Interleukin-10 Delivery via Mesenchymal Stem Cells: A Novel Gene Therapy Approach to Prevent Lung Ischemia–Reperfusion Injury
Abstract
Ischemia–reperfusion (IR) injury is an important cause of primary graft failure in lung transplantation. In this study, viral interleukin-10 (vIL-10)-engineered mesenchymal stem cells (MSCs) were tested for their ability to prevent lung IR injury. Bone marrow-derived MSCs were transduced with rvIL-10-retrovirus. After 120 min of warm left lung ischemia, rats received ∼15 × 106 vIL-10-engineered MSCs (MSC-vIL-10), empty vector-engineered MSCs (MSC-vec), or saline intravenously. Mean blood oxygenation (PaO2/FiO2 ratio, mmHg) was measured at 4 hr, 24 hr, 72 hr, and 7 days. As early as 4 hr post-IR injury with MSC-vIL-10 treatment, blood oxygenation was significantly (p < 0.05) improved (319 ± 94; n = 7) compared with untreated (saline) controls (63 ± 19; n = 6). At 24 hr post-IR injury, in the MSC-vIL-10-treated group there was a further increase in blood oxygenation (353 ± 105; n = 10) compared with the MSC-vec group (138 ± 86; n = 9) and saline group (87 ± 39; n = 10). By 72 hr, oxygenation reached normal (475 ± 55; n = 9) in the MSC-vIL-10-treated group but not in the saline-treated and MSC-vec-treated groups. At 4 hr after IR injury, lungs with MSC-vIL10 treatment had a lower (p < 0.05) injury score (0.9 ± 0.4) compared with lungs of the untreated (saline) group (2.5 ± 1.4) or MSC-vec-treated group (2 ± 0.4). Lung microvascular permeability and wet-to-dry weight ratios were markedly lower in the MSC-vIL10 group compared with untreated (saline) controls. ISOL (in situ oligonucleotide ligation for DNA fragmentation detection) and caspase-3 staining demonstrated significantly (p < 0.05) fewer apoptotic cells in MSC-vIL10-treated lungs. Animals that received MSC-vIL10 therapy had fewer (p < 0.05) CD4+ and CD8+ T cells in bronchoalveolar lavage fluid compared with untreated control animals. A therapeutic strategy using vIL-10-engineered MSCs to prevent IR injury in lung transplantation seems promising.
Get full access to this article
View all available purchase options and get full access to this article.
References
Allay J.A.Dennis J.E.Haynesworth S.E.Majumdar M.K.Clapp D.W.Shultz L.D.Caplan A.I.Gerson S.L.1997. LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitorsHum. Gene Ther.81417-1427. Allay, J.A., Dennis, J.E., Haynesworth, S.E., Majumdar, M.K., Clapp, D.W., Shultz, L.D., Caplan, A.I., and Gerson, S.L. (1997). LacZ and interleukin-3 expression in vivo after retroviral transduction of marrow-derived human osteogenic mesenchymal progenitors. Hum. Gene Ther. 8, 1417–1427.
Apparailly F.Verwaerde C.Jacquet C.Auriault C.Sany J.Jorgensen C.1998. Adenovirus-mediated transfer of viral IL-10 gene inhibits murine collagen-induced arthritisJ. Immunol.1605213-5220. Apparailly, F., Verwaerde, C., Jacquet, C., Auriault, C., Sany, J., and Jorgensen, C. (1998). Adenovirus-mediated transfer of viral IL-10 gene inhibits murine collagen-induced arthritis. J. Immunol. 160, 5213–5220.
Bando K.Paradis I.L.Similo S.Konishi H.Komatsu K.Zullo T.G.Yousem S.A.Close J.M.Zeevi A.Duquesnoy R.J.1995. Obliterative bronchiolitis after lung and heart–lung transplantation: An analysis of risk factors and managementJ. Thorac. Cardiovasc. Surg.1104-13. Bando, K., Paradis, I.L., Similo, S., Konishi, H., Komatsu, K., Zullo, T.G., Yousem, S.A., Close, J.M., Zeevi, A., and Duquesnoy, R.J. (1995). Obliterative bronchiolitis after lung and heart–lung transplantation: An analysis of risk factors and management. J. Thorac. Cardiovasc. Surg. 110, 4–13.
Bianco P.Robey P.G.2001. Stem cells in tissue engineeringNature414118-121. Bianco, P. and Robey, P.G. (2001). Stem cells in tissue engineering. Nature 414, 118–121.
Boehler A.Estenne M.2003. Post-transplant bronchiolitis obliteransEur. Respir. J.221007-1018. Boehler, A., and Estenne, M. (2003). Post-transplant bronchiolitis obliterans. Eur. Respir. J. 22, 1007–1018.
Caplan A.2008. Why are MSCs therapeutic?New data: New insight. J. Pathol.217318-324. Caplan, A. (2008). Why are MSCs therapeutic? New data: New insight. J. Pathol. 217, 318–324.
Choi J.J.Yoo S.A.Park S.J.Kang Y.J.Kim W.U.Oh I.H.Cho C.S.2008. Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in miceClin. Exp. Immunol.153269-276. Choi, J.J., Yoo, S.A., Park, S.J., Kang, Y.J., Kim, W.U., Oh, I.H., and Cho, C.S. (2008). Mesenchymal stem cells overexpressing interleukin-10 attenuate collagen-induced arthritis in mice. Clin. Exp. Immunol. 153, 269–276.
Christie J.D.van Raemdonck D.De Perrot M.Barr M.Keshavjee S.Arcasoy S.Orens J.ISHLT Working Group on Primary Lung Graft Dysfunction2005a. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction. I. Introduction and methodsJ. Heart Lung Transplant241451-1453. Christie, J.D., van Raemdonck, D., De Perrot, M., Barr, M., Keshavjee, S., Arcasoy, S., and Orens, J.; ISHLT Working Group on Primary Lung Graft Dysfunction. (2005a). Report of the ISHLT Working Group on Primary Lung Graft Dysfunction. I. Introduction and methods. J. Heart Lung Transplant. 24, 1451–1453.
