Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells.

Autor: Hajmousa G; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713, GZ, Groningen, the Netherlands., Przybyt E; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713, GZ, Groningen, the Netherlands., Pfister F; 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Paredes-Juarez GA; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713, GZ, Groningen, the Netherlands., Moganti K; Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Busch S; 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Kuipers J; Department of Cell Biology, Molecular Imaging and Electron Microscopy, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands., Klaassen I; Ocular Angiogenesis Group, Departments of Ophthalmology and Medical Biology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands., van Luyn MJA; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713, GZ, Groningen, the Netherlands., Krenning G; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713, GZ, Groningen, the Netherlands., Hammes HP; 5th Medical Department, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Harmsen MC; Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1 (EA11), 9713, GZ, Groningen, the Netherlands. m.c.harmsen@umcg.nl.
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2018 Nov; Vol. 61 (11), pp. 2371-2385. Date of Electronic Publication: 2018 Aug 27.
DOI: 10.1007/s00125-018-4713-0
Abstrakt: Aims/hypothesis: The immunomodulatory capacity of adipose tissue-derived stromal cells (ASCs) is relevant for next-generation cell therapies that aim to reverse tissue dysfunction such as that caused by diabetes. Pericyte dropout from retinal capillaries underlies diabetic retinopathy and the subsequent aberrant angiogenesis.
Methods: We investigated the pericytic function of ASCs after intravitreal injection of ASCs in mice with retinopathy of prematurity as a model for clinical diabetic retinopathy. In addition, ASCs influence their environment by paracrine signalling. For this, we assessed the immunomodulatory capacity of conditioned medium from cultured ASCs (ASC-Cme) on high glucose (HG)-stimulated bovine retinal endothelial cells (BRECs).
Results: ASCs augmented and stabilised retinal angiogenesis and co-localised with capillaries at a pericyte-specific position. This indicates that cultured ASCs exert juxtacrine signalling in retinal microvessels. ASC-Cme alleviated HG-induced oxidative stress and its subsequent upregulation of downstream targets in an NF-κB dependent fashion in cultured BRECs. Functionally, monocyte adhesion to the monolayers of activated BRECs was also decreased by treatment with ASC-Cme and correlated with a decline in expression of adhesion-related genes such as SELE, ICAM1 and VCAM1.
Conclusions/interpretation: The ability of ASC-Cme to immunomodulate HG-challenged BRECs is related to the length of time for which ASCs were preconditioned in HG medium. Conditioned medium from ASCs that had been chronically exposed to HG medium was able to normalise the HG-challenged BRECs to normal glucose levels. In contrast, conditioned medium from ASCs that had been exposed to HG medium for a shorter time did not have this effect. Our results show that the manner of HG preconditioning of ASCs dictates their immunoregulatory properties and thus the potential outcome of treatment of diabetic retinopathy.
Databáze: MEDLINE
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