Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: Distribution, migration, and differentiation
Intravenous administration of human umbilical cord blood cells in a mouse model of amyotrophic lateral sclerosis: Distribution, migration, and differentiation
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DOI：
10.1089/152581603322022990
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发表时间：
2003-06-01
期刊：
影响因子：
--
通讯作者：
Sanberg, PR
中科院分区：
文献类型：
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作者：
Garbuzova-Davis, S;Willing, AE;Sanberg, PR
肌萎缩侧索硬化症（ALS）是一种以弥漫性运动神经元变性为特征的多因素疾病，已被证明是干细胞治疗的一个困难靶点。本研究的主要目的是确定静脉内单个人脐带血细胞对明确定义的ALS小鼠模型中疾病进展的长期影响。此外，我们严格检查了移植细胞在中枢神经系统（CNS）内外的分布，移植细胞向脑和脊髓退化区域的迁移，以及它们的免疫表型。将人脐带血（hUCB）细胞（10（6））静脉内递送到症状前G93 A小鼠中。我们研究的主要发现是，将脐带血输注到G93 A小鼠的体循环中至少延迟了疾病进展2-3周，并延长了患病小鼠的寿命。此外，移植的细胞在输注后存活了10-12周，同时它们进入了大脑和脊髓中的运动神经元变性区域。在那里，细胞迁移到脑和脊髓的实质中并表达神经标记物[巢蛋白、III β-微管蛋白（TuJ 1）和胶质细胞酸性蛋白（GFAP）]。输注的脐带血细胞也广泛分布于外周器官，主要是脾脏。移植的细胞也在外周循环中回收，可能提供额外的细胞供应。我们的研究结果表明，脐带血可能具有治疗潜力，在这种非侵入性的细胞为基础的治疗ALS提供细胞替代和运动神经元的保护。脐带血干细胞后代替代受损神经元可能不是hUCB发挥作用的唯一机制，因为表达神经抗原的细胞数量很少。最有可能的是，脐带血的疗效部分是由于调节自身免疫过程的神经保护作用。
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.