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Pediatric Nephrology
Erschienen in: Pediatric Nephrology 2/2018

23.02.2017 | Review

Cell therapeutic approaches to immunosuppression after clinical kidney transplantation

verfasst von: Christian Morath, Anita Schmitt, Florian Kälble, Martin Zeier, Michael Schmitt, Flavius Sandra-Petrescu, Gerhard Opelz, Peter Terness, Matthias Schaier, Christian Kleist

Erschienen in: Pediatric Nephrology | Ausgabe 2/2018

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Abstract

Refinement of immunosuppressive strategies has led to further improvement of kidney graft survival in recent years. Currently, the main limitations to long-term graft survival are life-threatening side effects of immunosuppression and chronic allograft injury, emphasizing the need for innovative immunosuppressive regimens that resolve this therapeutic dilemma. Several cell therapeutic approaches to immunosuppression and donor-specific unresponsiveness have been tested in early phase I and phase II clinical trials in kidney transplantation. The aim of this overview is to summarize current cell therapeutic approaches to immunosuppression in clinical kidney transplantation with a focus on myeloid suppressor cell therapy by mitomycin C-induced cells (MICs). MICs show great promise as a therapeutic agent to achieve the rapid and durable establishment of donor-unresponsiveness in living-donor kidney transplantation. Cell-based therapeutic approaches may eventually revolutionize immunosuppression in kidney transplantation in the near future.
Literatur
1.
Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK (1999) Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 341:1725–1730CrossRefPubMed
2.
Morath C, Schmitt A, Zeier M, Schmitt M, Sandra-Petrescu F, Opelz G, Terness P, Schaier M, Kleist C (2015) Cell therapy for immunosuppression after kidney transplantation. Langenbecks Arch Surg 400:541–550CrossRefPubMed
3.
Billingham RE, Brent L, Medawar PB (1953) Actively acquired tolerance of foreign cells. Nature 172:603–606CrossRefPubMed
4.
Pearl JP, Preston E, Kirk AD (2003) Tolerance: is it achievable in pediatric solid organ transplantation? Pediatr Clin N Am 50:1261–1281CrossRef
5.
Girlanda R, Kirk AD (2007) Frontiers in nephrology: immune tolerance to allografts in humans. J Am Soc Nephrol 18:2242–2251CrossRefPubMed
6.
Li L, Wozniak LJ, Rodder S, Heish S, Talisetti A, Wang Q, Esquivel C, Cox K, Chen R, McDiarmid SV, Sarwal MM (2012) A common peripheral blood gene set for diagnosis of operational tolerance in pediatric and adult liver transplantation. Am J Transplant 12:1218–1228CrossRefPubMed
7.
Kamran Hejazi Kenari S, Mirzakhani H, Saidi RF (2014) Pediatric transplantation and tolerance: past, present, and future. Pediatr Transplant 18:435–445CrossRefPubMed
8.
Talisetti A, Hurwitz M, Sarwal M, Berquist W, Castillo R, Bass D, Concepcion W, Esquivel CO, Cox K (2010) Analysis of clinical variables associated with tolerance in pediatric liver transplant recipients. Pediatr Transplant 14:976–979CrossRefPubMed
9.
Schmetterer KG, Neunkirchner A, Pickl WF (2012) Naturally occurring regulatory T cells: markers, mechanisms, and manipulation. FASEB J 26:2253–2276CrossRefPubMed
10.
