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Journal of Immunology Research
Volume 2015, Article ID 391797, 14 pages
http://dx.doi.org/10.1155/2015/391797
Review Article

Safety and Efficacy Endpoints for Mesenchymal Stromal Cell Therapy in Renal Transplant Recipients

1Department of Nephrology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands
2Department of Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, Netherlands

Received 28 April 2015; Accepted 26 May 2015

Academic Editor: Bjarne K. Møller

Copyright © 2015 J. R. Bank et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. K. E. Lamb, S. Lodhi, and H.-U. Meier-Kriesche, “Long-term renal allograft survival in the United States: a critical reappraisal,” American Journal of Transplantation, vol. 11, no. 3, pp. 450–462, 2011. View at Publisher · View at Google Scholar · View at Scopus
  2. B. J. Nankivell, R. J. Borrows, C. L.-S. Fung, P. J. O'Connell, R. D. M. Allen, and J. R. Chapman, “The natural history of chronic allograft nephropathy,” The New England Journal of Medicine, vol. 349, no. 24, pp. 2326–2333, 2003. View at Publisher · View at Google Scholar · View at Scopus
  3. H. Amer and M. D. Griffin, “Modulating kidney transplant interstitial fibrosis and tubular atrophy: is the RAAS an important target?” Kidney International, vol. 85, no. 2, pp. 240–243, 2014. View at Publisher · View at Google Scholar · View at Scopus
  4. F. Casiraghi, N. Perico, and G. Remuzzi, “Mesenchymal stromal cells to promote solid organ transplantation tolerance,” Current Opinion in Organ Transplantation, vol. 18, no. 1, pp. 51–58, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. A. Bartholomew, C. Sturgeon, M. Siatskas et al., “Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo,” Experimental Hematology, vol. 30, no. 1, pp. 42–48, 2002. View at Publisher · View at Google Scholar · View at Scopus
  6. H. P. Zhou, D. H. Yi, S. Q. Yu et al., “Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft,” Transplantation Proceedings, vol. 38, no. 9, pp. 3046–3051, 2006. View at Publisher · View at Google Scholar · View at Scopus
  7. F. Casiraghi, N. Azzollini, P. Cassis et al., “Pretransplant infusion of mesenchymal stem cells prolongs the survival of a semiallogeneic heart transplant through the generation of regulatory T cells,” The Journal of Immunology, vol. 181, no. 6, pp. 3933–3946, 2008. View at Publisher · View at Google Scholar · View at Scopus
  8. M. de Martino, S. Zonta, T. Rampino et al., “Mesenchymal stem cells infusion prevents acute cellular rejection in rat kidney transplantation,” Transplantation Proceedings, vol. 42, no. 4, pp. 1331–1335, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. W. Zhang, C. Qin, and Z. M. Zhou, “Mesenchymal stem cells modulate immune responses combined with cyclosporine in a rat renal transplantation model,” Transplantation Proceedings, vol. 39, no. 10, pp. 3404–3408, 2007. View at Publisher · View at Google Scholar · View at Scopus
  10. S. Alagesan and M. D. Griffin, “Autologous and allogeneic mesenchymal stem cells in organ transplantation: what do we know about their safety and efficacy?” Current Opinion in Organ Transplantation, vol. 19, no. 1, pp. 65–72, 2014. View at Publisher · View at Google Scholar · View at Scopus
  11. M. E. Reinders, J. R. Bank, G. J. Dreyer et al., “Autologous bone marrow derived mesenchymal stromal cell therapy in combination with everolimus to preserve renal structure and function in renal transplant recipients,” Journal of Translational Medicine, vol. 12, article 331, 2014. View at Publisher · View at Google Scholar
  12. N. Perico, F. Casiraghi, M. Introna et al., “Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility,” Clinical Journal of the American Society of Nephrology, vol. 6, no. 2, pp. 412–422, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. N. Perico, F. Casiraghi, E. Gotti et al., “Mesenchymal stromal cells and kidney transplantation: pretransplant infusion protects from graft dysfunction while fostering immunoregulation,” Transplant International, vol. 26, no. 9, pp. 867–878, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. M. E. J. Reinders, J. W. de Fijter, H. Roelofs et al., “Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study,” Stem Cells Translational Medicine, vol. 2, no. 2, pp. 107–111, 2013. View at Publisher · View at Google Scholar · View at Scopus
