BACKGROUND: Endothelial cells (ECs) embedded within 3-dimensional matrices (MEEC) control lumenal inflammation and intimal hyperplasia when placed in the vascular adventitia. Matrix embedding alters endothelial immunogenicity in vitro. T-helper (Th) cell-driven host immunity is an impediment of allogeneic grafts. We aimed to identify if modulation of Th balance would affect immune compatibility and endothelial regulation of vascular repair in vivo. METHODS: Pigs (n = 4/group) underwent carotid artery balloon injury and were left untreated (Group 1) or received perivascular porcine MEEC implants (Group 2), 12 days of cyclosporine A (CsA; Group 3), or MEEC and CsA (Group 4). Host immune reactivity was analyzed after 28 and 90 days. RESULTS: MEEC treatment induced formation of EC-specific immunoglobulin (Ig) G(1) antibodies (41 +/- 6 mean fluorescence intensity [MFI]) and differentiation of host splenocytes into Th2, but not Th1, cytokine-producing cells (interleukin [IL]-4, 242 +/- 102; IL-10, 273 +/- 114 number of spots). Concomitant CsA therapy reduced IgG(1) antibody frequency (25 +/- 2 MFI; p < 0.02) and Th2-cytokine producing splenocytes upon MEEC treatment (IL-4, 157 +/- 19; IL-10, 124 +/- 26 number of spots; p < 0.05). MEECs inhibited luminal occlusion 28 and 90 days after balloon injury (12 +/- 7%) vs untreated controls (68 +/- 14%; p < 0.001) but to a lesser extent with concomitant CsA treatment (34 +/- 13%; p < 0.02 vs Group 2). CONCLUSIONS: MEECs do not induce a significant Th1-driven immune response but do enhance differentiation of splenocytes into cells producing Th2 cytokine. Reduction in this Th2 response reduces the vasoregulatory effects of allogeneic ECs after injury.
BACKGROUND: Endothelial cells (ECs) embedded within 3-dimensional matrices (MEEC) control lumenal inflammation and intimal hyperplasia when placed in the vascular adventitia. Matrix embedding alters endothelial immunogenicity in vitro. T-helper (Th) cell-driven host immunity is an impediment of allogeneic grafts. We aimed to identify if modulation of Th balance would affect immune compatibility and endothelial regulation of vascular repair in vivo. METHODS:Pigs (n = 4/group) underwent carotid artery balloon injury and were left untreated (Group 1) or received perivascular porcine MEEC implants (Group 2), 12 days of cyclosporine A (CsA; Group 3), or MEEC and CsA (Group 4). Host immune reactivity was analyzed after 28 and 90 days. RESULTS:MEEC treatment induced formation of EC-specific immunoglobulin (Ig) G(1) antibodies (41 +/- 6 mean fluorescence intensity [MFI]) and differentiation of host splenocytes into Th2, but not Th1, cytokine-producing cells (interleukin [IL]-4, 242 +/- 102; IL-10, 273 +/- 114 number of spots). Concomitant CsA therapy reduced IgG(1) antibody frequency (25 +/- 2 MFI; p < 0.02) and Th2-cytokine producing splenocytes upon MEEC treatment (IL-4, 157 +/- 19; IL-10, 124 +/- 26 number of spots; p < 0.05). MEECs inhibited luminal occlusion 28 and 90 days after balloon injury (12 +/- 7%) vs untreated controls (68 +/- 14%; p < 0.001) but to a lesser extent with concomitant CsA treatment (34 +/- 13%; p < 0.02 vs Group 2). CONCLUSIONS: MEECs do not induce a significant Th1-driven immune response but do enhance differentiation of splenocytes into cells producing Th2 cytokine. Reduction in this Th2 response reduces the vasoregulatory effects of allogeneic ECs after injury.
Authors: R Ganschow; D C Broering; D Nolkemper; J Albani; M J Kemper; X Rogiers; M Burdelski Journal: Transplantation Date: 2001-09-15 Impact factor: 4.939
Authors: Joana E Kist-van Holthe; Martin Gasser; Karl Womer; Nader Najafian; Victor Dong; Dimitry V Samsonov; Chris S Geehan; Anil Chandraker; Mohamed H Sayegh; Ana Maria Waaga Journal: Kidney Int Date: 2002-08 Impact factor: 10.612
Authors: Karla Lehle; Stephan Schreml; Leoni A Kunz-Schughart; Leopold Rupprecht; Dietrich E Birnbaum; Christof Schmid; Jürgen G Preuner Journal: J Vasc Res Date: 2008-03-04 Impact factor: 1.934