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Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration.
Stem Cells. 2016 Feb; 34(2):367-79.SC

Abstract

Retinal pigment epithelium (RPE) cells perform many functions crucial for retinal preservation and vision. RPE cell dysfunction results in various retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD). Currently, there are no effective treatments for retinal degeneration except for a small percentage of individuals with exudative AMD. Cell therapies targeting RPE cells are being developed in the clinic for the treatment of retinal degeneration. Subretinal injection of human umbilical tissue-derived cells (hUTC) in the Royal College of Surgeons (RCS) rat model of retinal degeneration was shown to preserve photoreceptors and visual function. However, the precise mechanism remains unclear. Here, we demonstrate that hUTC rescue phagocytic dysfunction in RCS RPE cells in vitro. hUTC secrete receptor tyrosine kinase (RTK) ligands brain-derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and glial cell-derived neurotrophic factor (GDNF), as well as opsonizing bridge molecules milk-fat-globule-epidermal growth factor 8 (MFG-E8), growth arrest-specific 6 (Gas6), thrombospondin (TSP)-1, and TSP-2. The effect of hUTC on phagocytosis rescue in vitro is mimicked by recombinant human proteins of these factors and is abolished by siRNA-targeted gene silencing in hUTC. The bridge molecules secreted from hUTC bind to the photoreceptor outer segments and facilitate their ingestion by the RPE. This study elucidates novel cellular mechanisms for the repair of RPE function in retinal degeneration through RTK ligands and bridge molecules, and demonstrates the potential of using hUTC for the treatment of retinal degenerative diseases.

Authors+Show Affiliations

Janssen Research and Development, LLC, Spring House, Pennsylvania, USA.Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.Janssen Research and Development, LLC, San Diego, California, USA.Janssen Research and Development, LLC, Spring House, Pennsylvania, USA.Janssen Research and Development, LLC, Spring House, Pennsylvania, USA.Janssen Research and Development, LLC, Spring House, Pennsylvania, USA.Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26523756

Citation

Cao, Jing, et al. "Human Umbilical Tissue-derived Cells Rescue Retinal Pigment Epithelium Dysfunction in Retinal Degeneration." Stem Cells (Dayton, Ohio), vol. 34, no. 2, 2016, pp. 367-79.
Cao J, Murat C, An W, et al. Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration. Stem Cells. 2016;34(2):367-79.
Cao, J., Murat, C., An, W., Yao, X., Lee, J., Santulli-Marotto, S., Harris, I. R., & Inana, G. (2016). Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration. Stem Cells (Dayton, Ohio), 34(2), 367-79. https://doi.org/10.1002/stem.2239
Cao J, et al. Human Umbilical Tissue-derived Cells Rescue Retinal Pigment Epithelium Dysfunction in Retinal Degeneration. Stem Cells. 2016;34(2):367-79. PubMed PMID: 26523756.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration. AU - Cao,Jing, AU - Murat,Christopher, AU - An,Weijun, AU - Yao,Xiang, AU - Lee,John, AU - Santulli-Marotto,Sandra, AU - Harris,Ian R, AU - Inana,George, Y1 - 2015/11/26/ PY - 2015/07/29/received PY - 2015/09/29/accepted PY - 2015/11/3/entrez PY - 2015/11/3/pubmed PY - 2016/11/1/medline KW - Bridge molecules KW - Cell therapy KW - Phagocytosis KW - Receptor tyrosine kinase KW - Retinal degeneration KW - Retinal pigment epithelium SP - 367 EP - 79 JF - Stem cells (Dayton, Ohio) JO - Stem Cells VL - 34 IS - 2 N2 - Retinal pigment epithelium (RPE) cells perform many functions crucial for retinal preservation and vision. RPE cell dysfunction results in various retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration (AMD). Currently, there are no effective treatments for retinal degeneration except for a small percentage of individuals with exudative AMD. Cell therapies targeting RPE cells are being developed in the clinic for the treatment of retinal degeneration. Subretinal injection of human umbilical tissue-derived cells (hUTC) in the Royal College of Surgeons (RCS) rat model of retinal degeneration was shown to preserve photoreceptors and visual function. However, the precise mechanism remains unclear. Here, we demonstrate that hUTC rescue phagocytic dysfunction in RCS RPE cells in vitro. hUTC secrete receptor tyrosine kinase (RTK) ligands brain-derived neurotrophic factor (BDNF), hepatocyte growth factor (HGF), and glial cell-derived neurotrophic factor (GDNF), as well as opsonizing bridge molecules milk-fat-globule-epidermal growth factor 8 (MFG-E8), growth arrest-specific 6 (Gas6), thrombospondin (TSP)-1, and TSP-2. The effect of hUTC on phagocytosis rescue in vitro is mimicked by recombinant human proteins of these factors and is abolished by siRNA-targeted gene silencing in hUTC. The bridge molecules secreted from hUTC bind to the photoreceptor outer segments and facilitate their ingestion by the RPE. This study elucidates novel cellular mechanisms for the repair of RPE function in retinal degeneration through RTK ligands and bridge molecules, and demonstrates the potential of using hUTC for the treatment of retinal degenerative diseases. SN - 1549-4918 UR - https://www.unboundmedicine.com/medline/citation/26523756/Human_umbilical_tissue_derived_cells_rescue_retinal_pigment_epithelium_dysfunction_in_retinal_degeneration_ L2 - https://doi.org/10.1002/stem.2239 DB - PRIME DP - Unbound Medicine ER -