  15. Y. Peng, M. Ke, L. Xu et al., “Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study,” Transplantation, vol. 95, no. 1, pp. 161–168, 2013. View at Publisher · View at Google Scholar · View at Scopus
  16. H. Lee, J. B. Park, S. Lee, S. Baek, H. Kim, and S. J. Kim, “Intra-osseous injection of donor mesenchymal stem cell (MSC) into the bone marrow in living donor kidney transplantation; a pilot study,” Journal of Translational Medicine, vol. 11, no. 1, article 96, 2013. View at Publisher · View at Google Scholar · View at Scopus
  17. C. Mudrabettu, V. Kumar, A. Rakha et al., “Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: a pilot study,” Nephrology, vol. 20, no. 1, pp. 25–33, 2015. View at Publisher · View at Google Scholar
  18. J. Tan, W. Wu, X. Xu et al., “Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial,” The Journal of the American Medical Association, vol. 307, no. 11, pp. 1169–1177, 2012. View at Publisher · View at Google Scholar · View at Scopus
  19. S. Hariharan, M. A. McBride, and E. P. Cohen, “Evolution of endpoints for renal transplant outcome,” American Journal of Transplantation, vol. 3, no. 8, pp. 933–941, 2003. View at Publisher · View at Google Scholar · View at Scopus
  20. P. A. Lachenbruch, A. S. Rosenberg, E. Bonvini, M. W. Cavaillé-Coll, and R. B. Colvin, “Biomarkers and surrogate endpoints in renal transplantation: present status and considerations for clinical trial design,” American Journal of Transplantation, vol. 4, no. 4, pp. 451–457, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. K. English, A. French, and K. J. Wood, “Mesenchymal stromal cells: facilitators of successful transplantation?” Cell Stem Cell, vol. 7, no. 4, pp. 431–442, 2010. View at Publisher · View at Google Scholar · View at Scopus
  22. M. E. Bernardo and W. E. Fibbe, “Mesenchymal stromal cells: sensors and switchers of inflammation,” Cell Stem Cell, vol. 13, no. 4, pp. 392–402, 2013. View at Publisher · View at Google Scholar · View at Scopus
  23. M. M. Duffy, T. Ritter, R. Ceredig, and M. D. Griffin, “Mesenchymal stem cell effects on T-cell effector pathways,” Stem Cell Research & Therapy, vol. 2, no. 4, article 34, 2011. View at Publisher · View at Google Scholar · View at Scopus
  24. M. di Nicola, C. Carlo-Stella, M. Magni et al., “Human bone marrow stromal cells suppress T-lymphocyte proliferation induced by cellular or nonspecific mitogenic stimuli,” Blood, vol. 99, no. 10, pp. 3838–3843, 2002. View at Publisher · View at Google Scholar · View at Scopus
  25. R. Meisel, A. Zibert, M. Laryea, U. Göbel, W. Däubener, and D. Dilloo, “Human bone marrow stromal cells inhibit allogeneic T-cell responses by indoleamine 2,3-dioxygenase-mediated tryptophan degradation,” Blood, vol. 103, no. 12, pp. 4619–4621, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. M. Krampera, S. Glennie, J. Dyson et al., “Bone marrow mesenchymal stem cells inhibit the response of naive and memory antigen-specific T cells to their cognate peptide,” Blood, vol. 101, no. 9, pp. 3722–3729, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. S. Glennie, I. Soeiro, P. J. Dyson, E. W.-F. Lam, and F. Dazzi, “Bone marrow mesenchymal stem cells induce division arrest anergy of activated T cells,” Blood, vol. 105, no. 7, pp. 2821–2827, 2005. View at Publisher · View at Google Scholar · View at Scopus
  28. A. J. Nauta, A. B. Kruisselbrink, E. Lurvink, R. Willemze, and W. E. Fibbe, “Mesenchymal stem cells inhibit generation and function of both CD34+-derived and monocyte-derived dendritic cells,” Journal of Immunology, vol. 177, no. 4, pp. 2080–2087, 2006. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Ghannam, J. Pene, G. Torcy-Moquet, C. Jorgensen, and H. Yssel, “Mesenchymal stem cells inhibit human Th17 cell differentiation and function and induce a T regulatory cell phenotype,” Journal of Immunology, vol. 185, pp. 302–312, 2010. View at Publisher · View at Google Scholar
