Embryonic and adult stem cells as a source for cell therapy in Parkinson's disease

被引:38
作者
Levy, YS
Stroomza, M
Melamed, E
Offen, D
机构
[1] Rabin Med Ctr, Felsenstein Med Res Ctr, Neurosci Lab, Petah Tiqwa, Israel
[2] Rabin Med Ctr, Dept Neurol, Petah Tiqwa, Israel
[3] Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel
关键词
D O I
10.1385/JMN:24:3:353
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The rationale behind the use of cells as therapeutic modalities for neurodegenerative diseases in general, and in Parkinson's disease (PD) in particular, is that they will improve patient's functioning by replacing the damaged cell population. It is reasoned that these cells will survive, grow neurites, establish functional synapses, integrate best and durably with the host tissue mainly in the striatum, renew the impaired wiring, and lead to meaningful clinical improvement. To increase the generation of dopamine, researchers have already transplanted non-neuronal cells, without any genetic manipulation or after introduction of genes such as tyrosine hydroxylase, in animal models of PD. Because these cells were not of neuronal origin, they developed without control, did not integrate well into the brain parenchyma, and their survival rates were low. Clinical experiments using cell transplantation as a therapy for PD have been conducted since the 1980s. Most of these experiments used fetal dopaminergic cells originating in the ventral mesencephalic tissue obtained from fetuses. Although it was shown that the transplanted cells survived and some patients benefited from this treatment, others suffered from severe dyskinesia, probably caused by the graft's excessive and uncontrolled production and release of dopamine. It is now recognized that cell-replacement strategy will be effective in PD only if the transplanted cells have the same abilities, such as dopamine synthesis and control release, reuptake, and metabolizing dopamine, as the original dopaminergic neurons. Recent studies on embryonic and adult stem cells have demonstrated that cells are able to both self-renew and produce differentiated tissues, including dopaminergic neurons. These new methods offer real hope for tissue replacement in a wide range of diseases, especially PD. In this review we summarize the evidence of dopaminergic neuron generation from embryonic and adult stem cells, and discuss their application for cell therapy in PD.
引用
收藏
页码:353 / 385
页数:33
相关论文
共 167 条
[41]   HUMAN EMBRYONIC DOPAMINE NEURONS XENOGRAFTED TO THE RAT - EFFECTS OF CRYOPRESERVATION AND VARYING REGIONAL SOURCE OF DONOR CELLS ON TRANSPLANT SURVIVAL, MORPHOLOGY AND FUNCTION [J].
FRODL, EM ;
DUAN, WM ;
SAUER, H ;
KUPSCH, A ;
BRUNDIN, P .
BRAIN RESEARCH, 1994, 647 (02) :286-298
[42]  
Gage FH, 1998, NATURE, V392, P18
[43]   Neurogenesis in the neocortex of adult primates [J].
Gould, E ;
Reeves, AJ ;
Graziano, MSA ;
Gross, CG .
SCIENCE, 1999, 286 (5439) :548-552
[44]   Differential dissection of the rat E16 ventral mesencephalon and survival and reinnervation of the 6-OHDA-lesioned striatum by a subset of aldehyde dehydrogenase-positive TH neurons [J].
Haque, NSK ;
LeBlanc, CJ ;
Isacson, O .
CELL TRANSPLANTATION, 1997, 6 (03) :239-248
[45]   Plasticity of marrow-derived stem cells [J].
Herzog, EL ;
Chai, L ;
Krause, DS .
BLOOD, 2003, 102 (10) :3483-3493
[46]   Bone marrow as a source of endothelial cells and NeuN-expressing cells after stroke [J].
Hess, DC ;
Hill, WD ;
Martin-Studdard, A ;
Carroll, J ;
Brailer, J ;
Carothers, J .
STROKE, 2002, 33 (05) :1362-1368
[47]   Mechanisms of disease: Nuclear transplantation, embryonic stem cells, and the potential for cell therapy [J].
Hochedlinger, K ;
Jaenisch, R .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 349 (03) :275-286
[48]   News focus - Plasticity: Time for a reappraisal? [J].
Holden, C ;
Vogel, G .
SCIENCE, 2002, 296 (5576) :2126-2129
[49]   Expression of tyrosine hydroxylase in newly differentiated neurons from a human cell line (hNT) [J].
Iacovitti, L ;
Stull, ND .
NEUROREPORT, 1997, 8 (06) :1471-1474
[50]   Differentiation of human dopamine neurons from an embryonic carcinomal stem cell line [J].
Iacovitti, L ;
Stull, ND ;
Jin, H .
BRAIN RESEARCH, 2001, 912 (01) :99-104