Systemic transplantation of c-kit+ cells exerts a therapeutic effect in a model of amyotrophic lateral sclerosis

被引：48

作者：

Corti, Stefania ^{[1
,2
]}

Nizzardo, Monica ^{[1
]}

Nardini, Martina ^{[1
]}

Donadoni, Chiara ^{[1
]}

Salani, Sabrina ^{[1
]}

Simone, Chiara ^{[1
]}

Falcone, Marianna ^{[1
]}

Riboldi, Giulietta ^{[1
]}

Govoni, Alessandra ^{[1
]}

Bresolin, Nereo ^{[1
,2
,3
]}

Comi, Giacomo P. ^{[1
,2
]}

机构：

[1] Univ Milan, IRCCS Fdn Ca Granda Policlin, Dept Neurol Sci, Dino Ferrari Ctr, I-20122 Milan, Italy

[2] Univ Milan, Ctr Excellence Neurodegenerat Dis, I-20122 Milan, Italy

[3] IRCCS Eugenio Medea, Bosisio Parini, Lecco, Italy

来源：

HUMAN MOLECULAR GENETICS | 2010年 / 19卷 / 19期

关键词：

MOTOR-NEURON DEGENERATION; SPINAL MUSCULAR-ATROPHY; GLUTAMATE TRANSPORTERS; SUPEROXIDE-DISMUTASE; BONE-MARROW; STEM-CELLS; DISEASE PROGRESSION; ANIMAL-MODEL; MOUSE MODEL; ALS MICE;

D O I：

10.1093/hmg/ddq293

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, neurodegenerative disease characterized by the loss of motor neurons. Motor neuron degeneration is probably both a cell autonomous and a non-autonomous event. Therefore, manipulating the diseased microenvironment via non-neural cell replacement could be a therapeutic strategy. We investigated a cell therapy approach using intravascular injection to transplant a specific population of c-kit(+) stem/progenitor cells from bone marrow into the SOD1G93A mouse model of ALS. Transplanted cells engrafted within the host spinal cord. Cell transplantation significantly prolonged disease duration and lifespan in superoxide dismutase 1 mice, promoted the survival of motor neurons and improved neuromuscular function. Neuroprotection was mediated by multiple effects, in particular by the expression of primary astrocyte glutamate transporter GLT1 and by the non-mutant genome. These findings suggest that this type of somatic cell transplantation strategy merits further investigation as a possible effective therapy for ALS and other neurodegenerative diseases.

引用

页码：3782 / 3796

页数：15

共 58 条

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