  30. R. Tatara, K. Ozaki, Y. Kikuchi et al., “Mesenchymal stromal cells inhibit Th17 but not regulatory T-cell differentiation,” Cytotherapy, vol. 13, no. 6, pp. 686–694, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. S. Aggarwal and M. F. Pittenger, “Human mesenchymal stem cells modulate allogeneic immune cell responses,” Blood, vol. 105, no. 4, pp. 1815–1822, 2005. View at Publisher · View at Google Scholar · View at Scopus
  32. G. M. Spaggiari, A. Capobianco, H. Abdelrazik, F. Becchetti, M. C. Mingari, and L. Moretta, “Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2,” Blood, vol. 111, no. 3, pp. 1327–1333, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. G. M. Spaggiari, A. Capobianco, S. Becchetti, M. C. Mingari, and L. Moretta, “Mesenchymal stem cell-natural killer cell interactions: evidence that activated NK cells are capable of killing MSCs, whereas MSCs can inhibit IL-2-induced NK-cell proliferation,” Blood, vol. 107, no. 4, pp. 1484–1490, 2006. View at Publisher · View at Google Scholar · View at Scopus
  34. P. A. Sotiropoulou, S. A. Perez, A. D. Gritzapis, C. N. Baxevanis, and M. Papamichail, “Interactions between human mesenchymal stem cells and natural killer cells,” Stem Cells, vol. 24, no. 1, pp. 74–85, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. X. X. Jiang, Y. Zhang, B. Liu et al., “Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells,” Blood, vol. 105, no. 10, pp. 4120–4126, 2005. View at Publisher · View at Google Scholar · View at Scopus
  36. W. Zhang, W. Ge, C. Li et al., “Effects of mesenchymal stem cells on differentiation, maturation, and function of human monocyte-derived dendritic cells,” Stem Cells and Development, vol. 13, no. 3, pp. 263–271, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Chiesa, S. Morbelli, S. Morando et al., “Mesenchymal stem cells impair in vivo T-cell priming by dendritic cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 42, pp. 17384–17389, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. K. English, J. M. Ryan, L. Tobin, M. J. Murphy, F. P. Barry, and B. P. Mahon, “Cell contact, prostaglandin E2 and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25Highforkhead box P3+ regulatory T cells,” Clinical and Experimental Immunology, vol. 156, no. 1, pp. 149–160, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. S. Tabera, J. A. Pérez-Simón, M. Díez-Campelo et al., “The effect of mesenchymal stem cells on the viability, proliferation and differentiation of B-lymphocytes,” Haematologica, vol. 93, no. 9, pp. 1301–1309, 2008. View at Publisher · View at Google Scholar · View at Scopus
  40. Y. Peng, X. Chen, Q. Liu et al., “Mesenchymal stromal cells infusions improve refractory chronic graft versus host disease through an increase of CD5+ regulatory B cells producing interleukin 10,” Leukemia, vol. 29, no. 3, pp. 636–646, 2014. View at Publisher · View at Google Scholar
  41. M. Franquesa, F. K. Mensah, R. Huizinga et al., “Human adipose tissue-derived mesenchymal stem cells abrogate plasmablast formation and induce regulatory B cells independently of T helper cells,” Stem Cells, vol. 33, no. 3, pp. 880–891, 2015. View at Publisher · View at Google Scholar
  42. F. Casiraghi, N. Azzollini, M. Todeschini et al., “Localization of mesenchymal stromal cells dictates their immune or proinflammatory effects in kidney transplantation,” American Journal of Transplantation, vol. 12, no. 9, pp. 2373–2383, 2012. View at Publisher · View at Google Scholar · View at Scopus
  43. W. Ge, J. Jiang, J. Arp, W. Liu, B. Garcia, and H. Wang, “Regulatory T-cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression,” Transplantation, vol. 90, no. 12, pp. 1312–1320, 2010. View at Publisher · View at Google Scholar · View at Scopus