Abbas AK, Benoist C, Bluestone JA, Campbell DJ, Ghosh S, Hori S, Jiang S, Kuchroo VK, Mathis D, Roncarolo MG, Rudensky A, Sakaguchi S, Shevach EM, Vignali DA, Ziegler SF (2013) Regulatory T cells: recommendations to simplify the nomenclature. Nat Immunol 14:307–308CrossRefPubMed
11.
Haribhai D, Williams JB, Jia S, Nickerson D, Schmitt EG, Edwards B, Ziegelbauer J, Yassai M, Li SH, Relland LM, Wise PM, Chen A, Zheng YQ, Simpson PM, Gorski J, Salzman NH, Hessner MJ, Chatila TA, Williams CB (2011) A requisite role for induced regulatory T cells in tolerance based on expanding antigen receptor diversity. Immunity 35:109–122CrossRefPubMedPubMedCentral
12.
Liu W, Putnam AL, Xu-Yu Z, Szot GL, Lee MR, Zhu S, Gottlieb PA, Kapranov P, Gingeras TR, Fazekas de St Groth B, Clayberger C, Soper DM, Ziegler SF (2006) CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203:1701–1711CrossRefPubMedPubMedCentral
13.
14.
15.
16.
17.
Shevach EM (2009) Mechanisms of foxp3+ T regulatory cell-mediated suppression. Immunity 30:636–645CrossRefPubMed
18.
Aluvihare VR, Kallikourdis M, Betz AG (2004) Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5:266–271CrossRefPubMed
19.
Aluvihare VR, Kallikourdis M, Betz AG (2005) Tolerance, suppression and the fetal allograft. J Mol Med (Berl) 83:88–96CrossRef
20.
Aluvihare VR, Betz AG (2006) The role of regulatory T cells in alloantigen tolerance. Immunol Rev 212:330–343CrossRefPubMed
21.
Steinborn A, Haensch GM, Mahnke K, Schmitt E, Toermer A, Meuer S, Sohn C (2008) Distinct subsets of regulatory T cells during pregnancy: is the imbalance of these subsets involved in the pathogenesis of preeclampsia? Clin Immunol 129:401–412CrossRefPubMed
22.
Kisielewicz A, Schaier M, Schmitt E, Hug F, Haensch GM, Meuer S, Zeier M, Sohn C, Steinborn A (2010) A distinct subset of HLA-DR+-regulatory T cells is involved in the induction of preterm labor during pregnancy and in the induction of organ rejection after transplantation. Clin Immunol 137:209–220CrossRefPubMed
23.
Schober L, Radnai D, Schmitt E, Mahnke K, Sohn C, Steinborn A (2012) Term and preterm labor: decreased suppressive activity and changes in composition of the regulatory T-cell pool. Immunol Cell Biol 90:935–944CrossRefPubMed
24.
Steinborn A, Schmitt E, Kisielewicz A, Rechenberg S, Seissler N, Mahnke K, Schaier M, Zeier M, Sohn C (2012) Pregnancy-associated diseases are characterized by the composition of the systemic regulatory T cell (Treg) pool with distinct subsets of Tregs. Clin Exp Immunol 167:84–98CrossRefPubMedPubMedCentral
25.
Wagner MI, Mai C, Schmitt E, Mahnke K, Meuer S, Eckstein V, Ho AD, Schaier M, Zeier M, Spratte J, Fluhr H, Steinborn A (2015) The role of recent thymic emigrant-regulatory T-cell (RTE-Treg) differentiation during pregnancy. Immunol Cell Biol 93:858–867CrossRefPubMed
26.
Wagner MI, Jost M, Spratte J, Schaier M, Mahnke K, Meuer S, Zeier M, Steinborn A (2016) Differentiation of ICOS(+) and ICOS(−) recent thymic emigrant regulatory T cells (RTE Tregs) during normal pregnancy, pre-eclampsia and HELLP syndrome. Clin Exp Immunol 183:129–142CrossRefPubMed
27.
Schaier M, Seissler N, Schmitt E, Meuer S, Hug F, Zeier M, Steinborn A (2012) DR(high+)CD45RA(−)-Tregs potentially affect the suppressive activity of the total Treg pool in renal transplant patients. PLoS One 7:e34208CrossRefPubMedPubMedCentral
28.
Schaier M, Seissler N, Becker LE, Schaefer SM, Schmitt E, Meuer S, Hug F, Sommerer C, Waldherr R, Zeier M, Steinborn A (2013) The extent of HLA-DR expression on HLA-DR(+) Tregs allows the identification of patients with clinically relevant borderline rejection. Transpl Int 26:290–299CrossRefPubMed
