Successful Subretinal Delivery and Monitoring of MicroBeads in Mice

被引：19

作者：

Fischer, M. Dominik ^{[1
,2
]}

Goldmann, Tobias ^{[3
]}

Wallrapp, Christine ^{[4
]}

Muehlfriedel, Regine ^{[5
,6
]}

Beck, Susanne C. ^{[5
,6
]}

Stern-Schneider, Gabi ^{[3
]}

Ueffing, Marius ^{[6
]}

Wolfrum, Uwe ^{[3
]}

Seeliger, Mathias W. ^{[5
,6
]}

机构：

[1] Univ Tubingen, Univ Eye Hosp, Ctr Ophthalmol, Tubingen, Germany

[2] Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England

[3] Johannes Gutenberg Univ Mainz, Inst Zool, Dept Cell & Matrix Biol, Mainz, Germany

[4] CellMed AG, Alzenau, Germany

[5] Univ Tubingen, Div Ocular Neurodegenerat, Tubingen, Germany

[6] Univ Tubingen, Inst Ophthalm Res, Ctr Ophthalmol, Tubingen, Germany

来源：

PLOS ONE | 2013年 / 8卷 / 01期

关键词：

CILIARY NEUROTROPHIC FACTOR; GLUCAGON-LIKE PEPTIDE-1; OPTICAL COHERENCE TOMOGRAPHY; MESENCHYMAL STEM-CELLS; MAMMALIAN PHOTORECEPTOR CELLS; SCANNING LASER OPHTHALMOSCOPY; LEBERS CONGENITAL AMAUROSIS; RETINAL DEGENERATION; RETINITIS-PIGMENTOSA; ANIMAL-MODELS;

D O I：

10.1371/journal.pone.0055173

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Background: To monitor viability of implanted genetically engineered and microencapsulated human stem cells (MicroBeads) in the mouse eye, and to study the impact of the beads and/or xenogenic cells on retinal integrity. Methodology/Principal Findings: MicroBeads were implanted into the subretinal space of SV126 wild type mice using an ab externo approach. Viability of microencapsulated cells was monitored by noninvasive retinal imaging (Spectralis (TM) HRA+OCT). Retinal integrity was also assessed with retinal imaging and upon the end of the study by light and electron microscopy. The implanted GFP-marked cells encapsulated in subretinal MicroBeads remained viable over a period of up to 4 months. Retinal integrity and viability appeared unaltered apart from the focal damage due to the surgical implantation, GFAP upregulation, and opsin mistargeting in the immediate surrounding tissue. Conclusions/Significance: The accessibility for routine surgery and its immune privileged state make the eye an ideal target for release system implants for therapeutic substances, including neurotrophic and anti-angiogenic compounds or protein based biosimilars. Microencapsulated human stem cells (MicroBeads) promise to overcome limitations inherent with single factor release systems, as they are able to produce physiologic combinations of bioactive compounds.

引用

页数：8

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