  44. M. E. J. Reinders, W. E. Fibbe, and T. J. Rabelink, “Multipotent mesenchymal stromal cell therapy in renal disease and kidney transplantation,” Nephrology Dialysis Transplantation, vol. 25, no. 1, pp. 17–24, 2010. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Zacharek, J. Chen, X. Cui et al., “Angiopoietin1/Tie2 and VEGF/Flk1 induced by MSC treatment amplifies angiogenesis and vascular stabilization after stroke,” Journal of Cerebral Blood Flow and Metabolism, vol. 27, no. 10, pp. 1684–1691, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. V. Ninichuk, O. Gross, S. Segerer et al., “Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice,” Kidney International, vol. 70, no. 1, pp. 121–129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Franquesa, E. Herrero, J. Torras et al., “Mesenchymal stem cell therapy prevents interstitial fibrosis and tubular atrophy in a rat kidney allograft model,” Stem Cells and Development, vol. 21, no. 17, pp. 3125–3135, 2012. View at Publisher · View at Google Scholar · View at Scopus
  48. J. Seok, H. S. Warrenb, A. G. Cuenca et al., “Genomic responses in mouse models poorly mimic human inflammatory diseases,” Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 9, pp. 3507–3512, 2013. View at Publisher · View at Google Scholar · View at Scopus
  49. J. Tolar, K. le Blanc, A. Keating, and B. R. Blazar, “Concise review: hitting the right spot with mesenchymal stromal cells,” Stem Cells, vol. 28, no. 8, pp. 1446–1455, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. J. Dillmann, F. C. Popp, B. Fillenberg et al., “Treatment-emergent adverse events after infusion of adherent stem cells: the MiSOT-I score for solid organ transplantation,” Trials, vol. 13, article 211, 2012. View at Publisher · View at Google Scholar · View at Scopus
  51. H. M. Kauffman, W. S. Cherikh, M. A. McBride, Y. Cheng, and D. W. Hanto, “Post-transplant de novo malignancies in renal transplant recipients: the past and present,” Transplant International, vol. 19, no. 8, pp. 607–620, 2006. View at Publisher · View at Google Scholar · View at Scopus
  52. S. Euvrard, “Skin cancers after organ transplants,” Presse Medicale, vol. 37, no. 10, pp. 1475–1479, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. S. Euvrard, J. Kanitakis, and A. Claudy, “Skin cancers after organ transplantation,” The New England Journal of Medicine, vol. 348, no. 17, pp. 1681–1691, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. R. Ramasamy, E. W.-F. Lam, I. Soeiro, V. Tisato, D. Bonnet, and F. Dazzi, “Mesenchymal stem cells inhibit proliferation and apoptosis of tumor cells: impact on in vivo tumor growth,” Leukemia, vol. 21, no. 2, pp. 304–310, 2007. View at Publisher · View at Google Scholar · View at Scopus
  55. S.-C. Hung, W.-P. Deng, W. K. Yang et al., “Mesenchymal stem cell targeting of microscopic tumors and tumor stroma development monitored by noninvasive in vivo positron emission tomography imaging,” Clinical Cancer Research, vol. 11, no. 21, pp. 7749–7756, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. P. Secchiero, S. Zorzet, C. Tripodo et al., “Human bone marrow mesenchymal stem cells display anti-cancer activity in SCID mice bearing disseminated non-Hodgkin's lymphoma xenografts,” PLoS ONE, vol. 5, no. 6, Article ID e11140, 2010. View at Publisher · View at Google Scholar · View at Scopus
  57. V. R. Dasari, K. Kaur, K. K. Velpula et al., “Up regulation of PTEN in glioma cells by cord blood mesenchymal stem cells inhibits migration via downregulation of the PI3K/Akt pathway,” PLoS ONE, vol. 5, no. 4, Article ID e10350, 2010. View at Publisher · View at Google Scholar · View at Scopus
  58. A. Y. Khakoo, S. Pati, S. A. Anderson et al., “Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcoma,” Journal of Experimental Medicine, vol. 203, no. 5, pp. 1235–1247, 2006. View at Publisher · View at Google Scholar · View at Scopus
  59. F. Casiraghi, G. Remuzzi, M. Abbate, and N. Perico, “Multipotent mesenchymal stromal cell therapy and risk of malignancies,” Stem Cell Reviews and Reports, vol. 9, no. 1, pp. 65–79, 2013. View at Publisher · View at Google Scholar · View at Scopus