Christie J.D.Carby M.Bag R.Corris P.Hertz M.Weill D.ISHLT Working Group on Primary Lung Graft Dysfunction2005b. Report of the ISHLT Working Group on Primary Lung Graft Dysfunction. II. Definition. A consensus statement of the International Society for Heart and Lung TransplantationJ. Heart Lung Transplant241454-1459. Christie, J.D., Carby, M., Bag, R., Corris, P., Hertz, M., and Weill, D.; ISHLT Working Group on Primary Lung Graft Dysfunction. (2005b). Report of the ISHLT Working Group on Primary Lung Graft Dysfunction. II. Definition. A consensus statement of the International Society for Heart and Lung Transplantation. J. Heart Lung Transplant. 24, 1454–1459.
Christie J.D.Edwards L.B.Aurora P.Dobbels F.Kirk R.Rahmel A.O.Taylor D.O.Kucheryavaya A.Y.Hertz M.I.2008. Registry of the International Society for Heart and Lung Transplantation: Twenty-fifth official adult lung and heart/lung transplantation report—2008J. Heart Lung Transplant.27957-969. Christie, J.D., Edwards, L.B., Aurora, P., Dobbels, F., Kirk, R., Rahmel, A.O., Taylor, D.O., Kucheryavaya, A.Y., and Hertz, M.I. (2008). Registry of the International Society for Heart and Lung Transplantation: Twenty-fifth official adult lung and heart/lung transplantation report—2008. J. Heart Lung Transplant. 27, 957–969.
Colligan J.E.Kruisbeek A.M.Margulies D.H.Shevach E.M.Strober W.1994Coico R.Current Protocols in ImmunologyJohn Wiley & SonsNew York14.1.4. Colligan, J.E., Kruisbeek, A.M., Margulies, D.H., Shevach, E.M., and Strober, W. (1994). Coico, R., ed. Current Protocols in Immunology (John Wiley & Sons, New York) pp. 14.1.4.
David A.Chetritt J.Guillot C.Tesson L.Heslan J.M.Cuturi M.C.Soulillou J.P.Anegon I.2000. Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in ratsGene Ther.7505-510. David, A., Chetritt, J., Guillot, C., Tesson, L., Heslan, J.M., Cuturi, M.C., Soulillou, J.P., and Anegon, I. (2000). Interleukin-10 produced by recombinant adenovirus prolongs survival of cardiac allografts in rats. Gene Ther. 7, 505–510.
Deans R.J.Moseley A.B.2000. Mesenchymal stem cells: Biology and potential clinical usesExp. Hematol.28875-884. Deans, R.J., and Moseley, A.B. (2000). Mesenchymal stem cells: Biology and potential clinical uses. Exp. Hematol. 28, 875–884.
Deng W.Han Q.Liao L.Li C.Ge W.Zhao Z.You S.Deng H.Zhao R.C.2004. Allogeneic bone marrow-derived flk-1+Sca-1− mesenchymal stem cells leads to stable mixed chimerism and donor-specific toleranceExp. Hematol.32861-867. Deng, W., Han, Q., Liao, L., Li, C., Ge, W., Zhao, Z., You, S., Deng, H., and Zhao, R.C. (2004). Allogeneic bone marrow-derived flk-1+Sca-1− mesenchymal stem cells leads to stable mixed chimerism and donor-specific tolerance. Exp. Hematol. 32, 861–867.
De Perrot M.Liu M.Waddell T.K.Keshavjee S.2003a. Ischemia–reperfusion induced lung injuryAm. J. Respir. Crit. Care Med.167490-511. De Perrot, M., Liu, M., Waddell, T.K., AND Keshavjee, S. (2003a). Ischemia–reperfusion induced lung injury. Am. J. Respir. Crit. Care Med. 167, 490–511.
De Perrot M.Young K.Imai Y.Liu M.Waddell T.K.Fischer S.Zhang L.Keshavjee S.2003b. Recipient T cells mediate reperfusion injury after lung transplantation in the ratJ. Immunol.1714995-5002. De Perrot, M., Young, K., Imai, Y., Liu, M., Waddell, T.K., Fischer, S., Zhang, L., and Keshavjee, S. (2003b). Recipient T cells mediate reperfusion injury after lung transplantation in the rat. J. Immunol. 171, 4995–5002.
Devine S.M.Bartholomew A.M.Mahmud N.Nelson M.Patil S.Hardy W.Sturgeon C.Hewett T.Chung T.Stock W.Sher D.Weissman S.Ferrer K.Mosca J.Deans R.Moseley A.Hoffman R.2001. Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusionExp. Hematol.29244-255. Devine, S.M., Bartholomew, A.M., Mahmud, N., Nelson, M., Patil, S., Hardy, W., Sturgeon, C., Hewett, T., Chung, T., Stock, W., Sher, D., Weissman, S., Ferrer, K., Mosca, J., Deans, R., Moseley, A., and Hoffman, R. (2001). Mesenchymal stem cells are capable of homing to the bone marrow of non-human primates following systemic infusion. Exp. Hematol. 29, 244–255.
De Waal Malefyt R.Abrams J.Bennett B.Figdor C.G.De Vries J.E.1991. Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytesJ. Exp. Med.1741209-1220. De Waal Malefyt, R., Abrams, J., Bennett, B., Figdor, C.G., and De Vries, J.E. (1991). Interleukin 10 (IL-10) inhibits cytokine synthesis by human monocytes: An autoregulatory role of IL-10 produced by monocytes. J. Exp. Med. 174, 1209–1220.
Djouad F.Plence P.Bony C.Tropel P.Apparailly F.Sany J.Noel D.Jorgensen C.2003. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animalsBlood1023837-3844. Djouad, F., Plence, P., Bony, C., Tropel, P., Apparailly, F., Sany, J., Noel, D., and Jorgensen, C. (2003). Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 102, 3837–3844.
