org/10.1634/stemcells.2005-0008.

Libby, P., Ridker, P.M. & Maseri, A. (2002). Inflammation and atherosclerosis. Circulation, 105(9): 1135–1143. https://doi.org/10.1161/hc0902.104353.

Lodie, T.A., Blickarz, C.E., Devarakonda, T.J., He, C., Dash, A.B., Clarke, J., Gleneck, K., Shihabuddin, L. & Tubo, R. (2002). Systematic analysis of reportedly distinct populations of multipotent bone marrow-derived stem cells reveals a lack of distinction. Tissue Eng., 8(5): 739–751. https://doi.org/10.1089/10763270260424105.

Maby-El Hajjami, H., Amé-Thomas, P., Pangault, C., Tribut, O., DeVos, J., Jean, R., Bescher, N., Monvoisin, C., Dulong, J., Lamy, T., Fest, T. & Tarte, K. (2009). Functional alteration of the lymphoma stromal cell niche by the cytokine context: role of indoleamine-2,3 dioxygenase. Cancer Res., 69(7): 3228–3237. https://doi.org/10.1158/0008-5472.CAN-08-3000.

Mangi, A.A., Noiseux, N., Kong, D., He, H., Rezvani, M., Ingwall, J.S. & Dzau, V.J. (2003). Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts. Nat. Med., 9(9): 1195–1201. https://doi.org/10.1038/nm912.

Meisel, R., Zibert, A., Laryea, M., Göbel, U., Däubener, W. & Dilloo, D. (2004). Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. Blood, 103(12): 4619–4621. https://doi.org/10.1182/blood-2003-11-3909.

Messina, E., De Angelis, L., Frati, G., Morrone, S., Chimenti, S., Fiordaliso, F., Salio, M., Battaglia, M., Latronico, M.V., Coletta, M., Vivarelli, E., Frati, L., Cossu, G. & Giacomello, A. (2004). Isolation and expansion of adult cardiac stem cells from human and murine heart. Circ. Res., 95(9): 911–921. https://doi.org/10.1161/01.RES.0000147315.71699.51.

Nakamura, T., Mizuno, S., Matsumoto, K., Sawa, Y., Matsuda, H. & Nakamura, T. (2000). Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF. J. Clin. Invest., 106(12): 1511–1519. https://doi.org/10.1172/JCI10226.

Németh, K., Leelahavanichkul, A., Yuen, P.S., Mayer, B., Parmelee, A., Doi, K., Robey, P.G., Leelahavanichkul, K., Koller, B.H., Brown, J.M., Hu, X., Jelinek, I., Star, R.A. & Mezey, E. (2009). Bone marrow stromal cells attenuate sepsis via prostaglandin E(2)-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat. Med., 15(1): 42–49. https://doi.org/10.1038/nm.1905.

Nishikimi, T., Yoshihara, F., Horinaka, S., Kobayashi, N., Mori, Y., Tadokoro, K., Akimoto, K., Minamino, N., Kangawa, K. & Matsuoka, H. (2003). Chronic administration of adrenomedullin attenuates transition from left ventricular hypertrophy to heart failure in rats. Hypertension, 42(5): 1034–1041. https://doi.org/10.1161/01.HYP.0000097604.64716.D2.

Noiseux, N., Gnecchi, M., Lopez-Ilasaca, M., Zhang, L., Solomon, S.D., Deb, A., Dzau, V.J. & Pratt, R.E. (2006). Mesenchymal stem cells overexpressing Akt dramatically repair infarcted myocardium and improve cardiac function despite infrequent cellular fusion or differentiation. Mol. Ther., 14(6): 840–850. https://doi.org/10.1016/j.ymthe.2006.05.016.

Noort, W.A., Kruisselbrink, A.B., in't Anker, P.S., Kruger, M., van Bezooijen, R.L., de Paus, R.A., Heemskerk, M.H., Löwik, C.W., Falkenburg, J.H., Willemze, R. & Fibbe, W.E. (2002). Mesenchymal stem cells promote engraftment of human umbilical cord blood–derived CD34+ cells in NOD/SCID mice. Exp. Hematol., 30(8): 870–878. https://doi.org/10.1016/s0301-472x(02)00820-2.

Nuttall, S.L., Kendall, M.J. & Martin, U. (1999). Antioxidant therapy for the prevention of cardiovascular disease. QJM, 92(5): 239–244. https://doi.org/10.1093/qjmed/92.5.239.

Oh, H., Bradfute, S.B., Gallardo, T.D., Nakamura, T., Gaussin, V., Mishina, Y., Pocius, J., Michael, L.H., Behringer, R.R., Garry, D.J., Entman, M.L. & Schneider, M.D. (2003). Cardiac progenitor cells from adult myocardium: homing, differentiation, and fusion after infarction. Proc. Natl. Acad. Sci. USA, 100(21): 12313–12318. https://doi.org/10.1073/pnas.2132126100.