  60. L. von Bahr, B. Sundberg, L. Lönnies et al., “Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy,” Biology of Blood and Marrow Transplantation, vol. 18, no. 4, pp. 557–564, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. C. Moermans, C. Lechanteur, E. Baudoux et al., “Impact of cotransplantation of mesenchymal stem cells on lung function after unrelated allogeneic hematopoietic stem cell transplantation following non-myeloablative conditioning,” Transplantation, vol. 98, pp. 348–353, 2014. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Franquesa, M. J. Hoogduijn, M. E. Reinders et al., “Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) Fourth Meeting: lessons learned from first clinical trials,” Transplantation, vol. 96, pp. 234–238, 2013. View at Google Scholar
  63. M. D. Griffin, A. E. Ryan, S. Alagesan, P. Lohan, O. Treacy, and T. Ritter, “Anti-donor immune responses elicited by allogeneic mesenchymal stem cells: what have we learned so far?” Immunology and Cell Biology, vol. 91, no. 1, pp. 40–51, 2013. View at Publisher · View at Google Scholar · View at Scopus
  64. L. C. Paul, “Chronic allograft nephropathy: an update,” Kidney International, vol. 56, no. 3, pp. 783–793, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. M. Pascual, T. Theruvath, T. Kawai, N. Tolkoff-Rubin, and A. Benedict Cosimi, “Strategies to improve long-term outcomes after renal transplantation,” The New England Journal of Medicine, vol. 346, no. 8, pp. 580–590, 2002. View at Publisher · View at Google Scholar · View at Scopus
  66. D. Serón and F. Moreso, “Protocol biopsies in renal transplantation: prognostic value of structural monitoring,” Kidney International, vol. 72, no. 6, pp. 690–697, 2007. View at Publisher · View at Google Scholar · View at Scopus
  67. K. Solez and L. C. Racusen, “The Banff classification revisited,” Kidney International, vol. 83, no. 2, pp. 201–206, 2013. View at Publisher · View at Google Scholar · View at Scopus
  68. K. Solez, R. B. Colvin, L. C. Racusen et al., “Banff 07 classification of renal allograft pathology: updates and future directions,” American Journal of Transplantation, vol. 8, no. 4, pp. 753–760, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. P. N. Furness and N. Taub, “International variation in the interpretation of renal transplant biopsies: report of the CERTPAP project,” Kidney International, vol. 60, no. 5, pp. 1998–2012, 2001. View at Publisher · View at Google Scholar · View at Scopus
  70. P. C. Grimm, P. Nickerson, J. Gough et al., “Computerized image analysis of Sirius Red-stained renal allograft biopsies as a surrogate marker to predict long-term allograft function,” Journal of the American Society of Nephrology, vol. 14, no. 6, pp. 1662–1668, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. M. M. D. Encarnacion, M. D. Griffin, J. M. Slezak et al., “Correlation of quantitative digital image analysis with the glomerular filtration rate in chronic allograft nephropathy,” American Journal of Transplantation, vol. 4, no. 2, pp. 248–256, 2004. View at Publisher · View at Google Scholar · View at Scopus
  72. E. M. Scholten, A. T. Rowshani, S. Cremers et al., “Untreated rejection in 6-month protocol biopsies is not associated with fibrosis in serial biopsies or with loss of graft function,” Journal of the American Society of Nephrology, vol. 17, no. 9, pp. 2622–2632, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. M. C. R.-V. Groningen, E. M. Scholten, P. M. Lelieveld et al., “Molecular comparison of calcineurin inhibitor-induced fibrogenic responses in protocol renal transplant biopsies,” Journal of the American Society of Nephrology, vol. 17, no. 3, pp. 881–888, 2006. View at Publisher · View at Google Scholar · View at Scopus
  74. A. T. Rowshani, E. M. Scholten, F. Bemelman et al., “No difference in degree of interstitial Sirius red-stained area in serial biopsies from area under concentration-over-time curves-guided cyclosporine versus tacrolimus-treated renal transplant recipients at one year,” Journal of the American Society of Nephrology, vol. 17, no. 1, pp. 305–312, 2006. View at Google Scholar
  75. S. Hariharan, M. A. McBride, W. S. Cherikh, C. B. Tolleris, B. A. Bresnahan, and C. P. Johnson, “Post-transplant renal function in the first year predicts long-term kidney transplant survival,” Kidney International, vol. 62, no. 1, pp. 311–318, 2002. View at Publisher · View at Google Scholar · View at Scopus
