Effects of High Glucose Concentration on Pericyte-Like Differentiated Human Adipose-Derived Mesenchymal Stem Cells.
Giuliana ManninoAnna LongoFlorinda GennusoCarmelina Daniela AnfusoGabriella LupoGiovanni GiurdanellaRosario GiuffridaDebora Lo FurnoPublished in: International journal of molecular sciences (2021)
A pericyte-like differentiation of human adipose-derived mesenchymal stem cells (ASCs) was tested in in vitro experiments for possible therapeutic applications in cases of diabetic retinopathy (DR) to replace irreversibly lost pericytes. For this purpose, pericyte-like ASCs were obtained after their growth in a specific pericyte medium. They were then cultured in high glucose conditions to mimic the altered microenvironment of a diabetic eye. Several parameters were monitored, especially those particularly affected by disease progression: cell proliferation, viability and migration ability; reactive oxygen species (ROS) production; inflammation-related cytokines and angiogenic factors. Overall, encouraging results were obtained. In fact, even after glucose addition, ASCs pre-cultured in the pericyte medium (pmASCs) showed high proliferation rate, viability and migration ability. A considerable increase in mRNA expression levels of the anti-inflammatory cytokines transforming growth factor-β1 (TGF-β1) and interleukin-10 (IL-10) was observed, associated with reduction in ROS production, and mRNA expression of pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and angiogenic factors. Finally, a pmASC-induced better organization of tube-like formation by retinal endothelial cells was observed in three-dimensional co-culture. The pericyte-like ASCs obtained in these experiments represent a valuable tool for the treatment of retinal damages occurring in diabetic patients.
Keyphrases
- endothelial cells
- high glucose
- blood brain barrier
- diabetic retinopathy
- transforming growth factor
- reactive oxygen species
- optical coherence tomography
- cell proliferation
- vascular endothelial growth factor
- epithelial mesenchymal transition
- dna damage
- rheumatoid arthritis
- cell death
- adipose tissue
- stem cells
- type diabetes
- oxidative stress
- insulin resistance
- metabolic syndrome
- skeletal muscle
- wound healing