Okumura, H., Nagaya, N., Itoh, T., Okano, I., Hino, J., Mori, K., Tsukamoto, Y., Ishibashi-Ueda, H., Miwa, S., Tambara, K., Toyokuni, S., Yutani, C. & Kangawa, K. (2004). Adrenomedullin infusion attenuates myocardial ischemia/reperfusion injury through the phosphatidylinositol 3-kinase/Akt-dependent pathway. Circulation, 109(2): 242–248. https://doi.org/10.1161/01.CIR.0000109214.30211.7C.

Ono, I., Yamashita, T., Hida, T., Jin, H.Y., Ito, Y., Hamada, H., Akasaka, Y., Ishii, T. & Jimbow, K. (2004). Local administration of hepatocyte growth factor gene enhances the regeneration of dermis in acute incisional wounds. J. Surg. Res., 120(1): 47–55. https://doi.org/10.1016/j.jss.2003.08.242.

Opitz, C.A., Litzenburger, U.M., Lutz, C., Lanz, T.V., Tritschler, I., Köppel, A., Tolosa, E., Hoberg, M., Anderl, J., Aicher, W.K., Weller, M., Wick, W. & Platten, M. (2009). Toll-Like Receptor Engagement Enhances the Immunosuppressive Properties of Human Bone Marrow-Derived Mesenchymal Stem Cells by Inducing Indoleamine-2,3-dioxygenase-1 via Interferon-β and Protein Kinase R. Stem cells, 27(4): 909–919. https://doi.org/10.1002/stem.7.

Orlic, D., Kajstura, J., Chimenti, S., Jakoniuk, I., Anderson, S.M., Li, B., Pickel, J., McKay, R., Nadal-Ginard, B., Bodine, D.M., Leri, A. & Anversa, P. (2001). Bone marrow cells regenerate infarcted myocardium. Nature, 410: 701–705. https://doi.org/10.1038/35070587.

Owen, M. & Friedenstein, A.J. (1988). Stromal stem cells: marrow-derived osteogenic precursors. Ciba Found. Symp., 136: 42–60. https://doi.org/10.1002/9780470513637.ch4.

Pittenger, M.F., Mackay, A.M., Beck, S.C., Jaiswal, R.K., Douglas, R., Mosca, J.D., Moorman, M.A., Simonetti, D.W., Craig, S. & Marshak, D.R. (1999). Multilineage potential of adult human mesenchymal stem cells. Science, 284: 143–147. https://doi.org/10.1126/science.284.5411.143.

Polchert, D., Sobinsky, J., Douglas, G., Kidd, M., Moadsiri, A., Reina, E., Genrich, K., Mehrotra, S., Setty, S., Smith, B. & Bartholomew, A. (2008). IFN-γ activation of mesenchymal stem cells for treatment and prevention of graft versus host disease. Eur. J. Immunol., 38(6): 1745–1755. https://doi.org/10.1002/eji.200738129.

Prashant, A.V., Harishchandra, H., D'Souza, V. & D'Souza, B. (2007). Age related changes in lipid peroxidation and antioxidants in elderly people. Indian J. Clin. Biochem., 22(1): 131–134. https://doi.org/10.1007/BF02912896.

Raffaghello, L., Bianchi, G., Bertolotto, M., Montecucco, F., Busca, A., Dallegri, F., Ottonello, L. & Pistoia, V. (2008). Human mesenchymal stem cells inhibit neutrophil apoptosis: a model for neutrophil preservation in the bone marrow niche. Stem cells, 26(1): 151–162. https://doi.org/10.1634/stemcells.2007-0416.

Rafii, S. & Lyden, D. (2003). Therapeutic stem and progenitor cell transplantation for organ vascularization and regeneration. Nat. Med., 9: 702–712. https://doi.org/10.1038/nm0603-702.

Rauscher, F.M., Goldschmidt-Clermont, P.J., Davis, B.H., Wang, T., Gregg, D., Ramaswami, P., Pippen, A.M., Annex, B.H., Dong, C. & Taylor, D.A. (2003). Aging, progenitor cell exhaustion, and atherosclerosis. Circulation, 108(4): 457–463. https://doi.org/10.1161/01.CIR.0000082924.75945.48.

Ren, G., Su, J., Zhang, L., Zhao, X., Ling, W., L'huillie, A., Zhang, J., Lu, Y., Roberts, A.I., Ji, W., Zhang, H., Rabson, A.B. & Shi, Y. (2009). Species variation in the mechanisms of mesenchymal stem cell-mediated immunosuppression. Stem cells, 27(8): 1954–1962. https://doi.org/10.1002/stem.118.