Dowdall J.F.Winter D.C.Bouchier-Hayes D.J.2002. Ionosine modulates gut barrier dysfunction and end organ damage in a model of ischemia–reperfusion injuryJ. Surg. Res.10861-68. Dowdall, J.F., Winter, D.C., and Bouchier-Hayes, D.J. (2002). Ionosine modulates gut barrier dysfunction and end organ damage in a model of ischemia–reperfusion injury. J. Surg. Res. 108, 61–68.
Ellman P.I.Reece B.T.Law M.G.Gazoni M.L.Singh R.Laubach V.E.Linden J.Tribble C.G.Kron I.L.2008. Adenosine A2A activation attenuates nontransplantation lung reperfusion injuryJ. Surg. Res.1493-8. Ellman, P.I., Reece, B.T., Law, M.G., Gazoni, M.L., Singh, R., Laubach, V.E., Linden, J., Tribble, C.G., and Kron, I.L. (2008). Adenosine A2A activation attenuates nontransplantation lung reperfusion injury. J. Surg. Res. 149, 3–8.
Eppinger M.J.Deeb G.M.Bolling S.F.Ward P.A.1997. Mediators of ischemia–reperfusion injury of rat lungAm. J. Pathol.1501773-1784. Eppinger, M.J., Deeb, G.M., Bolling, S.F., and Ward, P.A. (1997). Mediators of ischemia–reperfusion injury of rat lung. Am. J. Pathol. 150, 1773–1784.
Erdogan M.Kalaycioglu S.Iriz E.2005. Protective effect of aprotinin against lung damage in patients undergoing CABG surgeryActa Cardiol.60367-372. Erdogan, M., Kalaycioglu, S., Iriz, E. (2005) Protective effect of aprotinin against lung damage in patients undergoing CABG surgery. Acta Cardiol. 60, 367–372.
Fiorentino D.F.Zlotnik A.Vieira P.Mosmann T.R.Howard M.Moore K.W.O'Garra A.1991a. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cellsJ. Immunol.1463444-3451. Fiorentino, D.F., Zlotnik, A., Vieira, P., Mosmann, T.R., Howard, M., Moore, K.W., and O'Garra, A. (1991a). IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J. Immunol. 146, 3444–3451.
Fiorentino D.F.Zlotnik A.Mosmann T.R.Howard M.O'Garra A.1991b. IL-10 inhibits cytokine production by activated macrophagesJ. Immunol.1473815-3822. Fiorentino, D.F., Zlotnik, A., Mosmann, T.R., Howard, M., and O'Garra, A. (1991b). IL-10 inhibits cytokine production by activated macrophages. J. Immunol. 147, 3815–3822.
Fischer S.Keshavjee S.2001. Apoptosis in lung transplantationGraft4481-490. Fischer, S., and Keshavjee, S. (2001). Apoptosis in lung transplantation. Graft 4, 481–490.
Fischer S.Cassivi S.D.Xavier A.M.Cardella J.A.Cutz E.Edwards V.Liu M.Keshavjee S.2000. Cell death in human lung transplantation: Apoptosis induction in human lungs during ischemia and after transplantationAnn. Surg.231424-431. Fischer, S., Cassivi, S.D., Xavier, A.M., Cardella, J.A., Cutz, E., Edwards, V., Liu, M., and Keshavjee, S. (2000). Cell death in human lung transplantation: Apoptosis induction in human lungs during ischemia and after transplantation. Ann. Surg. 231, 424–431.
Fischer S.Liu M.Maclean A.A.De Perrot M.Ho M.Cardella J.A.Zhang X.M.Bai X.H.Suga M.Imai Y.Keshavjee S.2001. In vivo transtracheal adenoviral mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia–reperfusion injury and improves early post-transplant graft function in the ratHum. Gene Ther.121513-1526. Fischer, S., Liu, M., Maclean, A.A., De Perrot, M., Ho, M., Cardella, J.A., Zhang, X.M., Bai, X.H., Suga, M., Imai, Y., and Keshavjee, S. (2001). In vivo transtracheal adenoviral mediated transfer of human interleukin-10 gene to donor lungs ameliorates ischemia–reperfusion injury and improves early post-transplant graft function in the rat. Hum. Gene Ther. 12, 1513–1526.
Fischer S.De Perrot M.Liu M.Maclean A.A.Cardella J.A.Imai Y.Suga M.Keshavjee S.2003. Interleukin 10 gene transfection of donor lungs ameliorates post-transplant cell death by a switch from cellular necrosis to apoptosisJ. Thorac. Cardiovasc. Surg.1261174-1180. Fischer, S., De Perrot, M., Liu, M., Maclean, A.A., Cardella, J.A., Imai, Y., Suga, M., and Keshavjee, S. (2003). Interleukin 10 gene transfection of donor lungs ameliorates post-transplant cell death by a switch from cellular necrosis to apoptosis. J. Thorac. Cardiovasc. Surg. 126, 1174–1180.
Fiser S.M.Tribble C.G.Long S.M.Kaza A.K.Kern J.A.Jones D.R.Robbins M.K.Kron I.L.2002. Ischemia–reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndromeAnn. Thorac. Surg.731041-1047. Fiser, S.M., Tribble, C.G., Long, S.M., Kaza, A.K., Kern, J.A., Jones, D.R., Robbins, M.K., Kron, I.L. (2002). Ischemia–reperfusion injury after lung transplantation increases risk of late bronchiolitis obliterans syndrome. Ann. Thorac. Surg. 73, 1041–1047.
Geudens N.Vanaudenaerde B.M.Neyrinck A.P.van de Wauwer C.Vos R.Verleden G.M.Verbeken E.Lerut T.van Raemdonck D.E.2007. The importance of lymphocytges in lung ischemia–reperfusion injuryTransplant. Proc.392659-2662. Geudens, N., Vanaudenaerde, B.M., Neyrinck, A.P., van de Wauwer, C., Vos, R., Verleden, G.M., Verbeken, E., Lerut, T., and van Raemdonck, D.E. (2007). The importance of lymphocytges in lung ischemia–reperfusion injury. Transplant. Proc. 39, 2659–2662.
