Critical issues of clinical human embryonic stem cell therapy for brain repair

被引:147
作者
Li, Jia-Yi [1 ]
Christophersen, Nicolaj S. [1 ]
Hall, Vanessa [1 ]
Soulet, Denis [1 ]
Brundin, Patrik [1 ]
机构
[1] Lund Univ, Dept Expt Med Sci, Neuronal Survival Unit, Wallenberg Neurosci Ctr, S-22184 Lund, Sweden
关键词
D O I
10.1016/j.tins.2007.12.001
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Embryonic stem cells (ESCs) provide hope as a potential regenerative therapy for neurological conditions such as Parkinson's disease and spinal cord injury. Currently, ESC-based nervous system repair faces several problems. One major hurdle is related to problems in generating large and defined populations of the desired types of neurons from human ESCs (hESCs). Moreover, survival of grafted hESC-derived cells has varied and functional recovery in recipient animals has often been disappointing. Importantly, in clinical trials, adverse effects after surgery, including tumors or vigorous immune reactions, must be avoided. Here we highlight attempts to overcome these hurdles with hESCs intended for central nervous system repair. We focus on hESC-derived dopamine-producing neurons that can be grafted in Parkinson's disease and identify critical experiments that need to be conducted before clinical trials can occur.
引用
收藏
页码:146 / 153
页数:8
相关论文
共 68 条
[11]   Karyotypic stability, genotyping, differentiation, feeder-free maintenance, and gene expression sampling in three human embryonic stem cell lines derived prior to August 9, 2001 [J].
Brimble, SN ;
Zeng, XM ;
Weiler, DA ;
Luo, YQ ;
Liu, Y ;
Lyons, IG ;
Freed, WJ ;
Robins, AJ ;
Rao, MS ;
Schulz, TC .
STEM CELLS AND DEVELOPMENT, 2004, 13 (06) :585-597
[12]   Embryonic stem cell-derived glial precursors:: A source of myelinating transplants [J].
Brüstle, O ;
Jones, KN ;
Learish, RD ;
Karram, K ;
Choudhary, K ;
Wiestler, OD ;
Duncan, ID ;
McKay, RDG .
SCIENCE, 1999, 285 (5428) :754-756
[13]   Karyotype of human ES cells during extended culture [J].
Buzzard, JJ ;
Gough, NM ;
Crook, JM ;
Colman, A .
NATURE BIOTECHNOLOGY, 2004, 22 (04) :381-382
[14]   Large stem cell grafts could lead to erroneous interpretations of behavioral results? [J].
Nicolaj Strøyer Christophersen ;
Patrik Brundin .
Nature Medicine, 2007, 13 (2) :118-118
[15]   Genetic selection of sox1GFP-expressing neural precursors removes residual tumorigenic pluripotent stem cells and attenuates tumor formation after transplantation [J].
Chung, S. ;
Shin, B. -S. ;
Hedlund, E. ;
Pruszak, J. ;
Ferree, A. ;
Kang, Un Jung ;
Isacson, Ole ;
Kim, Kwang-Soo .
JOURNAL OF NEUROCHEMISTRY, 2006, 97 (05) :1467-1480
[16]   The homeodomain transcription factor Pitx3 facilitates differentiation of mouse embryonic stem cells into AHD2-expressing dopaminergic neurons [J].
Chung, S ;
Hedlund, E ;
Hwang, M ;
Kim, DW ;
Shin, BS ;
Hwang, DY ;
Kang, UJ ;
Isacson, O ;
Kim, KS .
MOLECULAR AND CELLULAR NEUROSCIENCE, 2005, 28 (02) :241-252
[17]  
CORREIA AS, IN PRESS FRONT NEURO
[18]   Recurrent gain of chromosomes 17q and 12 in cultured human embryonic stem cells [J].
Draper, JS ;
Smith, K ;
Gokhale, P ;
Moore, HD ;
Maltby, E ;
Johnson, J ;
Meisner, L ;
Zwaka, TP ;
Thomson, JA ;
Andrews, PW .
NATURE BIOTECHNOLOGY, 2004, 22 (01) :53-54
[19]   Inflammation is detrimental for neurogenesis in adult brain [J].
Ekdahl, CT ;
Claasen, JH ;
Bonde, S ;
Kokaia, Z ;
Lindvall, O .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (23) :13632-13637
[20]   Host-dependent tumorigenesis of embryonic stem cell transplantation in experimental stroke [J].
Erdö, F ;
Bührle, C ;
Blunk, J ;
Hoehn, M ;
Xia, T ;
Fleischmann, B ;
Föcking, M ;
Küstermann, E ;
Kolossov, E ;
Hescheler, T ;
Hossmann, KA ;
Trapp, T .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2003, 23 (07) :780-785