29.
30.
Mahnke K, Bedke T, Enk AH (2007) Regulatory conversation between antigen presenting cells and regulatory T cells enhance immune suppression. Cell Immunol 250:1–13CrossRefPubMed
31.
Hutchinson JA, Geissler EK (2015) Now or never? The case for cell-based immunosuppression in kidney transplantation. Kidney Int 87:1116–1124CrossRefPubMed
32.
Steinman RM (2012) Decisions about dendritic cells: past, present, and future. Annu Rev Immunol 30:1–22CrossRefPubMed
33.
Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH (2008) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 358:353–361CrossRefPubMedPubMedCentral
34.
Kawai T, Sachs DH, Sprangers B, Spitzer TR, Saidman SL, Zorn E, Tolkoff-Rubin N, Preffer F, Crisalli K, Gao B, Wong W, Morris H, LoCascio SA, Sayre P, Shonts B, Williams WW Jr, Smith RN, Colvin RB, Sykes M, Cosimi AB (2014) Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am J Transplant 14:1599–1611CrossRefPubMedPubMedCentral
35.
Andre S, Tough DF, Lacroix-Desmazes S, Kaveri SV, Bayry J (2009) Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity: immunopathogenesis and therapeutic implications. Am J Pathol 174:1575–1587CrossRefPubMedPubMedCentral
36.
37.
Wood KJ, Bushell A, Hester J (2012) Regulatory immune cells in transplantation. Nat Rev Immunol 12:417–430CrossRefPubMed
38.
Gallon L, Traitanon O, Yu Y, Shi B, Leventhal JR, Miller J, Mas V, Xu L, Mathew JM (2015) Differential effects of calcineurin and mammalian target of rapamycin inhibitors on alloreactive Th1, Th17, and regulatory T cells. Transplantation 99:1774–1784CrossRefPubMed
39.
Kleist C, Sandra-Petrescu F, Jiga L, Dittmar L, Mohr E, Greil J, Mier W, Becker LE, Lang P, Opelz G, Terness P (2015) Generation of suppressive blood cells for control of allograft rejection. Clin Sci (Lond) 128:593–607CrossRef
40.
Terness P, Oelert T, Ehser S, Chuang JJ, Lahdou I, Kleist C, Velten F, Hämmerling GJ, Arnold B, Opelz G (2008) Mitomycin C-treated dendritic cells inactivate autoreactive T cells: toward the development of a tolerogenic vaccine in autoimmune diseases. Proc Natl Acad Sci USA 105:18442–18447CrossRefPubMedPubMedCentral
41.
Dittmar L, Mohr E, Kleist C, Ehser S, Demirdizen H, Sandra-Petrescu F, Hundemer M, Opelz G, Terness P (2015) Immunosuppressive properties of mitomycin C-incubated human myeloid blood cells (MIC) in vitro. Hum Immunol 76:480–487
42.
Peng Y, Ke M, Xu L, Liu L, Chen X, Xia W, Li X, Chen Z, Ma J, Liao D, Li G, Fang J, Pan G, Xiang AP (2013) Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study. Transplantation 95:161–168CrossRefPubMed
43.
Perico N, Casiraghi F, Gotti E, Introna M, Todeschini M, Cavinato RA, Capelli C, Rambaldi A, Cassis P, Rizzo P, Cortinovis M, Noris M, Remuzzi G (2013) Mesenchymal stromal cells and kidney transplantation: pretransplant infusion protects from graft dysfunction while fostering immunoregulation. Transpl Int 26:867–878CrossRefPubMed
44.
Perico N, Casiraghi F, Introna M, Gotti E, Todeschini M, Cavinato RA, Capelli C, Rambaldi A, Cassis P, Rizzo P, Cortinovis M, Marasà M, Golay J, Noris M, Remuzzi G (2011) Autologous mesenchymal stromal cells and kidney transplantation: a pilot study of safety and clinical feasibility. Clin J Am Soc Nephrol 6:412–422CrossRefPubMedPubMedCentral