Hamada H.Kobune M.Nakamura K.Kawano Y.Kato K.Honmou O.Houkin K.Matsunaga T.Niitsu Y.2005. Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapyCancer Sci.96149-156. Hamada, H., Kobune, M., Nakamura, K., Kawano, Y., Kato, K., Honmou, O., Houkin, K., Matsunaga, T., and Niitsu, Y. (2005). Mesenchymal stem cells (MSC) as therapeutic cytoreagents for gene therapy. Cancer Sci. 96, 149–156.
Harrington K.Alvarez-Vallina L.Crittenden M.Gough M.Chong H.Diaz R.M.Vassaux G.Lemoine N.Vile R.2002. Cells as vehicles for cancer gene therapy: The missing link between targeted vectors and systemic delivery?Hum. Gene Ther.131263-1280. Harrington, K., Alvarez-Vallina, L., Crittenden, M., Gough, M., Chong, H., Diaz, R.M., Vassaux, G., Lemoine, N., and Vile, R. (2002). Cells as vehicles for cancer gene therapy: The missing link between targeted vectors and systemic delivery? Hum. Gene Ther. 13, 1263–1280.
Haydock D.A.Trulock E.P.Kaiser L.R.Knight S.R.Pasque M.K.Cooper J.D.1992. Management of dysfunction in the transplanted lung: Experience with 7 clinical casesAnn. Thorac. Surg.53635-641. Haydock, D.A., Trulock, E.P., Kaiser, L.R., Knight, S.R., Pasque, M.K., and Cooper, J.D. (1992). Management of dysfunction in the transplanted lung: Experience with 7 clinical cases. Ann. Thorac. Surg. 53, 635–641.
Hosenpud J.D.Bennett L.E.Keck B.M.Boucek M.M.Novick R.J.2000. The Registry of the International Society for Heart and Lung Transplantation: Seventeenth official report—2000J. Heart Lung Transplant.19909-931. Hosenpud, J.D., Bennett, L.E., Keck, B.M., Boucek, M.M., and Novick, R.J. (2000). The Registry of the International Society for Heart and Lung Transplantation: Seventeenth official report—2000. J. Heart Lung Transplant. 19, 909–931.
Hsu D.H.De Waal-Malefyt R.Fiorentino D.F.Dang M.N.Vieira P.De Vries J.E.Spits H.Mosmann T.R.Moore K.W.1990. Expression of IL-10 activity by Epstein-Barr virus protein BCRF1Science250830-832. Hsu, D.H., De Waal-Malefyt, R., Fiorentino, D.F., Dang, M.N., Vieira, P., De Vries, J.E., Spits, H., Mosmann, T.R. and Moore, K.W. (1990). Expression of IL-10 activity by Epstein-Barr virus protein BCRF1. Science 250, 830–832.
Iglesias J.L.Lanoue J.L.Rogers T.E.Inman L.Turnage R.H.1998. Physiologic basis of pulmonary edema during intestinal reperfusionJ. Surg. Res.80156-163. Iglesias, J.L., Lanoue, J.L., Rogers, T.E., Inman, L., and Turnage, R.H. (1998). Physiologic basis of pulmonary edema during intestinal reperfusion. J. Surg. Res. 80, 156–163.
Jander S.Kraemer M.Schroeter M.Witte O.W.Stoll G.1995. Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortexJ. Cereb. Blood Flow Metab.1542-51. Jander, S., Kraemer, M., Schroeter, M., Witte, O.W., and Stoll, G. (1995). Lymphocytic infiltration and expression of intercellular adhesion molecule-1 in photochemically induced ischemia of the rat cortex. J. Cereb. Blood Flow Metab. 15, 42–51.
Jiang Y.Jahagirdar B.N.Reinhardt R.L.Schwartz R.E.Keene C.D.Ortiz-Gonzalez X.R.Reyes M.Lenvik T.Lund T.Blackstad M.Du J.Aldrich S.Lisberg A.Low W.C.Largaespada D.A.Verfaillie C.M.2002. Pluripotency of mesenchymal stem cells derived from adult marrowNature41841-49. Jiang, Y., Jahagirdar, B.N., Reinhardt, R.L., Schwartz, R.E., Keene, C.D., Ortiz-Gonzalez, X.R., Reyes, M., Lenvik, T., Lund, T., Blackstad, M., Du, J., Aldrich, S., Lisberg, A., Low, W.C., Largaespada, D.A., and Verfaillie, C.M. (2002). Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 418, 41–49.
Jordan S.Mitchell J.A.Quinlan G.J.Goldstraw P.Evans T.W.2000. The pathogenesis of lung injury following pulmonary resectionEur. Respir. J.15790. Jordan, S., Mitchell, J.A., Quinlan, G.J., Goldstraw, P., and Evans, T.W. (2000). The pathogenesis of lung injury following pulmonary resection. Eur. Respir. J. 15, 790.
Jorgensen C.Djouad F.Apparailly F.Noel D.2003. Engineering mesenchymal stem cells for immunotherapyGene Ther.10928-931. Jorgensen, C., Djouad, F., Apparailly, F., and Noel, D. (2003). Engineering mesenchymal stem cells for immunotherapy. Gene Ther. 10, 928–931.
Kabay B.Aytekin F.O.Aydin C.Ozer A.Kabay N.Tekin K.Sungurtekin U.Erdem E.Ozden A.2005. Interleukin-10 gene therapy attenuates pulmonary tissue injury caused by mesenteric ischemia–reperfusion in a mouse modelTohoku J. Exp. Med.207133-142. Kabay, B., Aytekin, F.O., Aydin, C., Ozer, A., Kabay, N., Tekin, K., Sungurtekin, U., Erdem, E., and Ozden, A. (2005). Interleukin-10 gene therapy attenuates pulmonary tissue injury caused by mesenteric ischemia–reperfusion in a mouse model. Tohoku J. Exp. Med. 207, 133–142.