  76. K. Shaffi, K. Uhlig, R. D. Perrone et al., “Performance of creatinine-based GFR estimating equations in solid-organ transplant recipients,” American Journal of Kidney Diseases, vol. 63, no. 6, pp. 1007–1018, 2014. View at Publisher · View at Google Scholar · View at Scopus
  77. G. Filler, A. Yasin, and M. Medeiros, “Methods of assessing renal function,” Pediatric Nephrology, vol. 29, no. 2, pp. 183–192, 2014. View at Publisher · View at Google Scholar · View at Scopus
  78. M. G. De Alencastro, F. V. Veronese, A. R. Vicari, L. F. Gonçalves, and R. C. Manfro, “Evaluation of equations that estimate glomerular filtration rate in renal transplant recipients,” Minerva Urologica e Nefrologica, vol. 66, no. 1, pp. 87–95, 2014. View at Google Scholar · View at Scopus
  79. V. Lezaic, D. Mirkovic, S. Ristic et al., “Potential influence of tubular dysfunction on the difference between estimated and measured glomerular filtration rate after kidney transplantation,” Transplantation Proceedings, vol. 45, no. 4, pp. 1651–1654, 2013. View at Publisher · View at Google Scholar · View at Scopus
  80. J. V. Bonventre and L. Yang, “Kidney injury molecule-1,” Current Opinion in Critical Care, vol. 16, no. 6, pp. 556–561, 2010. View at Publisher · View at Google Scholar · View at Scopus
  81. S. G. Coca, R. Yalavarthy, J. Concato, and C. R. Parikh, “Biomarkers for the diagnosis and risk stratification of acute kidney injury: a systematic review,” Kidney International, vol. 73, no. 9, pp. 1008–1016, 2008. View at Publisher · View at Google Scholar · View at Scopus
  82. T. Ichimura, E. J. P. V. Asseldonk, B. D. Humphreys, L. Gunaratnam, J. S. Duffield, and J. V. Bonventre, “Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells,” Journal of Clinical Investigation, vol. 118, no. 5, pp. 1657–1668, 2008. View at Publisher · View at Google Scholar · View at Scopus
  83. C. R. Parikh, H. Thiessen-Philbrook, A. X. Garg et al., “Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of aki after cardiac surgery,” Clinical Journal of the American Society of Nephrology, vol. 8, no. 7, pp. 1079–1088, 2013. View at Publisher · View at Google Scholar · View at Scopus
  84. T. Ichimura, C. C. Hung, S. A. Yang, J. L. Stevens, and J. V. Bonventre, “Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury,” The American Journal of Physiology—Renal Physiology, vol. 286, no. 3, pp. F552–F563, 2004. View at Publisher · View at Google Scholar · View at Scopus
  85. J. L. Alge and J. M. Arthur, “Biomarkers of AKI: a review of mechanistic relevance and potential therapeutic implications,” Clinical Journal of the American Society of Nephrology, vol. 10, no. 1, pp. 147–155, 2015. View at Publisher · View at Google Scholar
  86. M. Streitz, T. Miloud, M. Kapinsky et al., “Standardization of whole blood immune phenotype monitoring for clinical trials: panels and methods from the ONE study,” Transplantation Research, vol. 2, article 17, 2013. View at Publisher · View at Google Scholar
  87. R. T. Gansevoort, R. Correa-Rotter, B. R. Hemmelgarn et al., “Chronic kidney disease and cardiovascular risk: epidemiology, mechanisms, and prevention,” The Lancet, vol. 382, no. 9889, pp. 339–352, 2013. View at Publisher · View at Google Scholar
  88. A. S. Go, G. M. Chertow, D. Fan, C. E. McCulloch, and C.-Y. Hsu, “Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization,” The New England Journal of Medicine, vol. 351, no. 13, pp. 1296–1305, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. R. Pruthi, R. Steenkamp, and T. Feest, “UK Renal Registry 16th annual report: chapter 8 survival and cause of death of UK adult patients on renal replacement therapy in 2012: national and centre-specific analyses,” Nephron. Clinical Practice, vol. 125, no. 1–4, pp. 139–169, 2013. View at Publisher · View at Google Scholar
  90. A. J. Collins, R. N. Foley, B. Chavers et al., “US renal data system 2013 annual data report,” American Journal of Kidney Diseases, vol. 63, no. 1, supplement, p. A7, 2014. View at Publisher · View at Google Scholar