45.
Reinders ME, Dreyer GJ, Bank JR, Roelofs H, Heidt S, Roelen DL, Zandvliet ML, Huurman VA, Fibbe WE, van Kooten C, Claas FH, Rabelink TJ, de Fijter JW (2015) Safety of allogeneic bone marrow derived mesenchymal stromal cell therapy in renal transplant recipients: the neptune study. J Transl Med 13:344CrossRefPubMedPubMedCentral
46.
Reinders ME, de Fijter JW, Roelofs H, Bajema IM, de Vries DK, Schaapherder AF, Claas FH, van Miert PP, Roelen DL, van Kooten C, Fibbe WE, Rabelink TJ (2013) Autologous bone marrow-derived mesenchymal stromal cells for the treatment of allograft rejection after renal transplantation: results of a phase I study. Stem Cells Transl Med 2:107–111CrossRefPubMedPubMedCentral
47.
Tan J, Wu W, Xu X, Liao L, Zheng F, Messinger S, Sun X, Chen J, Yang S, Cai J, Gao X, Pileggi A, Ricordi C (2012) Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 307:1169–1177CrossRefPubMed
48.
Mudrabettu C, Kumar V, Rakha A, Yadav AK, Ramachandran R, Kanwar DB, Nada R, Minz M, Sakhuja V, Marwaha N, Jha V (2015) Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: a pilot study. Nephrology (Carlton) 20:25–33CrossRef
49.
Rakha A, Todeschini M, Casiraghi F (2014) Assessment of anti-donor T cell proliferation and cytotoxic T lymphocyte-mediated lympholysis in living donor kidney transplant patients. Methods Mol Biol 1213:355–364CrossRefPubMed
50.
Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S (2011) Induced immune tolerance for kidney transplantation. N Engl J Med 365:1359–1360CrossRefPubMedPubMedCentral
51.
Kawai T, Cosimi AB, Sachs DH (2011) Preclinical and clinical studies on the induction of renal allograft tolerance through transient mixed chimerism. Curr Opin Organ Transplant 16:366–371CrossRefPubMedPubMedCentral
52.
Sachs DH, Sykes M, Kawai T, Cosimi AB (2011) Immuno-intervention for the induction of transplantation tolerance through mixed chimerism. Semin Immunol 23:165–173CrossRefPubMedPubMedCentral
53.
Kawai T, Sachs DH, Sykes M, Cosimi AB, Immune Tolerance Network (2013) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 368:1850–1852CrossRefPubMedPubMedCentral
54.
Leventhal JR, Mathew JM, Salomon DR, Kurian SM, Friedewald JJ, Gallon L, Konieczna I, Tambur AR, Charette J, Levitsky J, Jie C, Kanwar YS, Abecassis MM, Miller J (2016) Nonchimeric HLA-identical renal transplant tolerance: regulatory immunophenotypic/genomic biomarkers. Am J Transplant 16:221–234CrossRefPubMed
55.
Ciancio G, Sageshima J, Akpinar E, Gaynor JJ, Chen L, Zarak A, Hanson L, Tueros L, Guerra G, Mattiazzi A, Kupin W, Roth D, Ricordi C, Burke GW 3rd (2013) A randomized pilot study of donor stem cell infusion in living-related kidney transplant recipients receiving alemtuzumab. Transplantation 96:800–806CrossRefPubMed
56.
Scandling JD, Busque S, Shizuru JA, Lowsky R, Hoppe R, Dejbakhsh-Jones S, Jensen K, Shori A, Strober JA, Lavori P, Turnbull BB, Engleman EG, Strober S (2015) Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant 15:695–704CrossRefPubMed
57.
Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, Hoppe RT, Lowsky R, Engleman EG, Strober S (2008) Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med 358:362–368CrossRefPubMed
58.
Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S (2012) Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant 12:1133–1145CrossRefPubMedPubMedCentral
59.
