Iris pigment epithelial cells: a possible cell source for the future treatment of neurodegenerative diseases.
For the treatment of neurodegenerative disorders such as Parkinson's disease cell or gene therapeutical options are increasingly verified. For such approaches, neural stem cells or astrocytes are discussed as possible cell candidates. As also fetal retinal pigment epithelial cells have been successfully tested for such therapeutical options, we investigated the potential of iris pigment epithelial cells as an autologous source for future cell replacement therapies. Using the ELISA technique, we looked for the secretion of neurotrophic factors under basal and stimulated conditions by iris pigment epithelial cells (IPE) cells and compared them with the secretion of retinal pigment epithelial cells (RPE) cells. As iron plays a causative role in cell death during Parkinson's disease, the iron-binding capacity by IPE cells was investigated. Furthermore, we checked the integrative capacity of IPE cells after transplantation into the striatum of adult rats. Our data reveal that IPE cells produce and secrete a variety of neurotrophic factors which can be stimulated after treatment with cytokines. Following transplantation, the cells can be easily detected by their pigmentation, survive for at least 8 weeks and as shown by electron microscopy integrate within the host tissue. Moreover, cells can be transduced with high efficiency using a third generation adenoviral vector, making them promising vehicles to locally deliver therapeutic proteins for the treatment of neurodegenerative diseases in a combined cell and gene therapeutical approach.
Arnhold
S
S
Department of Anatomy I, University of Cologne, Cologne, Germany. stefan.arnhold@uni-koeln.de
Semkova
I
I
Andressen
C
C
Lenartz
D
D
Meissner
G
G
Sturm
V
V
Kochanek
S
S
Addicks
K
K
Schraermeyer
U
U
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D002469:Cell Separation; D004847:Epithelial Cells / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007498:Iris / Q000166:cytology*; D007501:Iron / Q000378:metabolism; D017072:Neostriatum / Q000166:cytology / Q000601:surgery; D009414:Nerve Growth Factors / Q000096:biosynthesis / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000628:therapy; D010857:Pigment Epithelium of Eye / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure*; D051381:Rats; D020318:Rats, Long-Evans; D013238:Stereotaxic Techniques
C495039:GDNF protein, human; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D007501:Iron