Stromal cells cultivated from the choroid of human eyes display a mesenchymal stromal cell (MSC) phenotype and inhibit the proliferation of choroidal vascular endothelial cells in vitro

被引:6
作者
Alexander, Nadine [1 ,2 ]
Walshe, Jennifer [2 ]
Richardson, Neil A. [1 ,2 ]
Futrega, Kathryn [1 ,3 ]
Doran, Michael R. [1 ,3 ]
Harkin, Damien G. [1 ,2 ]
Shadforth, Audra M. A. [1 ,2 ]
机构
[1] Griffith Univ Nathan, Sch Environm & Sci, Nathan, Qld 4111, Australia
[2] Queensland Eye Inst, 140 Melbourne St, South Brisbane, Qld 4101, Australia
[3] Queensland Univ Technol, Translat Res Inst, Stem Cell Therapies Lab, Brisbane, Qld, Australia
关键词
Choroid; Mesenchymal stromal cell; Choroidal stromal cells; Vascular endothelial cell; Cadaveric eye tissue; GROWTH-FACTOR; STEM-CELLS; RESISTANCE; COLONIES; CULTURES; THERAPY; LIMBUS;
D O I
10.1016/j.exer.2020.108201
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
Mesenchymal stromal cells (MSC), with progenitor cell and immunological properties, have been cultivated from numerous vascularized tissues including bone marrow, adipose tissue and the corneal-limbus of the eye. After observing mesenchymal cells as contaminants in primary cultures of vascular endothelial cells derived from the choroidal tunic of the human eye, we investigated whether the choroid might also provide a source of cultured MSC. Moreover, we examined the effect of the choroidal stromal cells (Ch-SC) on the proliferation of freshly isolated choroidal vascular endothelial cells (ChVEC) in vitro. The phenotype of cultures established from five choroidal tissue donors was examined by flow cytometry and immunocytochemistry. The potential for mesenchymal cell differentiation was examined in parallel with MSC established from human bone marrow. Additional cultures were growth-arrested by treatment with mitomycin-C, before being tested as a potential feeder layer for ChVEC. The five unique cultures established from choroidal stroma displayed a phenotype consistent with the accepted definition for MSC (CD34(-), CD45(-), HLA-DR-, CD73(+), CD90(+), and CD105(+)), including the capacity for mesenchymal differentiation when cultivated under osteogenic, adipogenic and chondrogenic conditions. Growth-arrested Ch-SC inhibited the proliferation of ChVEC derived from five separate donors. Cultures of Ch-SC secreted approximately 40-fold higher concentrations of the anti-angiogenic factor pigment epithelium derived factor (PEDF/serpin F1) compared to the pro-angiogenic factor, vascular endothelial growth factor (VEGF), regardless of normal or growth-arrested state. Our results provide first evidence of a resident MSC cell type within the choroid and encourage investigation of new mechanisms for altering the growth of ChVEC.
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页数:10
相关论文
共 33 条
[1]  
Atkinson K., 2017, The Biology and Therapeutic Application of Mesenchymal Cells
[2]   The dynamic nature of Bruch's membrane [J].
Booij, J. C. ;
Baas, D. C. ;
Beisekeeva, J. ;
Gorgels, T. G. M. F. ;
Bergen, A. A. B. .
PROGRESS IN RETINAL AND EYE RESEARCH, 2010, 29 (01) :1-18
[3]   Mesenchymal Stem Cells in the Human Corneal Limbal Stroma [J].
Branch, Matthew James ;
Hashmani, Khurram ;
Dhillon, Permesh ;
Jones, D. Rhodri E. ;
Dua, Harminder Singh ;
Hopkinson, Andrew .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2012, 53 (09) :5109-5116
[4]   Immunosuppressive properties of mesenchymal stromal cell cultures derived from the limbus of human and rabbit corneas [J].
Bray, Laura J. ;
Heazlewood, Celena F. ;
Munster, David J. ;
Hutmacher, Dietmar W. ;
Atkinson, Kerry ;
Harkin, Damien G. .
CYTOTHERAPY, 2014, 16 (01) :64-73
[5]   Isolation, culture, and characterisation of human macular inner choroidal microvascular endothelial cells [J].
Browning, AC ;
Gray, T ;
Amoaku, WM .
BRITISH JOURNAL OF OPHTHALMOLOGY, 2005, 89 (10) :1343-1347
[6]   Structural and molecular changes in the aging choroid: implications for age-related macular degeneration [J].
Chirco, K. R. ;
Sohn, E. H. ;
Stone, E. M. ;
Tucker, B. A. ;
Mullins, R. F. .
EYE, 2017, 31 (01) :10-25
[7]   Mesenchymal stem cells reside in virtually all post-natal organs and tissues [J].
da Silva Meirelles, Lindolfo ;
Chagastelles, Pedro Cesar ;
Nardi, Nance Beyer .
JOURNAL OF CELL SCIENCE, 2006, 119 (11) :2204-2213
[8]   Characterization of a tissue-engineered choroid [J].
Djigo, Aicha Dede ;
Berube, Julie ;
Landreville, Solange ;
Proulx, Stephanie .
ACTA BIOMATERIALIA, 2019, 84 :305-316
[9]   Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement [J].
Dominici, M. ;
Le Blanc, K. ;
Mueller, I. ;
Slaper-Cortenbach, I. ;
Marini, F. C. ;
Krause, D. S. ;
Deans, R. J. ;
Keating, A. ;
Prockop, D. J. ;
Horwitz, E. M. .
CYTOTHERAPY, 2006, 8 (04) :315-317
[10]   DEVELOPMENT OF FIBROBLAST COLONIES IN MONOLAYER CULTURES OF GUINEA-PIG BONE MARROW AND SPLEEN CELLS [J].
FRIEDENSTEIN, AJ ;
CHAILAKHJAN, RK ;
LALYKINA, KS .
CELL AND TISSUE KINETICS, 1970, 3 (04) :393-+