Strober S, Benike C, Krishnaswamy S, Engleman EG, Grumet FC (2000) Clinical transplantation tolerance twelve years after prospective withdrawal of immunosuppressive drugs: studies of chimerism and anti-donor reactivity. Transplantation 69:1549–1554CrossRefPubMed
60.
Millan MT, Shizuru JA, Hoffmann P, Dejbakhsh-Jones S, Scandling JD, Grumet FC, Tan JC, Salvatierra O, Hoppe RT, Strober S (2002) Mixed chimerism and immunosuppressive drug withdrawal after HLA-mismatched kidney and hematopoietic progenitor transplantation. Transplantation 73:1386–1391CrossRefPubMed
61.
Geissler EK (2012) The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant Res 1:11CrossRefPubMedPubMedCentral
62.
Hutchinson JA, Riquelme P, Sawitzki B, Tomiuk S, Miqueu P, Zuhayra M, Oberg HH, Pascher A, Lützen U, Janssen U, Broichhausen C, Renders L, Thaiss F, Scheuermann E, Henze E, Volk HD, Chatenoud L, Lechler RI, Wood KJ, Kabelitz D, Schlitt HJ, Geissler EK, Fändrich F (2011) Cutting edge: immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients. J Immunol 187:2072–2078CrossRefPubMed
63.
Hutchinson JA, Brem-Exner BG, Riquelme P, Roelen D, Schulze M, Ivens K, Grabensee B, Witzke O, Philipp T, Renders L, Humpe A, Sotnikova A, Matthäi M, Heumann A, Gövert F, Schulte T, Kabelitz D, Claas FH, Geissler EK, Kunzendorf U, Fändrich F (2008) A cell-based approach to the minimization of immunosuppression in renal transplantation. Transpl Int 21:742–754CrossRefPubMed
64.
Leventhal J, Miller J, Abecassis M, Tollerud DJ, Ildstad ST (2013) Evolving approaches of hematopoietic stem cell-based therapies to induce tolerance to organ transplants: the long road to tolerance. Clin Pharmacol Ther 93:36–45CrossRefPubMed
65.
Spitzer TR, Sykes M, Tolkoff-Rubin N, Kawai T, McAfee SL, Dey BR, Ballen K, Delmonico F, Saidman S, Sachs DH, Cosimi AB (2011) Long-term follow-up of recipients of combined human leukocyte antigen-matched bone marrow and kidney transplantation for multiple myeloma with end-stage renal disease. Transplantation 91:672–676CrossRefPubMedPubMedCentral
66.
Leventhal JR, Elliott MJ, Yolcu ES, Bozulic LD, Tollerud DJ, Mathew JM, Konieczna I, Ison MG, Galvin J, Mehta J, Badder MD, Abecassis MM, Miller J, Gallon L, Ildstad ST (2015) Immune reconstitution/immunocompetence in recipients of kidney plus hematopoietic stem/facilitating cell transplants. Transplantation 99:288–298CrossRefPubMed
67.
Engela AU, Baan CC, Dor FJ, Weimar W, Hoogduijn MJ (2012) On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation. Front Immunol 3:126CrossRefPubMedPubMedCentral
68.
Qi H, Chen G, Huang Y, Si Z, Li J (2015) Foxp3-modified bone marrow mesenchymal stem cells promotes liver allograft tolerance through the generation of regulatory T cells in rats. J Transl Med 13:274CrossRefPubMedPubMedCentral
69.
van der Net JB, Bushell A, Wood KJ, Harden PN (2016) Regulatory T cells: first steps of clinical application in solid organ transplantation. Transpl Int 29:3–11PubMed
70.
Golovina TN, Mikheeva T, Suhoski MM, Aqui NA, Tai VC, Shan X, Liu R, Balcarcel RR, Fisher N, Levine BL, Carroll RG, Warner N, Blazar BR, June CH, Riley JL (2008) CD28 costimulation is essential for human T regulatory expansion and function. J Immunol 181:2855–2868CrossRefPubMedPubMedCentral
71.
Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE (2011) Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood 117:1061–1070CrossRefPubMedPubMedCentral
