Adipose-derived mesenchymal stromal cells reverse high glucose-induced reduction of angiogenesis in human retinal microvascular endothelial cells.
Cells, Cultured
Coculture Techniques
Culture Media, Conditioned
Diabetic Retinopathy
/ etiology
Endothelial Cells
/ metabolism
Glucose
/ metabolism
Human Umbilical Vein Endothelial Cells
Humans
Hyperglycemia
/ complications
Mesenchymal Stem Cell Transplantation
/ methods
Mesenchymal Stem Cells
/ metabolism
Neovascularization, Pathologic
/ metabolism
Pericytes
/ metabolism
Retina
/ cytology
Transfection
angiogenesis
diabetic retinopathy
hyperglycemia
mesenchymal stromal cells
reactive oxygen species
retinal endothelial cells
Journal
Cytotherapy
ISSN: 1477-2566
Titre abrégé: Cytotherapy
Pays: England
ID NLM: 100895309
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
16
12
2019
revised:
12
02
2020
accepted:
22
02
2020
pubmed:
6
4
2020
medline:
28
10
2020
entrez:
6
4
2020
Statut:
ppublish
Résumé
Diabetic retinopathy (DR) is characterized by a progressive alteration of the retinal microvasculature, arising from microaneurysms to leaky vessels and finally abnormal neovascularization. The hyperglycemia-mediated loss of pericytes is a key event in vessel degeneration causing vascular destabilization. To overcome this, mesenchymal stromal cells (MSCs) have been tested as pericyte replacement in several animal models showing repair and regeneration of DR-damaged vasculature. We hypothesized that adipose-derived mesenchymal stromal cells (ASCs) resist high glucose-induced challenges and protect human retinal microvascular endothelial cells (HRMVECs) from glucose-mediated injury. ASCs and HRMVECs were cultured under normal-glucose (NG; 1 g/L) and high-glucose (HG; 4.5 g/L) conditions comparing their phenotype and angiogenic potential. Whereas ASCs were generally unaffected by HG, HG caused a reduction of the angiogenic potential in HRMVEC. Indeed, HG-treated HRMVECs formed fewer vascular tube structures in a basement membrane angiogenesis assay. However, this was not observed in a direct ASC and HRMVEC coculture angiogenesis assay. Increased oxidative stress levels appeared to be linked to the HG-induced reduction of angiogenesis, which could be restored by ASC-conditioned medium and antioxidant treatment. These findings suggest that ASC resist HG-stress whereas endothelial cell angiogenic capacity is reduced. Thus, ASC may be potentially therapeutically active in DR by restoring angiogenic deficits in retinal endothelial cells by the secretion of proangiogenic factors. However, these data also inquire for a thorough risk assessment about the timing of the ASC-based cell therapy, which can be considered advantageous at early stage of DR, but possibly detrimental at the late neo-angiogenic stage of DR.
Sections du résumé
BACKGROUND AIMS
Diabetic retinopathy (DR) is characterized by a progressive alteration of the retinal microvasculature, arising from microaneurysms to leaky vessels and finally abnormal neovascularization. The hyperglycemia-mediated loss of pericytes is a key event in vessel degeneration causing vascular destabilization. To overcome this, mesenchymal stromal cells (MSCs) have been tested as pericyte replacement in several animal models showing repair and regeneration of DR-damaged vasculature.
METHODS
We hypothesized that adipose-derived mesenchymal stromal cells (ASCs) resist high glucose-induced challenges and protect human retinal microvascular endothelial cells (HRMVECs) from glucose-mediated injury. ASCs and HRMVECs were cultured under normal-glucose (NG; 1 g/L) and high-glucose (HG; 4.5 g/L) conditions comparing their phenotype and angiogenic potential.
RESULTS
Whereas ASCs were generally unaffected by HG, HG caused a reduction of the angiogenic potential in HRMVEC. Indeed, HG-treated HRMVECs formed fewer vascular tube structures in a basement membrane angiogenesis assay. However, this was not observed in a direct ASC and HRMVEC coculture angiogenesis assay. Increased oxidative stress levels appeared to be linked to the HG-induced reduction of angiogenesis, which could be restored by ASC-conditioned medium and antioxidant treatment.
CONCLUSIONS
These findings suggest that ASC resist HG-stress whereas endothelial cell angiogenic capacity is reduced. Thus, ASC may be potentially therapeutically active in DR by restoring angiogenic deficits in retinal endothelial cells by the secretion of proangiogenic factors. However, these data also inquire for a thorough risk assessment about the timing of the ASC-based cell therapy, which can be considered advantageous at early stage of DR, but possibly detrimental at the late neo-angiogenic stage of DR.
Identifiants
pubmed: 32247542
pii: S1465-3249(20)30060-8
doi: 10.1016/j.jcyt.2020.02.005
pii:
doi:
Substances chimiques
Culture Media, Conditioned
0
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
261-275Informations de copyright
Copyright © 2020 International Society for Cell and Gene Therapy. Published by Elsevier Inc. All rights reserved.