  91. A. G. Jardine, “Assessing the relative risk of cardiovascular disease among renal transplant patients receiving tacrolimus or cyclosporine,” Transplant International, vol. 18, no. 4, pp. 379–384, 2005. View at Publisher · View at Google Scholar · View at Scopus
  92. M. Svensson, A. Jardine, B. Fellström, and H. Holdaas, “Prevention of cardiovascular disease after renal transplantation,” Current Opinion in Organ Transplantation, vol. 17, no. 4, pp. 393–400, 2012. View at Publisher · View at Google Scholar · View at Scopus
  93. M. A. Carpenter, M. R. Weir, D. B. Adey, A. A. House, A. G. Bostom, and J. W. Kusek, “Inadequacy of cardiovascular risk factor management in chronic kidney transplantation—evidence from the FAVORIT study,” Clinical Transplantation, vol. 26, no. 4, pp. E438–E446, 2012. View at Publisher · View at Google Scholar · View at Scopus
  94. A. K. Israni, J. J. Snyder, M. A. Skeans et al., “Predicting coronary heart disease after kidney transplantation: patient outcomes in renal transplantation (PORT) Study,” American Journal of Transplantation, vol. 10, no. 2, pp. 338–353, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. B. Fellström, A. G. Jardine, I. Soveri et al., “Renal dysfunction is a strong and independent risk factor for mortality and cardiovascular complications in renal transplantation,” American Journal of Transplantation, vol. 5, no. 8, pp. 1986–1991, 2005. View at Publisher · View at Google Scholar · View at Scopus
  96. H.-U. Meier-Kriesche, R. Baliga, and B. Kaplan, “Decreased renal function is a strong risk factor for cardiovascular death after renal transplantation,” Transplantation, vol. 75, no. 8, pp. 1291–1295, 2003. View at Publisher · View at Google Scholar · View at Scopus
  97. K. L. Lentine, D. C. Brennan, and M. A. Schnitzler, “Incidence and predictors of myocardial infarction after kidney transplantation,” Journal of the American Society of Nephrology, vol. 16, no. 2, pp. 496–506, 2005. View at Publisher · View at Google Scholar · View at Scopus
  98. D. E. Weiner, M. A. Carpenter, A. S. Levey et al., “Kidney function and risk of cardiovascular disease and mortality in kidney transplant recipients: the FAVORIT trial,” The American Journal of Transplantation, vol. 12, no. 9, pp. 2437–2445, 2012. View at Publisher · View at Google Scholar · View at Scopus
  99. D. Tousoulis, A. Briasoulis, C. Antoniades, E. Stefanadi, and C. Stefanadis, “Heart regeneration: what cells to use and how?” Current Opinion in Pharmacology, vol. 8, no. 2, pp. 211–218, 2008. View at Publisher · View at Google Scholar · View at Scopus
  100. M. E. Halkos, Z.-Q. Zhao, F. Kerendi et al., “Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction,” Basic Research in Cardiology, vol. 103, no. 6, pp. 525–536, 2008. View at Publisher · View at Google Scholar · View at Scopus
  101. L. C. Amado, A. P. Saliaris, K. H. Schuleri et al., “Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 32, pp. 11474–11479, 2005. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Amsalem, Y. Mardor, M. S. Feinberg et al., “Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium,” Circulation, vol. 116, no. 11, pp. I38–I45, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. J. Feygin, A. Mansoor, P. Eckman, C. Swingen, and J. Zhang, “Functional and bioenergetic modulations in the infarct border zone following autologous mesenchymal stem cell transplantation,” American Journal of Physiology: Heart and Circulatory Physiology, vol. 293, no. 3, pp. H1772–H1780, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. J. G. Shake, P. J. Gruber, W. A. Baumgartner et al., “Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects,” The Annals of Thoracic Surgery, vol. 73, no. 6, pp. 1919–1926, 2002. View at Publisher · View at Google Scholar · View at Scopus
  105. A. F. G. Godier-Furnémont, T. P. Martens, M. S. Koeckert et al., “Composite scaffold provides a cell delivery platform for cardiovascular repair,” Proceedings of the National Academy of Sciences of the United States of America, vol. 108, no. 19, pp. 7974–7979, 2011. View at Publisher · View at Google Scholar · View at Scopus