Ren, G., Zhang, L., Zhao, X., Xu, G., Zhang, Y., Roberts, A.I., Zhao, R.C. & Shi, Y. (2008). Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell, 2(2): 141–150. https://doi.org/10.1016/j.stem.2007.11.014.

Ryan, J.M., Barry, F., Murphy, J.M. & Mahon, B.P. (2007). Interferon-γ does not break, but promotes the immunosuppressive capacity of adult human mesenchymal stem cells. Clin. Exp. Immunol., 149(2): 353–363. https://doi.org/10.1111/j.1365-2249.2007.03422.x.

Sato, K., Ozaki, K., Oh, I., Meguro, A., Hatanaka, K., Nagai, T., Muroi, K. & Ozawa, K. (2007). Nitric oxide plays a critical role in suppression of T-cell proliferation by mesenchymal stem cells. Blood, 109(1): 228–234. https://doi.org/10.1182/blood-2006-02-002246.

Sethe, S., Scutt, A. & Stolzing, A. (2006). Aging of mesenchymal stem cells. Ageing Res. Rev., 5(1): 91–116. https://doi.org/10.1016/j.arr.2005.10.001.

Sharpless, N.E. & DePinho, R.A. (2007). How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol., 8: 703–713. https://doi.org/10.1038/nrm2241.

Song, H., Kwon, K., Lim, S., Kang, S.M., Ko, Y.G., Xu, Z., Chung, J.H., Kim, B.S., Lee, H., Joung, B., Park, S., Choi, D., Jang, Y., Chung, N.S., Yoo, K.J. & Hwang, K.C. (2005). Transfection of mesenchymal stem cells with the FGF-2 gene improves their survival under hypoxic conditions. Mol. Cells, 19(3): 402–407.

Spaggiari, G.M., Abdelrazik, H., Becchetti, F. & Moretta, L. (2009). MSCs inhibit monocyte-derived DC maturation and function by selectively interfering with the generation of immature DCs: central role of MSC-derived prostaglandin E2. Blood, 113(26): 6576–6583. https://doi.org/10.1182/blood-2009-02-203943.

Sun, J., Li, S.H., Liu, S.M., Wu, J., Weisel, R.D., Zhuo, Y.F., Yau, T.M., Li, R.K. & Fazel, S.S. (2009). Improvement in cardiac function after bone marrow cell thearpy is associated with an increase in myocardial inflammation. Am. J. Physiol. Heart Circ. Physiol., 296(1): H43–H50. https://doi.org/10.1152/ajpheart.00613.2008.

Tang, Y.L., Tang, Y., Zhang, Y.C., Qian, K., Shen, L. & Phillips, M.I. (2005). Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J. Am. Coll. Cardiol., 46(7): 1339–1350. https://doi.org/10.1016/j.jacc.2005.05.079.

Tang, Y.L., Zhao, Q., Zhang, Y.C., Cheng, L., Liu, M., Shi, J., Yang, Y.Z., Pan, C., Ge, J. & Phillips, M.I. (2004). Autologous mesenchymal stem cell transplantation induce VEGF and neovascularization in ischemic myocardium. Regul. Pept., 117(1): 3–10. https://doi.org/10.1016/j.regpep.2003.09.005.

Tsuruda, T., Kato, J., Kitamura, K., Kawamoto, M., Kuwasako, K., Imamura, T., Koiwaya, Y., Tsuji, T., Kangawa, K. & Eto, T. (1999). An autocrine or a paracrine role of adrenomedullin in modulating cardiac fibroblast growth. Cardiovasc. Res., 43(4): 958–967. https://doi.org/10.1016/s0008-6363(99)00122-4.

Urish, K.L., Vella, J.B., Okada, M., Deasy, B.M., Tobita, K., Keller, B.B., Cao, B., Piganelli, J.D. & Huard, J. (2009). Antioxidant levels represent a major determinant in the regenerative capacity of muscle stem cells. Mol. Biol. Cell., 20(1): 509–520. https://doi.org/10.1091/mbc.e08-03-0274.

Yoon, Y.S., Wecker, A., Heyd, L., Park, J.S., Tkebuchava, T., Kusano, K., Hanley, A., Scadova, H., Qin, G., Cha, D.H., Johnson, K.L., Aikawa, R., Asahara, T. & Losordo, D.W. (2005). Clonally expanded novel multipotent stem cells from human bone marrow regenerate myocardium after myocardial infarction. J. Clin. Invest., 115(2): 326–338. https://doi.org/10.1172/JCI22326.

Downloads

Abstract views: 24 / PDF downloads: 10

Published

2010-10-01

How to Cite

Pulavendran, S., Thiyagarajan, G., & Ramakrishnan, V. (2010). Antioxidant and Anti-Inflammatory Action of Stem Cells in Cardiac Disease. Advances in BioScience, 1(2), 71–78. Retrieved from https://journals.sospublication.co.in/ab/article/view/27

Issue

Section

Articles