Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: Distribution, migration, and differentiation

被引:227
作者
Garbuzova-Davis, S
Willing, AE
Zigova, T
Saporta, S
Justen, EB
Lane, JC
Hudson, JE
Chen, N
Davis, CD
Sanberg, PR
机构
[1] Univ S Florida, Coll Med, Ctr Aging & Brain Repair, Dept Neurosurg, Tampa, FL 33612 USA
[2] Univ S Florida, Coll Med, Ctr Excellence Aging & Brain Repair, Tampa, FL 33612 USA
[3] Univ S Florida, Coll Med, Dept Anat, Tampa, FL 33612 USA
[4] Univ S Florida, Coll Med, Dept Pharm & Therapeut, Tampa, FL 33612 USA
[5] Univ S Florida, Coll Med, Dept Psychiat, Tampa, FL 33612 USA
[6] Univ S Florida, Coll Med, Dept Pathol, Tampa, FL 33612 USA
[7] USF Ctr Entrepreneurship, Saneron CCEL Therapeut Inc, Temple Terrace, FL 33617 USA
来源
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH | 2003年 / 12卷 / 03期
关键词
D O I
10.1089/152581603322022990
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Amyotrophic lateral sclerosis (ALS), a multifactorial disease characterized by diffuse motor neuron degeneration, has proven to be a difficult target for stem cell therapy. The primary aim of this study was to determine the long-term effects of intravenous mononuclear human umbilical cord blood cells on disease progression in a well-defined mouse model of ALS. In addition, we rigorously examined the distribution of transplanted cells inside and outside the central nervous system (CNS), migration of transplanted cells to degenerating areas in the brain and spinal cord, and their immunophenotype. Human umbilical cord blood (hUCB) cells (10(6)) were delivered intravenously into presymptomatic G93A mice. The major findings in our study were that cord blood transfusion into the systemic circulation of G93A mice delayed disease progression at least 2-3 weeks and increased lifespan of diseased mice. In addition, transplanted cells survived 10-12 weeks after infusion while they entered regions of motor neuron degeneration in the brain and spinal cord. There, the cells migrated into the parenchyma of the brain and spinal cord and expressed neural markers [Nestin, III Beta-Tubulin (TuJ1), and glial fibrillary acidic protein (GFAP)]. Infused cord blood cells were also widely distributed in peripheral organs, mainly the spleen. Transplanted cells also were recovered in the peripheral circulation, possibly providing an additional cell supply. Our results indicate that cord blood may have therapeutic potential in this noninvasive cell-based treatment of ALS by providing cell replacement and protection of motor neurons. Replacement of damaged neurons by progeny of cord blood stem cells is probably not the only mechanism by which hUCB exert their effect, since low numbers of cells expressed neural antigens. Most likely, cord blood efficacy is partially due to neuroprotection by modulation of the autoimmune process.
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收藏
页码:255 / 270
页数:16
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