Conditioned Medium from Human Uterine Cervical Stem Cells Regulates Oxidative Stress and Angiogenesis of Retinal Pigment Epithelial Cells

Ophthalmic Res. 2022;65(5):556-565. doi: 10.1159/000524484. Epub 2022 May 18.

Abstract

Introduction: Retinal homeostasis is essential to avoid retinal pigment epithelium (RPE) damage resulting in photoreceptor death and blindness. Mesenchymal stem cells-based cell therapy could contribute to the maintenance of the retinal homeostasis. We have explored the effect of human uterine cervical stem cells (hUCESCs)-conditioned medium (hUCESC-CM) on RPE cells under oxidative stress condition.

Methods: ARPE-19 cells were treated with hydrogen peroxide (H2O2) in the presence or absence of hUCESC-CM. qRT-PCR and Western blot were used to evaluate the expression of oxidative stress-related (HO-1, GCLC, and HSPB1) and vasculogenesis-related (VEGFA, PDGFA, and PDGFB) factors. Also, we assessed in vitro effects of hUCESC-CM on endothelial-cell (HUVEC) tube formation.

Results: mRNA expression of HO-1, GCLC, HSPB1, VEGFA, PDGFA, and PDGFB were significantly increased in ARPE-19 cells treated with H2O2 + hUCESC-CM compared to cells treated with H2O2 only. Regarding the tube formation assay, HUVEC treated with supernatant from ARPE-19 cells treated with H2O2 + hUCESC-CM showed a significant increase in average vessel length, number of capillary-like junctions, and average of vessels area compared with HUVEC treated with supernatant from ARPE-19 cells treated with H2O2 only.

Conclusion: Our results show potential therapeutic effects of hUCESC-CM on RPE, such as protection from damage by oxidative stress, stimulation of detoxifying genes, and a better vascularization.

Keywords: Angiogenesis; Conditioned medium; Human uterine cervical stem cells; Mesenchymal stem cells; Oxidative stress; Retinal pigment epithelium; Secretome.

MeSH terms

  • Cell Survival
  • Culture Media, Conditioned / metabolism
  • Culture Media, Conditioned / pharmacology
  • Endothelial Cells / metabolism
  • Epithelial Cells / metabolism
  • Humans
  • Hydrogen Peroxide* / toxicity
  • Neovascularization, Pathologic / metabolism
  • Oxidative Stress*
  • Proto-Oncogene Proteins c-sis / metabolism
  • Proto-Oncogene Proteins c-sis / pharmacology
  • RNA, Messenger / metabolism
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigments / metabolism
  • Stem Cells

Substances

  • Culture Media, Conditioned
  • Proto-Oncogene Proteins c-sis
  • RNA, Messenger
  • Retinal Pigments
  • Hydrogen Peroxide