Therapeutic potential of conditioned medium obtained from deferoxamine preconditioned umbilical cord mesenchymal stem cells on diabetic nephropathy model

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Ozkan S., Isildar B., Ercin M., Gezginci-Oktayoglu S., Konukoglu D., Neşetoğlu N., ...More

Stem Cell Research and Therapy, vol.13, no.1, 2022 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 13 Issue: 1
  • Publication Date: 2022
  • Doi Number: 10.1186/s13287-022-03121-6
  • Journal Name: Stem Cell Research and Therapy
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, MEDLINE, Directory of Open Access Journals
  • Keywords: Conditioned medium, Deferoxamine, Diabetic nephropathy, Mesenchymal stem cell, Preconditioning
  • Istanbul University Affiliated: Yes


© 2022, The Author(s).Background: The therapeutic potential of mesenchymal stem cells (MSCs)-derived conditioned media (CM) can be increased after preconditioning with various chemical agents. The aim of this study is comparative evaluation of effects of N-CM and DFS-CM which are collected from normal (N) and deferoxamine (DFS) preconditioned umbilical cord-derived MSCs on rat diabetic nephropathy (DN) model. Methods: After incubation of the MSCs in serum-free medium with/without 150 µM DFS for 48 h, the contents of N-CM and DFS-CM were analyzed by enzyme-linked immunosorbent assay. Diabetes (D) was induced by single dose of 55 mg/kg streptozotocin. Therapeutic effects of CMs were evaluated by biochemical, physical, histopathological and immunohistochemical analysis. Results: The concentrations of vascular endothelial growth factor alpha, nerve growth factor and glial-derived neurotrophic factor in DFS-CM increased, while one of brain-derived neurotrophic factor decreased in comparison with N-CM. The creatinine clearance rate increased significantly in both treatment groups, while the improvement in albumin/creatinine ratio and renal mass index values were only significant for D + DFS-CM group. Light and electron microscopic deteriorations and loss of podocytes-specific nephrin and Wilms tumor-1 (WT-1) expressions were significantly restored in both treatment groups. Tubular beclin-1 expression was significantly increased for DN group, but it decreased in both treatment groups. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cell death increased in the tubules of D group, while it was only significantly decreased for D + DFS-CM group. Conclusions: DFS-CM can be more effective in the treatment of DN by reducing podocyte damage and tubular apoptotic cell death and regulating autophagic activity with its more concentrated secretome content than N-CM. Graphical Abstract: [Figure not available: see fulltext.]