title: Signal Factors Secreted by 2D and Spheroid Mesenchymal Stem Cells and by Cocultures of Mesenchymal Stem Cells Derived Microvesicles and Retinal Photoreceptor Neurons.
abstract: We aim to identify levels of signal factors secreted by MSCs cultured in 2D monolayers (2D-MSCs), spheroids (spheroids MSCs), and cocultures of microvesicles (MVs) derived from 2D-MSCs or spheroid MSCs and retinal photoreceptor neurons. We seeded 2D-MSCs, spheroid MSCs, and cells derived from spheroids MSCs at equal numbers. MVs isolated from all 3 culture conditions were incubated with 661W cells. Levels of 51 signal factors in conditioned medium from those cultured conditions were quantified with bead-based assay. We found that IL-8, IL-6, and GROαwere the top three most abundant signal factors. Moreover, compared to 2D-MSCs, levels of 11 cytokines and IL-2Rαwere significantly increased in conditioned medium from spheroid MSCs. Finally, to test if enhanced expression of these factors reflects altered immunomodulating activities, we assessed the effect of 2D-MSC-MVs and 3D-MSC-MVs on CD14+ cell chemoattraction. Compared to 2D-MSC-MVs, 3D-MSC-MVs significantly decreased the chemotactic index of CD14+ cells. Our results suggest that spheroid culture conditions improve the ability of MSCs to selectively secrete signal factors. Moreover, 3D-MSC-MVs also possessed an enhanced capability to promote signal factors secretion compared to 2D-MSC-MVs and may possess enhanced immunomodulating activities and might be a better regenerative therapy for retinal degenerative diseases.
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Hunan Province, China.
authors.forename: Lili
authors.identifier: 0000-0002-8523-3158
authors.initials: L
authors.lastname: Xie
authors.affiliation: Departments of Ophthalmology and Anatomy, Institute for Human Genetics, UCSF School of Medicine, San Francisco, CA, USA.
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Hunan Province, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Hunan Province, China.
authors.forename: Lusi
authors.identifier: 0000-0001-6659-7944
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology, The Second Xiangya Hospital, Central South University, Hunan Province, China.
authors.forename: Bing
authors.identifier: 0000-0001-6594-4019
authors.initials: B
authors.lastname: Jiang