72.
Di Ianni M, Falzetti F, Carotti A, Terenzi A, Castellino F, Bonifacio E, Del Papa B, Zei T, Ostini RI, Cecchini D, Aloisi T, Perruccio K, Ruggeri L, Balucani C, Pierini A, Sportoletti P, Aristei C, Falini B, Reisner Y, Velardi A, Aversa F, Martelli MF (2011) Tregs prevent GVHD and promote immune reconstitution in HLA-haploidentical transplantation. Blood 117:3921–3928CrossRefPubMed
73.
Edozie FC, Nova-Lamperti EA, Povoleri GA, Scotta C, John S, Lombardi G, Afzali B (2014) Regulatory T-cell therapy in the induction of transplant tolerance: the issue of subpopulations. Transplantation 98:370–379CrossRefPubMed
74.
75.
Hutchinson JA, Riquelme P, Geissler EK, Fandrich F (2011) Human regulatory macrophages. Methods Mol Biol 677:181–192CrossRefPubMed
76.
Hutchinson JA, Riquelme P, Brem-Exner BG, Schulze M, Matthäi M, Renders L, Kunzendorf U, Geissler EK, Fändrich F (2008) Transplant acceptance-inducing cells as an immune-conditioning therapy in renal transplantation. Transpl Int 21:728–741CrossRefPubMed
77.
Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M (2011) Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care 34:2026–2032CrossRefPubMedPubMedCentral
78.
79.
Dilek N, Poirier N, Usal C, Martinet B, Blancho G, Vanhove B (2012) Control of transplant tolerance and intragraft regulatory T cell localization by myeloid-derived suppressor cells and CCL5. J Immunol 188:4209–4216CrossRefPubMed
80.
Dugast AS, Haudebourg T, Coulon F, Heslan M, Haspot F, Poirier N, Vuillefroy de Silly R, Usal C, Smit H, Martinet B, Thebault P, Renaudin K, Vanhove B (2008) Myeloid-derived suppressor cells accumulate in kidney allograft tolerance and specifically suppress effector T cell expansion. J Immunol 180:7898–7906CrossRefPubMed
81.
Dilek N, Vuillefroy de Silly R, Blancho G, Vanhove B (2012) Myeloid-derived suppressor cells: mechanisms of action and recent advances in their role in transplant tolerance. Front Immunol 3:208CrossRefPubMedPubMedCentral
82.
Ehser S, Chuang JJ, Kleist C, Sandra-Petrescu F, Iancu M, Wang D, Opelz G, Terness P (2008) Suppressive dendritic cells as a tool for controlling allograft rejection in organ transplantation: promises and difficulties. Hum Immunol 69:165–173CrossRefPubMed
83.
Thomson AW, Zahorchak AF, Ezzelarab MB, Butterfield LH, Lakkis FG, Metes DM (2016) Prospective clinical testing of regulatory dendritic cells in organ transplantation. Front Immunol 7:15CrossRefPubMedPubMedCentral
84.
Verweij J, Pinedo HM (1990) Mitomycin C: mechanism of action, usefulness and limitations. Anticancer Drugs 1:5–13CrossRefPubMed
85.
86.
Wang D, Kleist C, Ehser S, Opelz G, Terness P (2006) Ex vivo perfusion with mitomycin C containing solution prolongs heart graft survival in rats. Transplantation 82:1537–1540CrossRefPubMed
87.
Jiga LP, Bauer TM, Chuang JJ, Opelz G, Terness P (2004) Generation of tolerogenic dendritic cells by treatment with mitomycin C: inhibition of allogeneic T-cell response is mediated by downregulation of ICAM-1, CD80, and CD86. Transplantation 77:1761–1764CrossRefPubMed
88.
Jiga LP, Ehser S, Kleist C, Opelz G, Terness P (2007) Inhibition of heart allograft rejection with mitomycin C-treated donor dendritic cells. Transplantation 83:347–350CrossRefPubMed
89.
