Cell Therapy for Multiple Sclerosis

被引:32
作者
Ben-Hur, Tamir [1 ]
机构
[1] Hadassah Hebrew Univ Hosp, Agnes Ginges Ctr Human Neurogenet, Dept Neurol, IL-91120 Jerusalem, Israel
关键词
Multiple sclerosis; stem cell; transplantation; remyelination; immunomodulation; NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; OLFACTORY ENSHEATHING CELLS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; OLIGODENDROCYTE PROGENITOR CELLS; SPINAL-CORD-INJURY; MYELINATION FOLLOWING TRANSPLANTATION; FUNCTIONAL DOPAMINERGIC-NEURONS; SUBCORTICAL WHITE-MATTER; AGE-RELATED DECREASE;
D O I
10.1007/s13311-011-0073-x
中图分类号
R74 [神经病学与精神病学];
学科分类号
100204 [神经病学];
摘要
The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.
引用
收藏
页码:625 / 642
页数:18
相关论文
共 298 条
[1]
Human mesenchymal stem cells modulate allogeneic immune cell responses [J].
Aggarwal, S ;
Pittenger, MF .
BLOOD, 2005, 105 (04) :1815-1822
[2]
A functional role for EGFR signaling in myelination and remyelination [J].
Aguirre, Adan ;
Dupree, Jeff L. ;
Mangin, J. M. ;
Gallo, Vittorio .
NATURE NEUROSCIENCE, 2007, 10 (08) :990-1002
[3]
Neuroprotective Effect of Transplanted Human Embryonic Stem Cell-Derived Neural Precursors in an Animal Model of Multiple Sclerosis [J].
Aharonowiz, Michal ;
Einstein, Ofira ;
Fainstein, Nina ;
Lassmann, Hans ;
Reubinoff, Benjamin ;
Ben-Hur, Tamir .
PLOS ONE, 2008, 3 (09)
[4]
AHMED S, 1995, J NEUROSCI, V15, P5765
[5]
Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinal cord [J].
Akiyama, Y ;
Honmou, O ;
Kato, T ;
Uede, T ;
Hashi, K ;
Kocsis, JD .
EXPERIMENTAL NEUROLOGY, 2001, 167 (01) :27-39
[6]
Akiyama Y, 2002, J NEUROSCI, V22, P6623
[7]
POSTNATAL NEUROGENESIS IN GUINEA-PIG [J].
ALTMAN, J ;
DAS, GD .
NATURE, 1967, 214 (5093) :1098-&
[8]
[9]
Fusion of bone-marrow-derived cells with Purkinje neurons, cardiomyocytes and hepatocytes [J].
Alvarez-Dolado, M ;
Pardal, R ;
Garcia-Vardugo, JM ;
Fike, JR ;
Lee, HO ;
Pfeffer, K ;
Lois, C ;
Morrison, SJ ;
Alvarez-Buylla, A .
NATURE, 2003, 425 (6961) :968-973
[10]
Human adult bone marrow-derived somatic cell therapy results in functional recovery and axonal plasticity following stroke in the rat [J].
Andrews, E. M. ;
Tsai, S. -Y. ;
Johnson, S. C. ;
Farrer, J. R. ;
Wagner, J. P. ;
Kopen, G. C. ;
Kartje, G. L. .
EXPERIMENTAL NEUROLOGY, 2008, 211 (02) :588-592