  106. W. Ge, J. Jiang, M. L. Baroja et al., “Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance,” American Journal of Transplantation, vol. 9, no. 8, pp. 1760–1772, 2009. View at Publisher · View at Google Scholar · View at Scopus
  107. F. C. Popp, E. Eggenhofer, P. Renner et al., “Mesenchymal stem cells can induce long-term acceptance of solid organ allografts in synergy with low-dose mycophenolate,” Transplant Immunology, vol. 20, no. 1-2, pp. 55–60, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. S.-L. Chen, W.-W. Fang, F. Ye et al., “Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction,” The American Journal of Cardiology, vol. 94, no. 1, pp. 92–95, 2004. View at Publisher · View at Google Scholar · View at Scopus
  109. J. Bartunek, A. Behfar, D. Dolatabadi et al., “Cardiopoietic stem cell therapy in heart failure: the C-CURE (Cardiopoietic stem Cell therapy in heart failURE) multicenter randomized trial with lineage-specified biologics,” Journal of the American College of Cardiology, vol. 61, no. 23, pp. 2329–2338, 2013. View at Publisher · View at Google Scholar
  110. V. Karantalis, D. L. Difede, G. Gerstenblith et al., “Autologous mesenchymal stem cells produce concordant improvements in regional function, tissue perfusion, and fibrotic burden when administered to patients undergoing coronary artery bypass grafting: the prospective randomized study of mesenchymal stem cell therapy in patients undergoing cardiac surgery (PROMETHEUS) trial,” Circulation Research, vol. 114, no. 8, pp. 1302–1310, 2014. View at Publisher · View at Google Scholar · View at Scopus
  111. M. R.-V. Rhijn, M. E. J. Reinders, A. De Klein et al., “Mesenchymal stem cells derived from adipose tissue are not affected by renal disease,” Kidney International, vol. 82, no. 7, pp. 748–758, 2012. View at Publisher · View at Google Scholar · View at Scopus
  112. M. E. J. Reinders, M. Roemeling-Van Rhijn, M. Khairoun et al., “Bone marrow-derived mesenchymal stromal cells from patients with end-stage renal disease are suitable for autologous therapy,” Cytotherapy, vol. 15, no. 6, pp. 663–672, 2013. View at Publisher · View at Google Scholar · View at Scopus
  113. M. Khairoun and S. S Korevaar, “Human Bone Marrow- and Adipose Tissue-derived Mesenchymal Stromal Cells are Immunosuppressive In vitro and in a Humanized Allograft Rejection Model,” Journal of Stem Cell Research & Therapy, supplement 6, Article ID 20780, 2013. View at Publisher · View at Google Scholar
  114. D. C. Brennan, C. Legendre, D. Patel et al., “Cytomegalovirus incidence between everolimus versus mycophenolate in de novo renal transplants: pooled analysis of three clinical trials,” The American Journal of Transplantation, vol. 11, no. 11, pp. 2453–2462, 2011. View at Publisher · View at Google Scholar · View at Scopus
  115. S. Euvrard, E. Morelon, L. Rostaing et al., “Sirolimus and secondary skin-cancer prevention in kidney transplantation,” The New England Journal of Medicine, vol. 367, no. 4, pp. 329–339, 2012. View at Publisher · View at Google Scholar · View at Scopus
  116. J. M. Hoogendijk-van Den Akker, P. N. Harden, A. J. Hoitsma et al., “Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus,” Journal of Clinical Oncology, vol. 31, no. 10, pp. 1317–1323, 2013. View at Publisher · View at Google Scholar · View at Scopus
  117. S. B. Campbell, R. Walker, S. S. Tai, Q. Jiang, and G. R. Russ, “Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer,” American Journal of Transplantation, vol. 12, no. 5, pp. 1146–1156, 2012. View at Publisher · View at Google Scholar · View at Scopus
  118. O. R. Colegio, A. Hanlon, E. B. Olasz, and J. A. Carucci, “Sirolimus reduces cutaneous squamous cell carcinomas in transplantation recipients,” Journal of Clinical Oncology, vol. 31, no. 26, pp. 3297–3298, 2013. View at Publisher · View at Google Scholar · View at Scopus
  119. J. W. de Fijter and J. N. Bouwes Bavinck, “Reply to O.R. Colegio et al,” Journal of Clinical Oncology, vol. 31, no. 26, p. 3298, 2013. View at Google Scholar