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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 367-379 |
| Number of pages | 13 |
| Journal | Stem Cells |
| Volume | 34 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 1 2016 |
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Keywords
- Bridge molecules
- Cell therapy
- Phagocytosis
- Receptor tyrosine kinase
- Retinal degeneration
- Retinal pigment epithelium
ASJC Scopus subject areas
- Cell Biology
- Developmental Biology
- Molecular Medicine
Cite this
Human umbilical tissue-derived cells rescue retinal pigment epithelium dysfunction in retinal degeneration. / Cao, Jing; Murat, Christopher; An, Weijun; Yao, Xiang; Lee, John; Santulli-Marotto, Sandra; Harris, Ian R.; Inana, George.
In: Stem Cells, Vol. 34, No. 2, 01.02.2016, p. 367-379.Research output: Contribution to journal › Article
}
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
PY - 2016/2/1
Y1 - 2016/2/1
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.
AB - 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.
KW - Bridge molecules
KW - Cell therapy
KW - Phagocytosis
KW - Receptor tyrosine kinase
KW - Retinal degeneration
KW - Retinal pigment epithelium
UR - http://www.scopus.com/inward/record.url?scp=84958240649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84958240649&partnerID=8YFLogxK
U2 - 10.1002/stem.2239
DO - 10.1002/stem.2239
M3 - Article
C2 - 26523756
AN - SCOPUS:84958240649
VL - 34
SP - 367
EP - 379
JO - Stem Cells
JF - Stem Cells
SN - 1066-5099
IS - 2
ER -