CELL THERAPY USING MSCS AND BMDCS IN RAT KIDNEY TRANSPLANTATION

CELL THERAPY AND STEM CELLS

M. Franquesa¹, M. Flaquer², J.M. Cruzado³, J. Torras³, J. Grinyo³, I. Herrero-fresneda^2
1Experimental Nephrology-lab 4122, IDIBELL, L'Hospitalet de Llobregat/SPAIN, ²Experimental Nephrology-4122, IDIBELL, L'Hospitalet de Llobregat/SPAIN, ³, Hospital de Bellvitge, Hospitalet de llobregat/SPAIN

Body: Hypothesis: we hypothesized that in a rat model of Chronic transplant Nephropathy (CTN) exogenous administration of Mesenchymal Stem Cells (MSCs) at 12 weeks would ameliorate renal function antagonizing tissue fibrosis mechanisms and fostering regeneration diminishing the characteristic features of CTN. Around 12 weeks post-Tx is a critical moment for allografts as the fibrotic characteristic features of CTN start to develop with an increasing proteinuria. Methods: To assess this hypothesis we designed the present study using the CAN model where Fischer kidneys were preserved for 2 hours and a half in EC solution at 4ºC and transplanted into Lewis rats Right native nephrectomy was performed at the same day of Transtplantation and all rats received a single oral dose of Cyclosporin 5 mg/Kg daily for the first 15 days post-Tx. For renal function assessment, serum creatinine (Cr,mmol/l) and proteinuria (Prot, mg/24h) were determined every 4 weeks for 24 weeks. Bone marrow PBMCs were isolated from femurs and tibias of GFP+ rats. Bones were flushed with PBS. MSCs were isolated by their plastic adherence properties in 15cm diameter plates and expanded in DMEM+10%FBS. CD45-CD11b/c positive cells were depleted and negative fraction was confirmed to be CD90+ MSCs. Groups: transplanted animals received a single injection through the tail vein between 10 and 12weeks post-Tx PBS: Sham injection BMDCs: 10⁷ bone marrow PBMCs MSCs: 5·10⁵ bone marrow derived MSCs Results: Animals that received either MSCs or BMDCs showed better graft function evaluated by serum Creatinine determinations and Proteinuria (Table1).

	Serum Creatinine			Proteinuria
	16w	20w	24w	16w	20w	24w
PBS	84,6±9,9	100,9±15,9	109,5±24,8	25,1±8,6	44,8±19,3	67,8±32,4
BMDCs	62,9±2,5 a	68,4±2,8 a	65,9±2,29a	16,9±0,9	17,4±1,7	26,1±3,4 a
MSCs	63,4±2,23a	61,2±1,13a	59,9±2,3a	15,01±1,7	15,7±1,6	18,7±2,6 a

a: p≤0,025 vs control (PBS) Conclusions: As expected non-treated transplanted animals developed renal insufiency and progressive proteinuria. Cell therapy with MSCs or BMDCs injected between 10 and 12 weeks protected from those fibrotic features.

Disclosure: All authors have declared no conflicts of interest.