Transplantation of mesenchymal stem cells preserves podocyte homeostasis through modulation of parietal epithelial cell activation in adriamycin-induced mouse kidney injury model
Rukhsana Aslam1, Ali Hussain1, Kang Cheng1, Vinod Kumar1, Ashwani Malhotra1, Sanjeev Gupta2 and Pravin C. Singhal1
1Departments of Medicine, Hofstra Northwell School of Medicine and 2Department of Medicine, Department of Pathology, Marion Bessin Liver Research Center, Diabetes Center, The Irwin S. and Sylvia Chanin Institute for Cancer Research, and Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Albert Einstein College of Medicine, New York, USA
Offprint requests to: Pravin C. Singhal, MD, Division of Kidney Diseases and Hypertension, 100 Community Drive, Great Neck, NY 11021, USA. e-mail: psinghal@northwell.edu
Summary. To determine the role of the transplantation of bone marrow-derived mesenchymal stem cells (MSCs) in podocyte renewal, we studied BALB/C mice with or without adriamycin-induced acute kidney injury. MSCs were transplanted ectopically under the capsule of the left kidney or into the peritoneal cavity after the onset of kidney injury to test their local or systemic paracrine effects, respectively. Adriamycin produced increases in urine protein: creatinine ratios, blood urea nitrogen, and blood pressure, which improved after both renal subcapsular and intraperitoneal MSCs transplants. The histological changes of adriamycin kidney changes regressed in both kidneys and in only the ipsilateral kidney after intraperitoneal or renal subcapsular transplants indicating that the benefits of transplanted MSCs were related to the extent of paracrine factor distribution. Analysis of kidney tissues for p57-positive podocytes showed that MSC transplants restored adriamycin-induced decreases in the abundance of these cells to normal levels, although after renal subcapsular transplants these changes did not extend to contralateral kidneys. Moreover, adriamycin caused inflammatory activation of PECs with coexpression of CD44 and phospho-ERK, which was normalized in both or only ipsilateral kidneys depending on whether MSCs were transplanted in the peritoneal cavity or subcapsular space, respectively. Histol Histopathol 35, 1483-1492 (2020)
Key words: Mesenchymal stem cells, Parietal epithelial cells, Podocytes, Profibrotic cells, Acute kidney injury, Chronic kidney disease
DOI: 10.14670/HH-18-276