Kabay B.Teke Z.Aytekin F.O.Yenisey C.Bir F.Sacar M.Erdem E.Ozden A.2007. Pyrrolidine dithiocarbamate reduces lung injury caused by mesenteric ischemia/reperfusion in a rat modelWorld J. Surg.311707-1715. Kabay, B., Teke, Z., Aytekin, F.O., Yenisey, C., Bir, F., Sacar, M., Erdem, E., and Ozden, A. (2007). Pyrrolidine dithiocarbamate reduces lung injury caused by mesenteric ischemia/reperfusion in a rat model. World J. Surg. 31, 1707–1715.
King R.C.Binns O.A.Rodriguez F.Kanithanon R.C.Daniel T.M.Spotnitz W.D.Tribble C.G.Kron I.L.2000. Reperfusion injury significantly impacts clinical outcome after pulmonary transplantationAnn. Thorac. Surg.691681. King, R.C., Binns, O.A., Rodriguez, F., Kanithanon, R.C., Daniel, T.M., Spotnitz, W.D., Tribble, C.G., and Kron, I.L. (2000). Reperfusion injury significantly impacts clinical outcome after pulmonary transplantation. Ann. Thorac. Surg. 69, 1681.
Koike K.Yamamoto Y.Hori Y.Ono T.2000. Group II phospholipase A2 mediates lung injury in intestinal ischemia–reperfusionAnn. Surg.23290-97. Koike, K., Yamamoto, Y., Hori, Y., and Ono, T. (2000). Group II phospholipase A2 mediates lung injury in intestinal ischemia–reperfusion. Ann. Surg. 232, 90–97.
Koksoy C.Kuzu M.A.Ergun H.Demirpence E.Zulfikaroglu B.2000. Intestinal ischemia and reperfusion impairs vasomotor functions of pulmonary vascular bedAnn. Surg.231105-111. Koksoy, C., Kuzu, M.A., Ergun, H., Demirpence, E., and Zulfikaroglu, B. (2000). Intestinal ischemia and reperfusion impairs vasomotor functions of pulmonary vascular bed. Ann. Surg. 231, 105–111.
Koksoy C.Kuzu M.A.Kuzu I.Ergun H.Gurhan I.2001. Role of tumor necrosis factor in lung injury caused by intestinal ischemia–reperfusionBr. J. Surg.88464-468. Koksoy, C., Kuzu, M.A., Kuzu, I., Ergun, H., and Gurhan, I. (2001). Role of tumor necrosis factor in lung injury caused by intestinal ischemia–reperfusion. Br. J. Surg. 88, 464–468.
Kotton D.N.Ma B.Y.Cardoso W.V.Sanderson E.A.Summer R.S.Williams M.C.Fine A.2001. Bone marrow-derived cells as progenitors of lung alveolar epitheliumDevelopment1285181-5188. Kotton, D.N., Ma, B.Y., Cardoso, W.V., Sanderson, E.A., Summer, R.S., Williams, M.C., and Fine, A. (2001). Bone marrow-derived cells as progenitors of lung alveolar epithelium. Development 128, 5181–5188.
Kozower B.D.Kanaan S.A.Tagawa T.Suda T.Grapperhaus K.Daddi N.Crouch E.C.Doerschuk C.M.Patterson G.A.2002. Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia–reperfusion injuryAm. J. Transplant.2837-842. Kozower, B.D., Kanaan, S.A., Tagawa, T., Suda, T., Grapperhaus, K., Daddi, N., Crouch, E.C., Doerschuk, C.M., and Patterson, G.A. (2002). Intramuscular gene transfer of interleukin-10 reduces neutrophil recruitment and ameliorates lung graft ischemia–reperfusion injury. Am. J. Transplant. 2, 837–842.
Kuzu M.A.Koksoy C.Kuzu I.Gurhan I.Ergun H.Demirpence E.2002. Role of integrins and intracellular adhesion molecule-1 in lung injury after intestinal ischemia–reperfusionAm. J. Surg.18370-74. Kuzu, M.A., Koksoy, C., Kuzu, I., Gurhan, I., Ergun, H., and Demirpence, E. (2002). Role of integrins and intracellular adhesion molecule-1 in lung injury after intestinal ischemia–reperfusion. Am. J. Surg. 183, 70–74.
Lau C.L.Patterson G.A.Palmer S.M.2004. Critical care aspects of lung transplantationJ. Intensive Care Med.1983-104. Lau, C.L., Patterson, G.A., AND Palmer, S.M. (2004). Critical care aspects of lung transplantation. J. Intensive Care Med. 19, 83–104.
Linfert D.Chowdhry T.Rabb H.2009. Lymphocytes and ischemia–reperfusion injuryTransplantation Rev.231-10. Linfert, D., Chowdhry, T., and Rabb, H. (2009). Lymphocytes and ischemia–reperfusion injury. Transplantation Rev. 23, 1–10.
Ma Y.Thornton S.Duwel L.E.Boivin G.P.Giannini E.H.Leiden J.M.Bluestone J.A.Hirsch R.1998. Inhibition of collagen-induced arthritis in mice by viral IL-10 gene transferJ. Immunol.1611516-1524. Ma, Y., Thornton, S., Duwel, L.E., Boivin, G.P., Giannini, E.H., Leiden, J.M., Bluestone, J.A., Hirsch, R. (1998). Inhibition of collagen-induced arthritis in mice by viral IL-10 gene transfer. J. Immunol. 161, 1516–1524.
Majno G.Joris I.1995. Apoptosis, oncosis, and necrosis: An overview of cell deathAm. J. Pathol.1463-15. Majno, G., and Joris, I. (1995). Apoptosis, oncosis, and necrosis: An overview of cell death. Am. J. Pathol. 146, 3–15.
