Potential Therapeutic Effects of Long-Term Stem Cell Administration: Impact on the Gene Profile and Kidney Function of PKD/Mhm (Cy/+) Rats

Daniela Nardozi; Stefania Palumbo; Arif Ul Maula Khan; Carsten Sticht; Karen Bieback; Samar Sadeghi; Mark Andreas Kluth; Michael Keese; Norbert Gretz

doi:10.3390/jcm11092601

Potential Therapeutic Effects of Long-Term Stem Cell Administration: Impact on the Gene Profile and Kidney Function of PKD/Mhm (Cy/+) Rats

J Clin Med. 2022 May 5;11(9):2601. doi: 10.3390/jcm11092601.

Authors

Daniela Nardozi^{1

2}, Stefania Palumbo¹, Arif Ul Maula Khan¹, Carsten Sticht¹, Karen Bieback³, Samar Sadeghi⁴, Mark Andreas Kluth⁴, Michael Keese², Norbert Gretz¹

Affiliations

¹ Medical Research Center, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, 68167 Mannheim, Germany.
² Vascular Surgery, University Hospital Mannheim, 68167 Mannheim, Germany.
³ Institute of Transfusion Medicine and Immunology, Mannheim Institute of Innate Immunoscience, German Red Cross Blood Service Baden-Württemberg-Hessen, Medical Faculty Mannheim, Heidelberg University, 68167 Mannheim, Germany.
⁴ RHEACELL GmbH & Co.KG/TICEBA GmbH, 69120 Heidelberg, Germany.

Abstract

Cystic kidney disease (CKD) is a heterogeneous group of genetic disorders and one of the most common causes of end-stage renal disease. Here, we investigate the potential effects of long-term human stem cell treatment on kidney function and the gene expression profile of PKD/Mhm (Cy/+) rats. Human adipose-derived stromal cells (ASC) and human skin-derived ABCB5⁺ stromal cells (2 × 10⁶) were infused intravenously or intraperitoneally monthly, over 6 months. Additionally, ASC and ABCB5⁺-derived conditioned media were administrated intraperitoneally. The gene expression profile results showed a significant reprogramming of metabolism-related pathways along with downregulation of the cAMP, NF-kB and apoptosis pathways. During the experimental period, we measured the principal renal parameters as well as renal function using an innovative non-invasive transcutaneous device. All together, these analyses show a moderate amelioration of renal function in the ABCB5⁺ and ASC-treated groups. Additionally, ABCB5⁺ and ASC-derived conditioned media treatments lead to milder but still promising improvements. Even though further analyses have to be performed, the preliminary results obtained in this study can lay the foundations for a novel therapeutic approach with the application of cell-based therapy in CKD.

Keywords: ABCB5; adipose-derived stromal cell (ASC); conditioned media; cystic kidney disease (CKD); gene expression profile.

Grants and funding

This research received external funding by the Land Baden-Württemberg: Cooperative Research Training Group: Tissue Analytics for Stem Cell based Diagnostics and Therapy (TASCDT) and the Bundesministerium für Bildung und Forschung (BMBF) within the Network for Early Onset Cystic Kidney Disease (NEOCYST).