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Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats.
Invest Ophthalmol Vis Sci. 2006 Sep; 47(9):4121-9.IO

Abstract

PURPOSE

To determine the potential of adenovirally transduced bone marrow stromal cells (BMSCs) to differentiate into retinal pigment epithelial-like cells and to evaluabe possible rescue effects after transplantation into the retinas of Royal College of Surgeons (RCS) rats.

METHODS

Through a high-capacity adenoviral vector expressing either green fluorescent protein (GFP) or pigment epithelial-derived factor (PEDF), rat MSCs were transduced in vitro before subretinal transplantation into Wistar rats or, alternatively, RCS rats. Two months after cell injection, the rats were killed and the eyes enucleated. The eyes were then investigated light microscopically or processed for electron microscopic investigations. Cell differentiation and integration were analyzed immunocytochemically using antibodies against cytokeratin and the tight junction protein ZO-1. Electroretinography was performed 16 days after injection of cells, to check whether a functional rescue could be detected.

RESULTS

In vitro experiments in cocultured human MSCs and human RPE cells showed that MSCs adopted RPE-like characteristics. In grafting experiments, some rat MSCs integrate into the host RPE cell layer of Wistar and RCS rats, indicated by their hexagonal morphology. Subretinally transplanted cells express the epithelial marker cytokeratin and establish tight junctions with the host RPE cells. Furthermore, rescue effects can be demonstrated after grafting of vector-transduced and nontransduced MSCs in semithin sections of dystrophic retinas. Ultrastructurally, MSCs can be detected on top of host RPE and in close contact with photoreceptor outer segments phagocytosing rod outer segments.

CONCLUSIONS

Taken together, these results raise the possibility that MSCs have the potency to replace diseased RPE cells and deliver therapeutic proteins into the subretinal space to protect photoreceptor cells from degeneration.

Authors+Show Affiliations

Department of Anatomy I, University of Cologne, Cologne, Germany. stefan.arnhold@uni-koeln.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16936132

Citation

Arnhold, Stefan, et al. "Adenovirally Transduced Bone Marrow Stromal Cells Differentiate Into Pigment Epithelial Cells and Induce Rescue Effects in RCS Rats." Investigative Ophthalmology & Visual Science, vol. 47, no. 9, 2006, pp. 4121-9.
Arnhold S, Heiduschka P, Klein H, et al. Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats. Invest Ophthalmol Vis Sci. 2006;47(9):4121-9.
Arnhold, S., Heiduschka, P., Klein, H., Absenger, Y., Basnaoglu, S., Kreppel, F., Henke-Fahle, S., Kochanek, S., Bartz-Schmidt, K. U., Addicks, K., & Schraermeyer, U. (2006). Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats. Investigative Ophthalmology & Visual Science, 47(9), 4121-9.
Arnhold S, et al. Adenovirally Transduced Bone Marrow Stromal Cells Differentiate Into Pigment Epithelial Cells and Induce Rescue Effects in RCS Rats. Invest Ophthalmol Vis Sci. 2006;47(9):4121-9. PubMed PMID: 16936132.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adenovirally transduced bone marrow stromal cells differentiate into pigment epithelial cells and induce rescue effects in RCS rats. AU - Arnhold,Stefan, AU - Heiduschka,Peter, AU - Klein,Helmut, AU - Absenger,Yvonne, AU - Basnaoglu,Serkan, AU - Kreppel,Florian, AU - Henke-Fahle,Sylvia, AU - Kochanek,Stefan, AU - Bartz-Schmidt,Karl-Ulrich, AU - Addicks,Klaus, AU - Schraermeyer,Ulrich, PY - 2006/8/29/pubmed PY - 2006/10/3/medline PY - 2006/8/29/entrez SP - 4121 EP - 9 JF - Investigative ophthalmology & visual science JO - Invest Ophthalmol Vis Sci VL - 47 IS - 9 N2 - PURPOSE: To determine the potential of adenovirally transduced bone marrow stromal cells (BMSCs) to differentiate into retinal pigment epithelial-like cells and to evaluabe possible rescue effects after transplantation into the retinas of Royal College of Surgeons (RCS) rats. METHODS: Through a high-capacity adenoviral vector expressing either green fluorescent protein (GFP) or pigment epithelial-derived factor (PEDF), rat MSCs were transduced in vitro before subretinal transplantation into Wistar rats or, alternatively, RCS rats. Two months after cell injection, the rats were killed and the eyes enucleated. The eyes were then investigated light microscopically or processed for electron microscopic investigations. Cell differentiation and integration were analyzed immunocytochemically using antibodies against cytokeratin and the tight junction protein ZO-1. Electroretinography was performed 16 days after injection of cells, to check whether a functional rescue could be detected. RESULTS: In vitro experiments in cocultured human MSCs and human RPE cells showed that MSCs adopted RPE-like characteristics. In grafting experiments, some rat MSCs integrate into the host RPE cell layer of Wistar and RCS rats, indicated by their hexagonal morphology. Subretinally transplanted cells express the epithelial marker cytokeratin and establish tight junctions with the host RPE cells. Furthermore, rescue effects can be demonstrated after grafting of vector-transduced and nontransduced MSCs in semithin sections of dystrophic retinas. Ultrastructurally, MSCs can be detected on top of host RPE and in close contact with photoreceptor outer segments phagocytosing rod outer segments. CONCLUSIONS: Taken together, these results raise the possibility that MSCs have the potency to replace diseased RPE cells and deliver therapeutic proteins into the subretinal space to protect photoreceptor cells from degeneration. SN - 0146-0404 UR - https://www.unboundmedicine.com/medline/citation/16936132/Adenovirally_transduced_bone_marrow_stromal_cells_differentiate_into_pigment_epithelial_cells_and_induce_rescue_effects_in_RCS_rats_ L2 - https://iovs.arvojournals.org/article.aspx?doi=10.1167/iovs.04-1501 DB - PRIME DP - Unbound Medicine ER -