Abstract 35: Transplantation of Mesenchymal Stem Cells into the Renal Medulla Attenuated Salt-sensitive Hypertension in Dahl S Rat

Transplantation of mesenchymal stem cells (MSCs) has been employed as a therapeutic strategy for many different diseases. We have recently shown that there is a stem cell dysfunction in the renal medulla that may contribute to the development of salt-sensitive hypertension in Dahl S rats. The present study tested the hypothesis that transplantation of MSCs into the renal medulla improves salt-sensitive hypertension in Dahl S rats. Rat adult MSCs were obtained from Texas A&M Health Science Center, ex-vivo expanded and infused (5 million cells) into the renal medulla in uninephrectomized Dahl S rats, which were then treated with low salt (LS, 0.4% NaCl) or high salt (HS, 8% NaCl) diet for 10 days. Results showed that the mRNA levels of stem cell markers CD133 and CD90 were increased by 60% and 70%, respectively, in the renal medulla in MSC-treated rats compared with control cell-treated rats. HS challenge increased mean arterial blood pressure in control cell-treated animals (from 113.9 ± 3.4 to 153.5 ± 4.8 mmHg), which was significantly attenuated in MSC-treated animals (from 114.1 ± 3.5 to 131.3 ± 2.5 mmHg). Meanwhile, ELISA analysis showed that the levels of pro-inflammatory cytokine interleukin-1β in the renal medulla were remarkably increased in HS-treated rats compared with LS-treated rats, which was blocked in MSC-treated rats (1.81 ± 0.18 ng/mg protein in LS group, 2.84 ± 0.57 in HS +control cell and 1.83 ± 0.35 in HS+MSC). Furthermore, immunostaining showed that the significant increase in immune cell (CD43+) infiltration into the renal medulla in HS control rats was reduced in HS+MSC rats. These results suggest that correction of stem cell dysfunction in the renal medulla attenuated inflammation in this kidney region after HS challenge and improved high salt-induced hypertension in Dahls S rats, which may serve as a therapeutic approach for salt-sensitive hypertension (supported by NIH grant HL89563 and HL106042)