Endogenous stem cell mobilization versus exogenous stem cell therapy in rat model of chronic kidney disease Chronic kidney disease (CKD) affects 14% of the world population and is still a major health problem despite advances in renal transplantation. Adipose-derived mesenchymal stem cells (AD-MSCs) can restore damaged renal cells, while granulocyte colony-stimulating factor (G-CSF) is known to mobilize hematopoietic stem cells from bone marrow to peripheral circulation. The aim of this study is to compare the effect of endogenous CD34+ cell mobilization with exogenous AD-MSCs administration in the treatment of a rat model of CKD, induced by a single IV injection of ADR at a dose of 5 mg/kg. Forty eight male albino Sprague Dawley rats were divided into 4 equal groups. GI: control negative, GII: control positive, GIII: rats received 2×106 iron-labeled AD-MSCs IV on day 5 after ADR injection, and GIV received SC injection of G-CSF for 5 consecutive days at a dose of 70 μg/kg. In each group, 6 rats were sacrificed after 28 days and the other 6 after 84 days. Renal functions were assessed by measuring serum creatinine, albumin, urea and 24-hour urinary protein level at days 0, 5, 28 and 84. HB level was measured at days 0 & 84. Oxidative stress markers malondialdehyde (MDA) and total anti-oxidant (TAO) were measured, in kidney tissue, at day 28. CD 34+ cells % was measured in peripheral blood at day 9 using flowcytometry and showed a marked increase in GIV compared to other groups. After scarification, kidneys were removed for histopathological assessment. Data are expressed as means + SD and compared by ANOVA. Results revealed that both ADSCs and G-CSF significantly and similarly improved the following parameters of renal function at day 84 (p< 0.05): serum creatinine was 0.48±0.08 & 0.48±0.08 mg/dl in GIII & GIV respectively compared to 0.74±0.09 mg/dl in GII, albumin was 3.84±0.25 & 3.98±0.29 gm/dl in GIII & GIV respectively compared to 2.2±0.2 gm/dl in G II, urea was 38.4±4.10, 41.0±6.04 mg/dl in GIII & GIV respectively compared to 80.40±6.11 mg/dl in GII, and 24-hour urinary protein level was 982±77.85 & 815.80±81.11 mg in GIII & GIV respectively compared to 2841.20 ±461.85 mg in GII. HB was 14.10±0.55, 14.90±0.74 gm/dl in GIII, GIV respectively compared to 11.50±0.5 gm/ dl in GII. Comparing GIII & GIV, using post-hoc tukey test, G-CSF treated group had less 24-hour urinary protein level and higher serum albumin (p< 0.05). Homing of iron labeled AD-MSCs was microscopically detected in kidney sections. MDA level were less in groups GIII 1.56±0.21 & GIV 1.48±0.19 compared to GII 2.28±0.08 U/mg kidney tissue (P<0.05). TAO level was significantly higher in GIII & GIV (48.40±8.62 & 40.63±11.09 U/mg kidney tissue respectively) compared to GII (18.20±1.68 U/mg kidney tissue) (P<0.05). We concluded that both stimulating endogenous hematopoietic stem cells by G-CSF is at least as effective therapeutic line as injecting exogenous ADSCs in CKD.
Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, PC204
Poster Communications: Endogenous stem cell mobilization versus exogenous stem cell therapy in rat model of chronic kidney disease
Y. M. ELWAZIR1, S. Morsy1, M. Farouk1, M. Abdo1
1. Medical Physiology, Suez Canal University, Ismailia, Ismailia, Egypt.
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Where applicable, experiments conform with Society ethical requirements.