Miller A.D.1996. Cell-surface receptors for retroviruses and implication for gene transferProc. Natl. Acad. Sci. U.S.A.9311407-11413. Miller, A.D. (1996). Cell-surface receptors for retroviruses and implication for gene transfer. Proc. Natl. Acad. Sci. U.S.A. 93, 11407–11413.
Miller D.G.Miller A.D.1994. A family of retroviruses that utilize related phosphate transporters for cell entryJ. Virol.688270-8276. Miller, D.G., and Miller, A.D. (1994). A family of retroviruses that utilize related phosphate transporters for cell entry. J. Virol. 68, 8270–8276.
Mohanty J.G.Jaffe J.S.Schulman E.S.Raible D.G.1997. A highly sensitive fluorescent micro-assay of H2O2 release from activated human leukocytes using a dihydroxyphenoxazine derivativeJ. Immunol. Methods202133-141. Mohanty, J.G., Jaffe, J.S., Schulman, E.S., and Raible, D.G. (1997). A highly sensitive fluorescent micro-assay of H2O2 release from activated human leukocytes using a dihydroxyphenoxazine derivative. J. Immunol. Methods 202, 133–141.
Moore K.W.Vieira P.Fiorentino D.F.Trounstine M.L.Khan T.A.Mosmann T.R.1990. Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFIScience2481230-1234. Moore, K.W., Vieira, P., Fiorentino, D.F., Trounstine, M.L., Khan, T.A., and Mosmann, T.R. (1990). Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science 248, 1230–1234.
Nagaya N.Fujii T.Iwase T.Ohgushi H.Itoh T.Uematsu M.Yamagishi M.Mori H.Kangawa K.Kitamura S2004. Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesisAm. J. Physiol. Heart Circ. Physiol.287H2670-H2676. Nagaya, N., Fujii, T., Iwase, T., Ohgushi, H., Itoh, T., Uematsu, M., Yamagishi, M., Mori, H., Kangawa, K., and Kitamura S. (2004). Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am. J. Physiol. Heart Circ. Physiol. 287, H2670–H2676.
Neuss S.Becher E.Woltje M.Tietze L.Jahnen-Dechent W.2004. Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healingStem Cells22405-414. Neuss, S., Becher, E., Woltje, M., Tietze, L., and Jahnen-Dechent, W. (2004). Functional expression of HGF and HGF receptor/c-met in adult human mesenchymal stem cells suggests a role in cell mobilization, tissue repair, and wound healing. Stem Cells 22, 405–414.
Ng C.S.Wan S.Yim A.P.Arifi A.A.2002. Pulmonary dysfunction after cardiac surgeryChest1211269. Ng, C.S., Wan, S., Yim, A.P., and Arifi, A.A. (2002). Pulmonary dysfunction after cardiac surgery. Chest 121, 1269.
Okazaki M.Kreisel F.Richardson S.B.Kreisel D.Krupnick A.S.Patterson G.A.Gelman A.E.2007. Sphingosine 1-phosphate inhibits ischemia reperfusion injury following experimental lung transplantationAm. J. Transplant.7751-758. Okazaki, M., Kreisel, F., Richardson, S.B., Kreisel, D., Krupnick, A.S., Patterson, G.A., and Gelman, A.E. (2007). Sphingosine 1-phosphate inhibits ischemia reperfusion injury following experimental lung transplantation. Am. J. Transplant. 7, 751–758.
Oswald J.Boxberger S.Jorgensen B.Feldmann S.Ehninger G.Bornhauser M.Werner C.2004. Mesenchymal stem cells can be differentiated into endothelial cells in vitroStem Cells22377-384. Oswald, J., Boxberger, S., Jorgensen, B., Feldmann, S., Ehninger, G., Bornhauser, M., and Werner, C. (2004). Mesenchymal stem cells can be differentiated into endothelial cells in vitro. Stem Cells 22, 377–384.
Patel S.A.Sherman L.Munoz J.Rameshwar P.2008. Immunological properties of mesenchymal stem cells and clinical implicationsArch. Immunol. Ther. Exp.561-8. Patel, S.A., Sherman, L., Munoz, J., and Rameshwar, P. (2008). Immunological properties of mesenchymal stem cells and clinical implications. Arch. Immunol. Ther. Exp. 56, 1–8.
Pennline K.J.Roque-Gaffney E.Monahan M.1994. Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouseClin. Immunol. Immunopathol.71169-175. Pennline, K.J., Roque-Gaffney, E., and Monahan, M. (1994). Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse. Clin. Immunol. Immunopathol. 71, 169–175.
Plumas J.Chaperot L.Richard M.J.Molens J.P.Bensa J.C.Favrot M.C.2005. Mesenchymal stem cells induce apoptosis of activated T cellsLeukemia191597-1604. Plumas, J., Chaperot, L., Richard, M.J., Molens, J.P., Bensa, J.C., and Favrot, M.C. (2005). Mesenchymal stem cells induce apoptosis of activated T cells. Leukemia 19, 1597–1604.
Porhanov V.A.Poliakov I.S.Selvaschuk A.P.Grechishkin A.I.Sitnik S.D.Nikolaev I.F.Efimtsev J.P.Marchenko L.G.2002. Indications and results of sleeve carinal resectionEur. J. Cardiothorac. Surg.22685-694. Porhanov, V.A., Poliakov, I.S., Selvaschuk, A.P., Grechishkin, A.I., Sitnik, S.D., Nikolaev, I.F., Efimtsev, J.P., and Marchenko, L.G. (2002). Indications and results of sleeve carinal resection. Eur. J. Cardiothorac. Surg. 22, 685–694.
Prockop D.J.2003. Further proof of the plasticity of adult stem cells and their role in tissue repairJ. Cell Biol.160807-809. Prockop, D.J. (2003). Further proof of the plasticity of adult stem cells and their role in tissue repair. J. Cell Biol. 160, 807–809.
