Iris pigment epithelial cells: a possible cell source for the future treatment of neurodegenerative diseases

被引:18
作者
Arnhold, S
Semkova, I
Andressen, C
Lenartz, D
Meissner, G
Sturm, V
Kochanek, S
Addicks, K
Schraermeyer, U
机构
[1] Univ Cologne, Dept Anat 1, D-50931 Cologne, Germany
[2] Univ Ulm, Sect Genetherapy, Ulm, Germany
[3] Univ Rostock, Inst Anat, Rostock, Germany
[4] Univ Cologne, Clin Stereotaxy & Funct Neurosurg, Cologne, Germany
[5] Univ Tubingen, Sect Expt Vitroretinal Surg, Tubingen, Germany
关键词
pigment epithelial cells; neurotrophic factors; adenoviral vector; ex vivo gene therapy; cell integration;
D O I
10.1016/j.expneurol.2004.02.015
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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 WE 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. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:410 / 417
页数:8
相关论文
共 28 条
[1]  
Andersen J K, 2001, Novartis Found Symp, V235, P11
[2]  
Angelov DN, 1998, GLIA, V24, P155
[3]   IL-1β, IL-2, IL-6 and TNF-α production by peripheral blood mononuclear cells from patients with Parkinson's disease [J].
Bessler, H ;
Djaldetti, R ;
Salman, H ;
Bergman, M ;
Djaldetti, M .
BIOMEDICINE & PHARMACOTHERAPY, 1999, 53 (03) :141-145
[4]   Gene therapeutic strategies for neuroprotection: Implications for Parkinson's disease [J].
Bowers, WJ ;
Howard, DF ;
Federoff, HJ .
EXPERIMENTAL NEUROLOGY, 1997, 144 (01) :58-68
[5]   INTRACEREBRAL GRAFTING OF DOPAMINE NEURONS - EXPERIMENTAL BASIS FOR CLINICAL-TRIALS IN PATIENTS WITH PARKINSONS-DISEASE [J].
BRUNDIN, P ;
STRECKER, RE ;
LINDVALL, O ;
ISACSON, O ;
NILSSON, OG ;
BARBIN, G ;
PROCHIANTZ, A ;
FORNI, C ;
NIEOULLON, A ;
WIDNER, H ;
GAGE, FH ;
BJORKLUND, A .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1987, 495 :476-496
[6]   NEURAL MECHANISMS IN DISORDERS OF MOVEMENT [J].
CROSSMAN, AR .
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY A-PHYSIOLOGY, 1989, 93 (01) :141-149
[7]  
DEXTER DT, 1987, LANCET, V2, P1219
[8]   NEUROTROPHIN-4/5 IS A SURVIVAL FACTOR FOR EMBRYONIC MIDBRAIN DOPAMINERGIC-NEURONS IN ENRICHED CULTURES [J].
HYNES, MA ;
POULSEN, K ;
ARMANINI, M ;
BERKEMEIER, L ;
PHILLIPS, H ;
ROSENTHAL, A .
JOURNAL OF NEUROSCIENCE RESEARCH, 1994, 37 (01) :144-154
[9]   TRANSPLANTED XENOGENEIC NEURAL CELLS IN NEURODEGENERATIVE DISEASE-MODELS EXHIBIT REMARKABLE AXONAL TARGET SPECIFICITY AND DISTINCT GROWTH-PATTERNS OF GLIAL AND AXONAL FIBERS [J].
ISACSON, O ;
DEACON, TW ;
PAKZABAN, P ;
GALPERN, WR ;
DINSMORE, J ;
BURNS, LH .
NATURE MEDICINE, 1995, 1 (11) :1189-1194
[10]   Expression of neurotrophic factors in cultured human retinal pigment epithelial cells [J].
Ishida, K ;
Yoshimura, N ;
Yoshida, M ;
Honda, Y ;
Murase, K ;
Hayashi, K .
CURRENT EYE RESEARCH, 1997, 16 (02) :96-101