Abstract: SA-PO379

Modulation of Podocyte (PD) Homeostasis by Mesenchymal Stromal Bone Marrow Cells (MS-BMC) in the Adriamycin Two and Single Kidney Injury Models

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 301 CKD: Risk Factors for Incidence and Progression

Authors

  • Aslam, Rukhsana, Feinstein Institute for medical research, Glenoaks, New York, United States
  • Hussain, Ali, Feinstein Institute of Medical Research, New York, New York, United States
  • Marashi Shoshtari, Seyedeh Shadafarin, The Feinstein Institute for Medical Research, Manhasset, New York, United States
  • Mishra, Abheepsa, Feinstein Institute of Medical Research, Northwell Health, MANHASSET, New York, United States
  • Kumar, Vinod, Fienstine Institute for Medical Research, New York, New York, United States
  • Malhotra, Ashwani, Feinstein Inst.Med research and NSLIJ, Manhasset, New York, United States
  • Singhal, Pravin C., North Shore LIJ Health System, Great Neck, New York, United States
Background

Adriamycin has been demonstrated to induce focal segmental glomerulosclerosis (FSGS). Mesenchymal stromal bone marrow cells (MS-BMCs) have been demonstrated to provide cytoprotection by the modulation of cytokine production in several nephrotoxic models. Recently, parietal epithelial cells (PECS) have been considered as progenitor cells to manage podocyte homeostasis; however, PECs may also act as profibrotic cells in adverse milieus. In the present study, we evaluated the effect of MS-BMCs on modulation of the role of parietal epithelial cells in mananging the podocyte homeostasis in adriamycin-induced podocyte injury in two and single kidney injury models.

Methods

MS-BMCs were harvested from bone marrows of mice and their profile was characterized. Mice in groups of six were administered either buffer (group A), intracapsular instillation of MS-BMCs in left kidney (group B), or intraperitoneal MS-BMCs administration (Group C) 24 hours prior to Adriamycin (150 mg/Kg, subcutaneously) administration. Additional six mice administered normal saline were used as controls. All mice were euthanized after 4 weeks; urine and blood samples were collected for BUN and albumin: creatinine ratio. Kidneys were harvested for histology, immuno-staining for p57 and co-labeling for CD44 and phospho-ERK. Immunoblots were prepared and probed for podocin and WT1 and reprobed for actin.

Results

Group B and C mice displayed a decrease (P<0.05) in albumin: creatinine ratio vs. Group A mice. Immunoblotting studies revealed decreased (P<0.01) podocin, WT1, and p57 expressions in renal tissues of group C when compared to renal tissues of group A. On the other hand, renal tissues of the left kidneys from Group B displayed increased (P<0.01) protein expression of podocin, WT1, and p57 when compared to contralateral kidneys. Kidneys from the group C and right kidneys from the group B displayed increased (P<0.05) number of profibrotic cells (colabeled for phos-ERK and CD44) but a decreased (P<0.05) number of p57 +ve cells.

Conclusion

These findings indicate that MS-BMCs provide protection from injurious effect of adriamycin by decreasing the number of pro-fibrotic PECs and increasin the number of progentor cells.

Funding

  • NIDDK Support