Qin L.Chavin K.D.Ding Y.Tahara H.Favaro J.P.Woodward J.E.Suzuki T.Robbins P.D.Lotze M.TBromberg J.S.1996. Retrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survivalJ. Immunol.1562316-2323. Qin, L., Chavin, K.D., Ding, Y., Tahara, H., Favaro, J.P., Woodward, J.E., Suzuki, T., Robbins, P.D., Lotze M.T., and Bromberg, J.S. (1996). Retrovirus-mediated transfer of viral IL-10 gene prolongs murine cardiac allograft survival. J. Immunol. 156, 2316–2323.
Rezai N.Podor T.J.McManus B.M.2004. Bone marrow cells in the repair and modulation of Herat and blood vessels: Emerging opportunities in native and engineered tissue and biomechanical materialsArtif. Organs28142-151. Rezai, N., Podor, T.J., and McManus, B.M. (2004). Bone marrow cells in the repair and modulation of Herat and blood vessels: Emerging opportunities in native and engineered tissue and biomechanical materials. Artif. Organs 28, 142–151.
Ross S.D.Tribble C.G.Gaughen J.R.Shockey K.S.Parrino P.E.Kron I.L.1999. Reduced neutrophil infiltration protects against lung reperfusion injury after transplantationAnn. Thorac. Surg.671428-1433. Ross, S.D., Tribble, C.G., Gaughen, J.R., Shockey, K.S., Parrino, P.E., and Kron, I.L. (1999). Reduced neutrophil infiltration protects against lung reperfusion injury after transplantation. Ann. Thorac. Surg. 67, 1428–1433.
Saito T.Kuang J.Q.Bittira B.Al-Khald A.Chiu R.C.2002. Xenotransplant cardiac chimera: Immune tolerance of adult stem cellsAnn. Thorac. Surg.7419-24. Saito, T., Kuang, J.Q., Bittira, B., Al-Khald, A., and Chiu, R.C. (2002). Xenotransplant cardiac chimera: Immune tolerance of adult stem cells. Ann. Thorac. Surg. 74, 19–24.
Salgar S.K.Yang D.Ruiz P.Miller J.Tzakis A.2004. Viral interleukin-10 engineered autologous hematopoietic stem cell therapy: A novel gene therapy approach to prevent graft rejectionHum. Gene Ther.15131-144. Salgar, S.K., Yang, D., Ruiz, P., Miller, J., and Tzakis, A. (2004). Viral interleukin-10 engineered autologous hematopoietic stem cell therapy: A novel gene therapy approach to prevent graft rejection. Hum. Gene Ther. 15, 131–144.
Schroeter M.Jander S.Witte O.W.Stoll G.1994. Local immune response in the rat cerebral cortex after middle cerebral artery occlusionJ. Neuroimmunol.55195-203. Schroeter, M., Jander, S., Witte, O.W., and Stoll, G. (1994). Local immune response in the rat cerebral cortex after middle cerebral artery occlusion. J. Neuroimmunol. 55, 195–203.
Semedo P.Wang P.MAndreucci T.H.Cenedeze M.A.Teixeira V.P.Reis M.A.Pacheco-Silva A.Câmara N.O.2007. Mesenchymal stem cells ameliorate tissue damages triggered by renal ischemia and reperfusion injuryTransplant. Proc.39421-423. Semedo, P., Wang, P.M, Andreucci, T.H., Cenedeze, M.A., Teixeira, V.P., Reis, M.A., Pacheco-Silva, A., and Câmara, N.O. (2007). Mesenchymal stem cells ameliorate tissue damages triggered by renal ischemia and reperfusion injury. Transplant. Proc. 39, 421–423.
Sharples L.D.McNeil K.Stewart S.Wallwork J.2002. Risk factors for bronchiolitis obliterans: A systematic review of recent publicationsJ. Heart Lung Transplant.21271-281. Sharples, L.D., McNeil, K., Stewart, S., and Wallwork, J. (2002). Risk factors for bronchiolitis obliterans: A systematic review of recent publications. J. Heart Lung Transplant. 21, 271–281.
Snell G.IEsmore D.SWilliams T.J.1996. Cytolytic therapy for the bronchiolitis obliterans syndrome complicating lung transplantationChest109874-878. Snell, G.I, Esmore, D.S, and Williams, T.J. (1996). Cytolytic therapy for the bronchiolitis obliterans syndrome complicating lung transplantation. Chest 109, 874–878.
Stagg J.2007. Immune regulation by mesenchymal stem cells: Two sides to the coinTissue Antigens691-9. Stagg, J. (2007). Immune regulation by mesenchymal stem cells: Two sides to the coin. Tissue Antigens 69, 1–9.
Taga K.Tosato G.1992. IL-10 inhibits human T cell proliferation and IL-2 productionJ. Immunol.1481143-1148. Taga, K., and Tosato, G. (1992). IL-10 inhibits human T cell proliferation and IL-2 production. J. Immunol. 148, 1143–1148.
Tang J.Xie Q.Pan G.Wang J.Wang M.2006. Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusionEur. J. Cardiothorac. Surg.30353-361. Tang, J., Xie, Q., Pan, G., Wang, J., and Wang, M. (2006). Mesenchymal stem cells participate in angiogenesis and improve heart function in rat model of myocardial ischemia with reperfusion. Eur. J. Cardiothorac. Surg. 30, 353–361.
Thompson-Snipes L.Dhar V.Bond M.W.Mosmann T.R.Moore K.W.Rennick D.M.1991. Interleukin 10: A novel stimulatory factor for mast cells and their progenitorsJ. Exp. Med.173507-510. Thompson-Snipes, L., Dhar, V., Bond, M.W., Mosmann, T.R., Moore, K.W., and Rennick, D.M. (1991). Interleukin 10: A novel stimulatory factor for mast cells and their progenitors. J. Exp. Med. 173, 507–510.
Togel F.Weiss K.Yang Y.Hu Z.Zhang P.Westenfelder C.2007. Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injuryAm. J. Physiol. Renal Physiol.292F1626-F1635. Togel, F., Weiss, K., Yang, Y., Hu, Z., Zhang, P., and Westenfelder, C. (2007). Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am. J. Physiol. Renal Physiol. 292, F1626–F1635.
