Human adipose tissue-derived stromal cells act as functional pericytes in mice and suppress high-glucose-induced proinflammatory activation of bovine retinal endothelial cells
DIABETOLOGIA
Authors: Hajmousa, Ghazaleh; Przybyt, Ewa; Pfister, Frederick; Paredes-Juarez, Genaro A.; Moganti, Kondaiah; Busch, Stephanie; Kuipers, Jeroen; Klaassen, Ingeborg; van Luyn, Marja J. A.; Krenning, Guido; Hammes, Hans-Peter; Harmsen, Martin C.
Abstract
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. 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). 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-kappa B 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. 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.
Comparison of Stemness and Gene Expression between Gingiva and Dental Follicles in Children
STEM CELLS INTERNATIONAL
Authors: Kang, Chung-Min; Kim, Seong-Oh; Jeon, Mijeong; Choi, Hyung-Jun; Jung, Han-Sung; Lee, Jae-Ho
Abstract
The aim of this study was to compare the differential gene expression and stemness in the human gingiva and dental follicles (DFs) according to their biological characteristics. Gingiva (n = 9) and DFs (n = 9) were collected from 18 children. Comparative gene expression profiles were collected using cDNA microarray. The expression of development, chemotaxis, mesenchymal stem cells (MSCs), and induced pluripotent stemcells (iPSs) related genes was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Histological analysis was performed using hematoxylin-eosin and immunohistochemical staining. Gingiva had greater expression of genes related to keratinization, ectodermal development, and chemotaxis whereas DFs exhibited higher expression levels of genes related to tooth and embryo development. qRT-PCR analysis showed that the expression levels of iPSc factors including SOX2, KLF4, and C-MYC were 58.5 +/- 26.3, 12.4 +/- 3.5, and 12.2 +/- 1.9 times higher in gingiva and VCAM1 (CD146) and ALCAM (CD166) were 33.5 +/- 6.9 and 4.3 +/- 0.8 times higher in DFs. Genes related to MSCs markers including CD13, CD34, CD73, CD90, and CD105 were expressed at higher levels in DFs. The results of qRT-PCR and IHC staining supported the microarray analysis results. Interestingly, this study demonstrated transcription factors of iPS cells were expressed at higher levels in the gingiva. Given the minimal surgical discomfort and simple accessibility, gingiva is a good candidate stem cell source in regenerative dentistry.