Adipose-derived mesenchymal stromal cell secretome protects against kidney injury through induction of heme oxygenase 1 upregulation in vitro

doi:10.5527/wjn.v14.i3.108534

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World Journal of Nephrology

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World J Nephrol. Sep 25, 2025; 14(3): 108534
Published online Sep 25, 2025. doi: 10.5527/wjn.v14.i3.108534

Adipose-derived mesenchymal stromal cell secretome protects against kidney injury through induction of heme oxygenase 1 upregulation in vitro

Hanan Jafar, Nidaa A Ababneh, Dana Alhattab, Renata M Alatoom, Suzan Zalloum, Bareqa Salah, Hussein Alhawari, Abdalla Awidi

Hanan Jafar, Nidaa A Ababneh, Renata M Alatoom, Suzan Zalloum, Abdalla Awidi, Cell Therapy Center, The University of Jordan, Amman 11942, Jordan

Dana Alhattab, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia

Dana Alhattab, KAUST Center of Excellence for Smart Health, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia

Bareqa Salah, Hussein Alhawari, Abdalla Awidi, School of Medicine, The University of Jordan, Amman 11942, Jordan

Bareqa Salah, Department of General Surgery, Jordan University Hospital, Amman 11942, Jordan

Hussein Alhawari, Abdalla Awidi, Department of Internal Medicine, Jordan University Hospital, Amman 11942, Jordan

Co-corresponding authors: Nidaa A Ababneh and Abdalla Awidi.

Author contributions: Jafar H, Ababneh NA, and Awidi A conceived the study and prepared the methodology; Jafar H and Ababneh NA performed the formal analyses, and wrote the manuscript; Jafar H and Awidi A secured the funding, and reviewed the manuscript; Alhattab D performed data the curation and visualization; Alatoom RM and Zalloum S performed the experiments; Salah B and Alhawari H performed the clinical methods and provided resources; Ababneh NA and Awidi A supervised the work; All authors have read and approved the final manuscript. The two co-corresponding authors made equal contributions to the conception, supervision, and administration of this work. Both authors jointly worked on the experimental design, data interpretation, and manuscript preparation, and will continue to share responsibility for post-publication inquiries.

Supported by Abdul Hameed Shoman Foundation, No. 6/2018.

Institutional review board statement: All subjects had signed written informed consents before participation in the study, which was approved by the Institutional Review Board ( approval number IRB-CTC-1-2022-08) at the Cell Therapy Center adhering to the ethical guidelines of the Declaration of Helsinki.

Conflict-of-interest statement: The authors have no relevant financial or non-financial interests to disclose.

Data sharing statement: All data generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Corresponding author: Abdalla Awidi, Cell Therapy Center, The University of Jordan, Queen Rania St, Amman 11942, Amman, Jordan. aabbadi@ju.edu.jo

Received: April 17, 2025
Revised: May 29, 2025
Accepted: July 15, 2025
Published online: September 25, 2025
Processing time: 153 Days and 22.7 Hours

Abstract

BACKGROUND

Acute kidney injury is characterized by a sudden decline in renal function, often due to ischemia or nephrotoxins, leading to increased oxidative stress and inflammation.

AIM

To investigate the protective effects of adipose-derived mesenchymal stromal cell (ADMSC) secretome on renal tubular epithelial cells (NRK-52E) as an in vitro model of oxidative stress-associated kidney injury.

METHODS

ADMSCs were isolated from human adipose tissue and characterized for mesenchymal markers and differentiation potential. Conditioned media (CM) was collected after 48-hour serum-free culture and applied to serum-deprived NRK-52E cells for 48 hours. Cell viability was assessed using the MTT assay, apoptosis was assessed by Annexin V-FITC/PI staining and flow cytometry, reactive oxygen species (ROS) levels via H2DCFDA staining, and mitochondrial membrane potential by the tetramethylrhodamine ethyl ester assay. The expression of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and NAD(P)H quinone dehydrogenase 1 (Nqo1) genes was quantified by quantitative polymerase chain reaction. Comparative transcriptomic analysis was performed on ADMSCs and bone marrow-derived MSCs (BM-MSCs) using publicly available microarray data (GSE108511).

RESULTS

ADMSC secretome significantly reduced ROS production and enhanced mitochondrial membrane potential in NRK cells. Gene expression analysis revealed a significant upregulation of HO-1 mRNA levels in ADMSC-CM treated cells. However, no significant changes were observed in Nrf2 and Nqo1 mRNA levels. Transcriptome analysis of ADMSCs against BM-MSCs revealed significant differences in the expression of genes related to oxidative stress response, antioxidant activity, and mitochondrial function.

CONCLUSION

The results of this study suggest that the ADMSC secretome exerts multifaceted protective effects on NRK cells by reducing oxidative stress and enhancing mitochondrial function. The study demonstrates the potential beneficial applications of the ADMSC secretome in treating oxidative stress-related kidney injuries.

Keywords: Renal tubular epithelial cells; Secretome; Heme oxygenase 1 upregulation; Oxidative stress; Mesenchymal stromal cells; Acute kidney injury

Core Tip: This study highlights the therapeutic potential of secretome derived from adipose-derived mesenchymal stromal cells (ADMSCs) in protecting renal tubular epithelial cells under oxidative stress conditions. The ADMSC secretome reduced reactive oxygen species levels, enhanced mitochondrial membrane potential, and upregulated heme oxygenase 1 gene expression, indicating activation of cytoprotective pathways. Comparative transcriptome analysis with bone marrow-derived mesenchymal stromal cells revealed distinct gene expression profiles related to mitochondrial and antioxidant functions. These findings support the use of ADMSC secretome as a promising cell-free approach for mitigating oxidative damage in acute kidney injury.