Tse W.T.Pendleton J.D.Beyer W.M.Egalka M.C.Guinan E.C.2003. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantationTransplantation75389-397. Tse, W.T., Pendleton, J.D., Beyer, W.M., Egalka, M.C., and Guinan, E.C. (2003). Suppression of allogeneic T-cell proliferation by human marrow stromal cells: Implications in transplantation. Transplantation 75, 389–397.
van der Kaaij N.P.Haitsma J.J.Kluin J.Lambrecht B.N.Lachmann B.De Bruin R.W.Bogers A.J.2005. Surfactant pretreatment ameliorates ischemia–reperfusion injury of the lungEur. J. Cardiothorac. Surg.27774-782. van der Kaaij, N.P., Haitsma, J.J., Kluin, J., Lambrecht, B.N., Lachmann, B., De Bruin, R.W., and Bogers, A.J. (2005). Surfactant pretreatment ameliorates ischemia–reperfusion injury of the lung. Eur. J. Cardiothorac. Surg. 27, 774–782.
Vieira P.De Waal-Malefyt R.Dang M.N.Johnson K.E.Kastelein R.Fiorentino D.F.Devries J.E.Roncarolo M.G.Mosmann T.R.Moore K.W.1991. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: Homology to Epstein–Barr virus open reading frame BCRFIProc. Natl. Acad. Sci. U.S.A.881172-1176. Vieira, P., De Waal-Malefyt, R., Dang, M.N., Johnson, K.E., Kastelein, R., Fiorentino, D.F., Devries, J.E., Roncarolo, M.G., Mosmann, T.R., and Moore, K.W. (1991). Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: Homology to Epstein–Barr virus open reading frame BCRFI. Proc. Natl. Acad. Sci. U.S.A. 88, 1172–1176.
Vollweiler J.L.Zielske S.P.Reese J.S.Gerson S.L.2003. Hematopoietic stem cell gene therapy: Progress toward therapeutic targetsBone Marrow Transplant.321-7. Vollweiler, J.L., Zielske, S.P., Reese, J.S., and Gerson, S.L. (2003). Hematopoietic stem cell gene therapy: Progress toward therapeutic targets. Bone Marrow Transplant. 32, 1–7.
Williams E.A.Evans T.W.Goldstraw P.1996. Acute lung injury following lung resection: Is one lung anaesthesia to blame?Thorax51114-116. Williams, E.A., Evans, T.W., and Goldstraw, P. (1996). Acute lung injury following lung resection: Is one lung anaesthesia to blame? Thorax 51, 114–116.
Wilson W.C.Laborde P.R.Benumof J.L.Taylor R.Swetland J.F.1993. Reperfusion injury and exhaled hydrogen peroxideAnesth. Analg.77963-970. Wilson, W.C., Laborde, P.R., Benumof, J.L., Taylor, R., and Swetland, J.F. (1993). Reperfusion injury and exhaled hydrogen peroxide. Anesth. Analg. 77, 963–970.
Yang Z.Day Y.J.Toufektsian M.C.Xu Y.Ramos S.I.Marshall M.A.French B.A.Linden J.2006. Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytesCirculation1142056-2064. Yang, Z., Day, Y.J., Toufektsian, M.C., Xu, Y., Ramos, S.I., Marshall, M.A., French, B.A., and Linden, J. (2006). Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytes. Circulation 114, 2056–2064.
Yilmaz G.Arumugam T.V.Strokes K.Y.Granger D.N.2006. Role of T lymphocytes and interferon-γ in ischemic strokeCirculation1132105-2112. Yilmaz, G., Arumugam, T.V., Strokes, K.Y., and Granger, D.N. (2006). Role of T lymphocytes and interferon-γ in ischemic stroke. Circulation 113, 2105–2112.
Zhang Y.C.Pileggi A.Agarwal A.Molano R.D.Powers M.Brusko T.Wasserfall C.Goudy K.Zahr E.Poggioli R.Scott-Jorgensen M.Campbell-Thompson M.Crawford J.M.Nick H.Flotte T.Ellis T.M.Ricordi C.Inverardi L.Atkinson M.A.2003. Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD miceDiabetes52708-716. Zhang, Y.C., Pileggi, A., Agarwal, A., Molano, R.D., Powers, M., Brusko, T., Wasserfall, C., Goudy, K., Zahr, E., Poggioli, R., Scott-Jorgensen, M., Campbell-Thompson, M., Crawford, J.M., Nick, H., Flotte, T., Ellis, T.M., Ricordi, C., Inverardi, L., and Atkinson, M.A. (2003). Adeno-associated virus-mediated IL-10 gene therapy inhibits diabetes recurrence in syngeneic islet cell transplantation of NOD mice. Diabetes 52, 708–716.
Zhou M.Diwu Z.Panchuk-Voloshina N.Haugland R.P.1997. A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: Applications in detecting the activity of phagocyte NADPH oxidase and other oxidasesAnal. Biochem.253162-168. Zhou, M., Diwu, Z., Panchuk-Voloshina, N., and Haugland, R.P. (1997). A stable nonfluorescent derivative of resorufin for the fluorometric determination of trace hydrogen peroxide: Applications in detecting the activity of phagocyte NADPH oxidase and other oxidases. Anal. Biochem. 253, 162–168.
Information & Authors
Information
Published In
Copyright
Copyright 2010, Mary Ann Liebert, Inc.
History
Published in print: June 2010
Published ahead of print: 4 May 2010
Published online: 28 April 2010
Published ahead of production: 26 January 2010
Accepted: 26 January 2010
Received: 10 August 2009
Topics
Authors
Author Disclosure Statement
For all authors of this report, no competing financial interests exist.
Metrics & Citations
Metrics
Citations
Export Citation
Export citation
Select the format you want to export the citations of this publication.
View Options
Get Access
Access content
To read the fulltext, please use one of the options below to sign in or purchase access.⚠ Society Access
If you are a member of a society that has access to this content please log in via your society website and then return to this publication.