Hydrogel-Mediated Local Delivery of Induced Nephron Progenitor Cell-Sourced Molecules as a Cell-Free Approach for Acute Kidney Injury

Int J Mol Sci. 2024 Oct 2;25(19):10615. doi: 10.3390/ijms251910615.

Abstract

Acute kidney injury (AKI) constitutes a severe condition characterized by a sudden decrease in kidney function. Utilizing lineage-restricted stem/progenitor cells, directly reprogrammed from somatic cells, is a promising therapeutic option in personalized medicine for serious and incurable diseases such as AKI. The present study describes the therapeutic potential of induced nephron progenitor cell-sourced molecules (iNPC-SMs) as a cell-free strategy against cisplatin (CP)-induced nephrotoxicity, employing hyaluronic acid (HA) hydrogel-mediated local delivery to minimize systemic leakage and degradation. iNPC-SMs exhibited anti-apoptotic effects on HK-2 cells by inhibiting CP-induced ROS generation. Additionally, the localized biodistribution facilitated by hydrogel-mediated iNPC-SM delivery contributed to enhanced renal function, anti-inflammatory response, and renal regeneration in AKI mice. This study could serve as a 'proof of concept' for injectable hydrogel-mediated iNPC-SM delivery in AKI and as a model for further exploration of the development of cell-free regenerative medicine strategies.

Keywords: cell-free regenerative medicine; induced nephron progenitor cells; injectable hydrogel.

MeSH terms

  • Acute Kidney Injury*
  • Animals
  • Apoptosis / drug effects
  • Cell Line
  • Cell-Free System
  • Cisplatin / administration & dosage
  • Disease Models, Animal
  • Humans
  • Hyaluronic Acid / administration & dosage
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology
  • Hydrogels* / chemistry
  • Male
  • Mice
  • Nephrons* / drug effects
  • Nephrons* / metabolism
  • Reactive Oxygen Species / metabolism
  • Regeneration
  • Stem Cells* / cytology
  • Stem Cells* / metabolism

Substances

  • Hydrogels
  • Hyaluronic Acid
  • Cisplatin
  • Reactive Oxygen Species