Human amniotic epithelial derived stem cells attenuate anti-myeloperoxidase glomerulonephritis.

Aim: To determine whether human amniotic epithelial stem cells (hAECs) can attenuate autoimmune anti-myeloperoxidase (MPO) glomerulonephritis. Background(s): hAECs are characteristically pluripotent, with low antigenicity and are highly anti-inflammatory, making them an attractive stem cell based therapeutic. Their use in anti-MPO glomerulonephritis has not been explored. Method(s): Anti-MPO glomerulonephritis was induced by immunisation with MPO/adjuvant (day [d] 0, 7) followed by disease trigger using low dose antiglomerular basement membrane globulin (d16). hAECs or vehicle were administered either 3d before each MPO/adjuvant injection or just before disease trigger (d14) and their effects on anti-MPO autoimmunity and GN assessed. hAECs were also co-cultured with splenocytes from MPO-immunised animals and their effect on MPO-specific T cell responses measured. Result(s): hAECs suppressed MPO-specific T cell responses when co-cultured with splenocytes in vitro (2.7 +/- 0.6 vs 7.5 +/- 0.8% bromodeoxyuridine+CD4+ cells, p < 0.01). In vivo, when used as a preventative, hAECs attenuated MPO-specific dermal delayed-type hypersensitivity (DTH; 0.1 +/- 0.03 vs 0.5 +/- 0.DELTAmm, p < 0.05), while enhancing proliferation of foxp3+CD25+ regulatory T cells (1.20 +/- 0.09 vs 0.84 +/- 0.13%, p < 0.05), CD4+ IL-10 producing cells (0.05 +/- 0.01 vs 0.26 +/- 0.09% p < 0.05) and surface expression of indoleamine 2,3 dioxygenase+ (0.027 +/- 0.004 vs 0.28 +/- 0.08%, p < 0.05), without affecting dendritic cells. Therapeutic administration of hAECs attenuated the development of glomerulonephritis (segmental necrosis: 15.6 +/- 2.2 vs 40.6 +/- 2.2%, p < 0.05), correlating with reduced accumulation of macrophages (0.2 +/- 0.04 vs 0.4 +/- 0.06 cells/ glomerular cross section [c/gcs], p < 0.05), CD4+ cells (0.3 +/- 0.03 vs 0.4 +/- 0.05 c/ gcs, p < 0.05) and neutrophils (0.2 +/- 0.03 vs 0.4 +/- 0.03 c/gcs, p < 0.01). Systemic anti-MPO autoimmunity was also reduced (DTH: 0.01 +/- 0.01 vs 0.4