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Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology 1/2018

22.11.2017 | Basic Science

Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits

verfasst von: Sonia Labrador Velandia, Salvatore Di Lauro, Maria Luz Alonso-Alonso, Soraya Tabera Bartolomé, Girish Kumar Srivastava, José Carlos Pastor, Ivan Fernandez-Bueno

Erschienen in: Graefe's Archive for Clinical and Experimental Ophthalmology | Ausgabe 1/2018

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Abstract

Purpose

To evaluate the feasibility, safety, and biocompatibility of intravitreal injection of human mesenchymal stem cells (MSCs) in immunocompetent pigmented rabbits.

Materials and methods

Thirty-two pigmented rabbits (24 females, 8 males; Chinchilla-New Zealand White) were divided into 8 groups of 4 animals. Commercially prepared human MSCs were injected (0.05 ml) into the post-lens vitreous of the right eyes. Groups 1 and 4 received isotonic medium (Ringer lactate-based), groups 2, 5, 7, and 8 received a low dose of 15 × 106 cells/ml. Groups 3 and 6 received a high dose of 30 × 106 cells/ml. Clinical signs were evaluated and scored before MSCs injection and weekly for 2 or 6 weeks. Animals were sacrificed at 2 or 6 weeks after injection. Eyes, liver, spleen, and gonads were assessed by histology and by fluorescent in situ hybridization to evaluate survival and extraocular migration of MSCs.

Results

There were no relevant clinical findings between control and MSC-injected rabbit eyes at any time point. There were also no relevant histological findings between control and MSC-injected rabbits related to ocular, liver, spleen, or gonad tissues modifications. MSCs survived intravitreally for at least 2 weeks after injection. Extraocular migration of MSCs was not detected.

