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Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review)

  • Authors:
    • Yuanxia Zou
    • Jian Dai
    • Jingyuan Fu
    • Honglian Wang
    • Meng Yang
    • Jiraporn Kantapan
    • Li Wang
    • Nathupakorn Dechsupa
  • View Affiliations / Copyright

    Affiliations: Research Center for Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Neurology, The Third People's Hospital of Luzhou, Luzhou, Sichuan 646000, P.R. China, Department of Neonatal Intensive Care Unit, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610075, P.R. China, Department of Children's Diagnosis and Treatment Center, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Molecular Imaging and Therapy Research Unit, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50000, Thailand
    Copyright: © Zou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 179
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    Published online on: September 1, 2025
       https://doi.org/10.3892/ijmm.2025.5620
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Abstract

Acute kidney injury (AKI) remains a significant clinical challenge, characterized by rapid kidney dysfunction with potential progression to chronic kidney disease. Mesenchymal stem cells (MSCs) offer promising therapeutic potential due to their regenerative, immunomodulatory and anti‑inflammatory capabilities. Despite these advantages, clinical translation is hampered by low MSCs retention, limited cell survival and suboptimal secretion of therapeutic factors in injured renal tissues. Recent research efforts have introduced innovative strategies to optimize MSCs effectiveness, including various preconditioning approaches (hypoxia, chemical/drug‑based and biological cytokines), advanced three‑dimensional cell culture methods (hydrogels and spheroids), genetic modification techniques and improved delivery routes. The present review summarizes current advancements, underlying mechanisms and therapeutic outcomes associated with these novel strategies to enhance MSCs efficacy in AKI, highlighting their clinical potential and guiding future translational research directions.
View Figures

Figure 1

Mechanisms underlying MSC-mediated
renal repair in AKI. MSCs derived from various sources and
facilitate renal repair through multiple intercellular
communication pathways. These include (1) mitochondrial transfer via TNTs,
(2) direct cell fusion,
(3) secretion of extracellular
vesicles such as exosomes and microvesicles containing miRNA,
cytokines, mitochondria and therapeutic drugs and (4) gap junction-mediated transfer of
signaling molecules via connexins. These mechanisms collectively
contribute to promoting renal progenitor/stem cell activation,
reducing apoptosis of tubular epithelial cells, shifting macrophage
polarization from the pro-inflammatory M1 to anti-inflammatory M2
phenotype and inhibiting T-cell and dendritic cell-mediated immune
responses. Consequently, MSCs markedly enhance renal regeneration,
facilitating the repair and functional recovery of injured kidneys
in AKI. MSCs, mesenchymal stem cells; AKI, acute kidney injury;
TNTs, tunneling nanotubes; BMSCs, bone mesenchymal stem cells;
ADMSCs, adipose-derived mesenchymal stem cells; hpMSCs, human
placenta-derived mesenchymal stem cells; WJMSCs, Wharton's
jelly-derived mesenchymal stem cells; UCMSCs, umbilical cord
mesenchymal stem cells.

Figure 2

Different preconditioned MSCs
strategies. This figure summarizes the current preconditioned
methods for MSCs. These strategies include changing the culture
environment, drugs treatment, chemical stimulation, biological
compounds preconditioning, cell-to-cell coculture and genetic
modification, all aimed at enhancing their biological
characteristics and therapeutic effects. MSCs, mesenchymal stem
cells.

Figure 3

Delivery routes and adjuvant
strategies for MSC-based therapy in AKI models. Multiple
administration routes have been explored to enhance the therapeutic
efficacy of MSCs in AKI. Systemic injection methods include IV, IP
and (IA) delivery, allowing widespread cell distribution. Local
injection approaches, such as SC, IR and RA routes, facilitate
direct cell delivery to the injured kidney, improving targeting
efficiency. Adjuvant methods, including PFUS, biomaterials and cell
sheet engineering, are employed to enhance MSCs retention,
viability and therapeutic function at the injury site. These
strategies aim to overcome challenges such as poor engraftment,
limited homing and transient efficacy of transplanted MSCs in AKI.
MSCs, mesenchymal stem cells; AKI, acute kidney injury; IV,
intravenous; IP, intraperitoneal; IA, intra-arterial; SC,
subcapsular; IR, intrarenal; RA, renal arterial; PFUS, pulsed
focused ultrasound.
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Copy and paste a formatted citation
Spandidos Publications style
Zou Y, Dai J, Fu J, Wang H, Yang M, Kantapan J, Wang L and Dechsupa N: Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review). Int J Mol Med 56: 179, 2025.
APA
Zou, Y., Dai, J., Fu, J., Wang, H., Yang, M., Kantapan, J. ... Dechsupa, N. (2025). Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review). International Journal of Molecular Medicine, 56, 179. https://doi.org/10.3892/ijmm.2025.5620
MLA
Zou, Y., Dai, J., Fu, J., Wang, H., Yang, M., Kantapan, J., Wang, L., Dechsupa, N."Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review)". International Journal of Molecular Medicine 56.5 (2025): 179.
Chicago
Zou, Y., Dai, J., Fu, J., Wang, H., Yang, M., Kantapan, J., Wang, L., Dechsupa, N."Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 179. https://doi.org/10.3892/ijmm.2025.5620
Copy and paste a formatted citation
x
Spandidos Publications style
Zou Y, Dai J, Fu J, Wang H, Yang M, Kantapan J, Wang L and Dechsupa N: Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review). Int J Mol Med 56: 179, 2025.
APA
Zou, Y., Dai, J., Fu, J., Wang, H., Yang, M., Kantapan, J. ... Dechsupa, N. (2025). Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review). International Journal of Molecular Medicine, 56, 179. https://doi.org/10.3892/ijmm.2025.5620
MLA
Zou, Y., Dai, J., Fu, J., Wang, H., Yang, M., Kantapan, J., Wang, L., Dechsupa, N."Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review)". International Journal of Molecular Medicine 56.5 (2025): 179.
Chicago
Zou, Y., Dai, J., Fu, J., Wang, H., Yang, M., Kantapan, J., Wang, L., Dechsupa, N."Innovative strategies to enhance MSCs efficacy in acute kidney injury (Review)". International Journal of Molecular Medicine 56, no. 5 (2025): 179. https://doi.org/10.3892/ijmm.2025.5620
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