Tanigawa T, Gotoh M, Nagano H, Ota H, Fukuzaki T, Sakon M, Monden M (1999) Injection of mitomycin-C-treated spleen cells induces donor-specific unresponsiveness to cardiac allografts in rats. Transplantation 67:653–658CrossRefPubMed
90.
Radu CA, Kiefer J, Gebhard MM, Bigdeli AK, Schmidt VJ, Germann G, Lehnhardt M, Terness P, Kneser U, Kremer T (2015) Local administration of Mitomycin-C-Treated peripheral blood mononuclear cells (PBMCs) prolongs allograft survival in vascularized composite allotransplantation. Microsurgery. doi:10.​1002/​micr.​30003 PubMed
91.
Yamaguchi Y, Harland R, Wyble C, Mori K, Bollinger RR (1989) Variable allograft responses to pretreatment with donor splenocytes treated with mitomycin C in the rat. Transplantation 47:360–363CrossRefPubMed
92.
Kleist C, Mohr E, Gaikwad S, Dittmar L, Kuerten S, Platten M, Mier W, Schmitt M, Opelz G, Terness P (2016) Autoantigen-specific immunosuppression with tolerogenic peripheral blood cells prevents relapses in a mouse model of relapsing-remitting multiple sclerosis. J Transl Med 14:99CrossRefPubMedPubMedCentral
93.
Liu L, Wang F, Zheng Y, Yuan X, Wang D, Zeng W, He X, Wang C, Deng S (2014) Pretreatment of transfused donor splenocytes and allografts with mitomycin C attenuates acute rejection in heart transplantation in mice. Transplant Proc 46:1169–1174CrossRefPubMed
94.
Matsuyama S, Gunji T, Ise K, Sato Y, Saito T, Gotoh M (2003) Permanent acceptance of mitomycin C-treated islet allograft. Transplantation 76:65–71CrossRefPubMed
95.
Grochowiecki T, Gotoh M, Dono K, Takeda Y, Nishihara M, Ohta Y, Kimura F, Ohzato H, Umeshita K, Sakon M, Monden M (1998) Pretreatment of crude pancreatic islets with mitomycin C (MMC) prolongs islet graft survival in a xenogeneic rat-to-mouse model. Cell Transplant 7:411–412CrossRefPubMed
96.
Ilic N, Savic S, Siegel E, Atkinson K, Tasic L (2012) Examination of the regulatory frameworks applicable to biologic drugs (including stem cells and their progeny) in Europe, the U.S., and Australia: part II—a method of software documentary analysis. Stem Cells Transl Med 1:909–920CrossRefPubMedPubMedCentral
Metadaten
Titel
Cell therapeutic approaches to immunosuppression after clinical kidney transplantation
verfasst von
Christian Morath
Anita Schmitt
Florian Kälble
Martin Zeier
Michael Schmitt
Flavius Sandra-Petrescu
Gerhard Opelz
Peter Terness
Matthias Schaier
Christian Kleist
Publikationsdatum
23.02.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 2/2018
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-017-3599-2

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Augentropfen mit niedrig dosiertem Atropin können helfen, das Fortschreiten einer Kurzsichtigkeit bei Kindern zumindest zu verlangsamen, wie die Ergebnisse einer aktuellen Studie mit verschiedenen Dosierungen zeigen.

Spinale Muskelatrophie: Neugeborenen-Screening lohnt sich

18.04.2024 Spinale Muskelatrophien Nachrichten

Seit 2021 ist die Untersuchung auf spinale Muskelatrophie Teil des Neugeborenen-Screenings in Deutschland. Eine Studie liefert weitere Evidenz für den Nutzen der Maßnahme.

Fünf Dinge, die im Kindernotfall besser zu unterlassen sind

18.04.2024 Pädiatrische Notfallmedizin Nachrichten

Im Choosing-Wisely-Programm, das für die deutsche Initiative „Klug entscheiden“ Pate gestanden hat, sind erstmals Empfehlungen zum Umgang mit Notfällen von Kindern erschienen. Fünf Dinge gilt es demnach zu vermeiden.

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