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J. Clin. Med. 2019, 8(4), 510; https://doi.org/10.3390/jcm8040510

Intra-Vitreal Administration of Microvesicles Derived from Human Adipose-Derived Multipotent Stromal Cells Improves Retinal Functionality in Dogs with Retinal Degeneration

1
Trzebnicka Veterinary Clinic, Department of Ophthalmology, Kosciuszki 18 St, 55-100 Trzebnica, Poland
2
Viva Veterinary Clinic, Department of Ophthalmology, Strachocinska 143 St., 51-518 Wroclaw, Poland
3
Department of Experimental Biology, The Faculty of Biology and Animal Science, University of Environmental and Life Sciences, 50-375 Wroclaw, Poland
4
International Institute of Translational Medicine, Jesionowa 11 St, 55-124 Malin, Poland
5
Royal Veterinary College, London NW1 0TU, UK
6
Ophthalmology Referrals, 25, Great North Road, Brookmans Park, Herts., North Mymms, Hatfield AL9 6LB, UK
7
Faculty of Veterinary Medicine, Equine Clinic-Equine Surgery, Justus-Liebig-University, 35392 Gießen, Germany
*
Author to whom correspondence should be addressed.
Received: 14 March 2019 / Revised: 8 April 2019 / Accepted: 10 April 2019 / Published: 13 April 2019
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Abstract

This study was designed to determine the influence of microvesicles (MVs) derived from multipotent stromal cells isolated from human adipose tissue (hASCs) on retinal functionality in dogs with various types of retinal degeneration. The biological properties of hASC-MVs were first determined using an in vitro model of retinal Muller-like cells (CaMLCs). The in vitro assays included analysis of hASC-MVs influence on cell viability and metabolism. Brain-derived neurotrophic factor (BDNF) expression was also determined. Evaluation of the hASC-MVs was performed under normal and oxidative stress conditions. Preliminary clinical studies were performed on ten dogs with retinal degeneration. The clinical studies included behavioral tests, fundoscopy and electroretinography before and after hASC-MVs intra-vitreal injection. The in vitro study showed that CaMLCs treated with hASC-MVs were characterized by improved viability and mitochondrial potential, both under normal and oxidative stress conditions. Additionally, hASC-MVs under oxidative stress conditions reduced the number of senescence-associated markers, correlating with the increased expression of BDNF. The preliminary clinical study showed that the intra-vitreal administration of hASC-MVs significantly improved the dogs’ general behavior and tracking ability. Furthermore, fundoscopy demonstrated that the retinal blood vessels appeared to be less attenuated, and electroretinography using HMsERG demonstrated an increase in a- and b-wave amplitude after treatment. These results shed promising light on the application of cell-free therapies in veterinary medicine for retinal degenerative disorders treatment. View Full-Text
Keywords: microvesicles; human multipotent stromal cells; retinal regeneration microvesicles; human multipotent stromal cells; retinal regeneration
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Cislo-Pakuluk, A.; Smieszek, A.; Kucharczyk, N.; Bedford, P.G.; Marycz, K. Intra-Vitreal Administration of Microvesicles Derived from Human Adipose-Derived Multipotent Stromal Cells Improves Retinal Functionality in Dogs with Retinal Degeneration. J. Clin. Med. 2019, 8, 510.

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