Conclusions

MSCs are safe and well-tolerated when administered intravitreally at a dose of 15 × 106 cells/ml in pigmented rabbits. These findings enable future research to explore the intravitreal use of commercially prepared allogenic human MSCs in clinical trials of retinal diseases.
Literatur
4.
Zurück zum Zitat Kupersmith MJ, Frohman L, Sanderson M, Jacobs J, Hirschfeld J, Ku C, Warren FA (1997) Aspirin reduces the incidence of second eye NAION: a retrospective study. J Neuroophthalmol 17:250–253CrossRefPubMed Kupersmith MJ, Frohman L, Sanderson M, Jacobs J, Hirschfeld J, Ku C, Warren FA (1997) Aspirin reduces the incidence of second eye NAION: a retrospective study. J Neuroophthalmol 17:250–253CrossRefPubMed
5.
Zurück zum Zitat Beck RW, Hayreh SS, Podhajsky PA, Tan ES, Moke PS (1997) Aspirin therapy in nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 123:212–217CrossRefPubMed Beck RW, Hayreh SS, Podhajsky PA, Tan ES, Moke PS (1997) Aspirin therapy in nonarteritic anterior ischemic optic neuropathy. Am J Ophthalmol 123:212–217CrossRefPubMed
6.
Zurück zum Zitat Group IONDTR (2000) Ischemic optic neuropathy decompression trial: twenty-four-month update. Arch Ophthalmol 118:793–798CrossRef Group IONDTR (2000) Ischemic optic neuropathy decompression trial: twenty-four-month update. Arch Ophthalmol 118:793–798CrossRef
8.
Zurück zum Zitat Beck RW (2000) Does Levodopa improve visual function in NAION? Ophthalmology 107: 1431-1434; discusson 1435-1438 Beck RW (2000) Does Levodopa improve visual function in NAION? Ophthalmology 107: 1431-1434; discusson 1435-1438
9.
Zurück zum Zitat Bernstein SL, Mehrabyan Z, Guo Y, Moianie N (2007) Estrogen is not neuroprotective in a rodent model of optic nerve stroke. Mol Vis 13:1920–1925PubMedPubMedCentral Bernstein SL, Mehrabyan Z, Guo Y, Moianie N (2007) Estrogen is not neuroprotective in a rodent model of optic nerve stroke. Mol Vis 13:1920–1925PubMedPubMedCentral
11.
Zurück zum Zitat Wilhelm B, Ludtke H, Wilhelm H, Group BS (2006) Efficacy and tolerability of 0.2% brimonidine tartrate for the treatment of acute non-arteritic anterior ischemic optic neuropathy (NAION): a 3-month, double-masked, randomised, placebo-controlled trial. Graefes Arch Clin Exp Ophthalmol 244:551–558. https://doi.org/10.1007/s00417-005-0102-8 CrossRef Wilhelm B, Ludtke H, Wilhelm H, Group BS (2006) Efficacy and tolerability of 0.2% brimonidine tartrate for the treatment of acute non-arteritic anterior ischemic optic neuropathy (NAION): a 3-month, double-masked, randomised, placebo-controlled trial. Graefes Arch Clin Exp Ophthalmol 244:551–558. https://​doi.​org/​10.​1007/​s00417-005-0102-8 CrossRef
15.
Zurück zum Zitat Phinney DG, Isakova I (2005) Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 11:1255–1265CrossRefPubMed Phinney DG, Isakova I (2005) Plasticity and therapeutic potential of mesenchymal stem cells in the nervous system. Curr Pharm Des 11:1255–1265CrossRefPubMed
26.
Zurück zum Zitat Levkovitch-Verbin H, Sadan O, Vander S, Rosner M, Barhum Y, Melamed E, Offen D, Melamed S (2010) Intravitreal injections of neurotrophic factors secreting mesenchymal stem cells are neuroprotective in rat eyes following optic nerve transection. Invest Ophthalmol Vis Sci 51:6394–6400. https://doi.org/10.1167/iovs.09-4310 CrossRefPubMed Levkovitch-Verbin H, Sadan O, Vander S, Rosner M, Barhum Y, Melamed E, Offen D, Melamed S (2010) Intravitreal injections of neurotrophic factors secreting mesenchymal stem cells are neuroprotective in rat eyes following optic nerve transection. Invest Ophthalmol Vis Sci 51:6394–6400. https://​doi.​org/​10.​1167/​iovs.​09-4310 CrossRefPubMed
27.
Zurück zum Zitat Kaplan HJ, Chiang CW, Chen J, Song SK (2010) Vitreous volume of the mouse measured by quantitative high-resolution MRI. Invest Ophthalmol Vis Sci 51:4414–4414 Kaplan HJ, Chiang CW, Chen J, Song SK (2010) Vitreous volume of the mouse measured by quantitative high-resolution MRI. Invest Ophthalmol Vis Sci 51:4414–4414
28.
Zurück zum Zitat Hackett R (1991) Eye irritation. In: Marzulli F, Maibach H (eds) Advances in modern toxicology: Dermatoxicology. Hemisphere Publishing Corporation, Washington, DC, pp 749–815 Hackett R (1991) Eye irritation. In: Marzulli F, Maibach H (eds) Advances in modern toxicology: Dermatoxicology. Hemisphere Publishing Corporation, Washington, DC, pp 749–815
33.
Zurück zum Zitat Griffin G, Clark JM, Zurlo J, Ritskes-Hoitinga M (2014) Scientific uses of animals: harm-benefit analysis and complementary approaches to implementing the three Rs. Rev Sci Tech 33:265–272CrossRefPubMed Griffin G, Clark JM, Zurlo J, Ritskes-Hoitinga M (2014) Scientific uses of animals: harm-benefit analysis and complementary approaches to implementing the three Rs. Rev Sci Tech 33:265–272CrossRefPubMed
38.
Zurück zum Zitat Nishihara H (1989) Studies on the ultrastructure of the inner limiting membrane of the retina. I. Surface replication study on the inner limiting membrane of the retina. Nippon Ganka Gakkai Zasshi 93:429–438PubMed Nishihara H (1989) Studies on the ultrastructure of the inner limiting membrane of the retina. I. Surface replication study on the inner limiting membrane of the retina. Nippon Ganka Gakkai Zasshi 93:429–438PubMed
Metadaten
Titel
Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits
verfasst von
Sonia Labrador Velandia
Salvatore Di Lauro
Maria Luz Alonso-Alonso
Soraya Tabera Bartolomé
Girish Kumar Srivastava
José Carlos Pastor
Ivan Fernandez-Bueno
Publikationsdatum
22.11.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Graefe's Archive for Clinical and Experimental Ophthalmology / Ausgabe 1/2018
Print ISSN: 0721-832X
Elektronische ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-017-3842-3

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