2. Academic Validation
  3. Extracellular vesicles from organoid-derived human retinal progenitor cells prevent lipid overload-induced retinal pigment epithelium injury by regulating fatty acid metabolism

Extracellular vesicles from organoid-derived human retinal progenitor cells prevent lipid overload-induced retinal pigment epithelium injury by regulating fatty acid metabolism

  • J Extracell Vesicles. 2024 Jan;13(1):e12401. doi: 10.1002/jev2.12401.
Hui Gao 1 2,  Yuxiao Zeng 1 2,  Xiaona Huang 1 2,  Luodan A 1 2,  Qingle Liang 3,  Jing Xie 1 2,  Xi Lin 1 2,  Jing Gong 1 2 4,  Xiaotang Fan 5,  Ting Zou 1 2 6,  Haiwei Xu 1 2
Affiliations

Affiliations

  • 1 Southwest Eye Hospital, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • 2 Key Lab of Visual Damage and Regeneration & Restoration of Chongqing, Chongqing, China.
  • 3 Department of Clinical Laboratory Medicine, First Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
  • 4 Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China.
  • 5 Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, China.
  • 6 Department of Ophthalmology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PMID: 38151470 DOI: 10.1002/jev2.12401
Abstract

Retinal degeneration (RD), a group of diseases leading to irreversible vision loss, is characterised by retinal pigment epithelium (RPE) or retinal neuron damage and loss. With fewer risks of immune rejection and tumorigenesis, stem cell-secreted extracellular vesicles (EVs) offer a new cell-free therapeutic paradigm for RD, which remains to be investigated. Human retinal organoid-derived retinal progenitor cells (hERO-RPCs) are an easily accessible and advanced cell source for RD treatment. However, hERO-RPCs-derived EVs require further characterisation. Here, we compared the characteristics of EVs from hERO-RPCs (hRPC-EVs) with those of human embryonic stem cell (hESC)-derived EVs (hESC-EVs) as controls. Based on in-depth proteomic analysis, we revealed remarkable differences between hRPC-EVs and hESC-EVs. A comparison between EVs and their respective cells of origin demonstrated that the protein loading of hRPC-EVs was more selective than that of hESC-EVs. In particular, hESC-EVs were enriched with proteins related to angiogenesis and cell cycle, whereas hRPC-EVs were enriched with proteins associated with immune modulation and retinal development. More importantly, compared with that of hESC-EVs, hRPC-EVs exhibited a lower correlation with cell proliferation and a unique capacity to regulate lipid metabolism. It was further confirmed that hRPC-EVs potentially eliminated lipid deposits, inhibited lipotoxicity and oxidative stress, and enhanced phagocytosis and survival of oleic acid-treated ARPE-19 cells. Mechanistically, hRPC-EVs are integrated into the mitochondrial network of oleic acid-treated ARPE-19 cells, and increased the level of mitochondrial fatty acid β-oxidation-related proteins. Thus, organoid-derived hRPC-EVs represent a promising source of cell-free therapy for RD, especially for blinding diseases related to abnormal lipid metabolism in RPE cells.

Keywords

extracellular vesicles; lipid metabolism; retinal organoids; retinal pigment epithelium cells; retinal progenitor cells.

Figures
Products