scholarly journals Exploring the Mesenchymal Stem Cell Secretome for Corneal Endothelial Proliferation

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Bert Van den Bogerd ◽  
Nadia Zakaria ◽  
Steffi Matthyssen ◽  
Carina Koppen ◽  
Sorcha Ní Dhubhghaill

Ex vivo grown human corneal endothelial cells (HCEnC) are a new emerging treatment option to treat visually impaired patients aimed at alleviating the current global donor shortage. Expanding HCEnC is still challenging, and obtaining cells in sufficient quantities is a limiting factor. It is already known that conditioned medium obtained from bone marrow mesenchymal stem cells can stimulate the proliferation of endothelial cells. The aim of this study was to take this work a step further to identify some of the underlying factors responsible. We confirmed the stimulatory effect of the mesenchymal stem cell secretome seen previously and separated the exosomes from the soluble proteins using size exclusion chromatography. We demonstrated the presence of exosomes and soluble proteins in the early and late fractions, respectively, with transmission electron microscopy and protein assays. Proliferation studies demonstrated that growth stimulation could be reproduced with the later protein-rich fractions but not with the exosome-rich fraction. Antibody assays revealed the presence of the secreted proteins EGF, IGFBP2, and IGFBP6 in protein-high fractions, but the growth enhancement was not seen with purified protein formulations. In conclusion, we confirmed the stimulatory effect of stem cell-conditioned medium and have determined that the effect was attributable to the proteins rather than to the exosomes. We were not able to reproduce the growth stimulation, however, with the pure recombinant protein candidates tested. Specific identification of the underlying proteins using proteomics could render a bioactive protein that can be used for ex vivo expansion of cells or as an in vivo drug to treat early corneal endothelial damage.

2021 ◽  
Vol 4 (3) ◽  
pp. 2398-2407
Author(s):  
Lei Xu ◽  
Regine Willumeit-Römer ◽  
Bérengère J. C. Luthringer-Feyerabend

RSC Advances ◽  
2021 ◽  
Vol 11 (30) ◽  
pp. 18685-18692
Author(s):  
Hiroki Masuda ◽  
Yoshinori Arisaka ◽  
Masahiro Hakariya ◽  
Takanori Iwata ◽  
Tetsuya Yoda ◽  
...  

Molecular mobility of polyrotaxane surfaces promoted mineralization in a co-culture system of mesenchymal stem cells and endothelial cells.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.


2021 ◽  
Vol 20 (2) ◽  
pp. 426-430
Author(s):  
Nurhasan Agung Prabowo ◽  
Zainal Arifin Adnan ◽  
Arief Nurudhin ◽  
Yulyani Werdiningsih ◽  
Kukuh Prasetyo

Background: Systemic lupus erythematosus is a chronic autoimmune disease that affects target organs. mesenchymal stem cell conditioned medium has immunosuppressive, anti-inflammatory, and immunoregulatory properties in lupus. Methyl prednisolone is a standard drug for lupus with immunosuppressive and anti-inflammatory properties. This study aims to compare the therapeutic effect of mesenchymal stem cell conditioned medium administration compared to methyl prednisolone on interleukin 10 levels and the degree of pulmonary vasculitis of lupus mice. Methods: The subjects were 24 female mice of Mus musculus Balb/C strain, which were categorized into 4 groups of 8 mice, i.e. the control group receiving 0.5 cc of 0.9% NaCl injection and placebo, the lupus group receiving 0.5 cc of pristane injection and placebo, and the treatment mesenchymal stem cell conditioned medium group receiving 0.5 cc pristane injection and mesenchymal stem cell conditioned medium 0,5 cc, and methylprednisolone group receiving 0,5 cc pristiane injection and methylprednisolone p.o 1,5 mg/kgbodyweight. After 24 days the mice were terminated and kidney and blood samples were taken. Statistical analysis was performed using ANOVA test followed by independent T-test. The p value was considered significant when the p < 0.05. Results: The study showed that there was no difference on the levels of interleukin level10 among mesenchymal stem cell conditioned medium goup and methyl prednisolone group (CM = 5,94 ± 2,49 pg/mL, mp = 5,86+1,73 pg/mL; p = 1) and the degree of pulmonary vasculitis (CM= 1,94 ± 0,25, MP=1,89+ 0,11 pg/ml; p = 0.667). Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice. Conclusion: Mesenchymal stem cell conditioned medium as good as methyl prednisolone in decreasing levels of interleukin 10 and the degree of pulmonary vasculitis in lupus mice Bangladesh Journal of Medical Science Vol.20(2) 2021 p.426-430


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