首次将脐带血干细胞分化为大脑少突胶质细胞

2012-01-29 MedSci MedSci原创

脐带血干细胞有史以来第一次被转化为其他类型细胞,即大脑少突胶质细胞(oligodendrocyte),从而可能最终导致人们为脊髓损伤和多发性硬化症以及其他中枢神经系统疾病开发出新的治疗方法。 美国中佛罗里达大学(University of Central Florida)工程师James Hickman领导的一个研究小组在2012年1月18日那期ACS Chemical Neuroscience

脐带血干细胞有史以来第一次被转化为其他类型细胞,即大脑少突胶质细胞(oligodendrocyte),从而可能最终导致人们为脊髓损伤和多发性硬化症以及其他中枢神经系统疾病开发出新的治疗方法。

美国中佛罗里达大学(University of Central Florida)工程师James Hickman领导的一个研究小组在2012年1月18日那期ACS Chemical Neuroscience期刊上发表这一研究成就。他说,“这是第一次利用非胚胎性干细胞(non-embryonic stem cell)开展这项研究。我们对这项研究的最终意义感到非常激动,因为它克服了胚胎干细胞存在的很多障碍。”

脐带血干细胞不会产生伦理困境,因为它们来自被丢弃的脐带。另一个大的益处是人们已经发现脐带细胞并不导致免疫反应,这可能简化它们在医学治疗中的潜在应用。

位于美国加州门洛帕克市的制药公司Geron为脊髓修复开发出一种基于胚胎干细胞的治疗方法,但是它花费了18个月才得到来自美国食品药品管理局的批准进行人类临床试验,这其中大部分原因在于与人胚胎干细胞研究相关联的伦理和大众担忧。这种原因和其他问题最近导致该公司关闭了它的干细胞部门,从而突出表明人们需要其他的替代性治疗。

敏感性细胞

研究干细胞的主要挑战就是找出将它们转化为某种特定类型细胞的化学或其他触发物。当这篇新论文的通信作者Hedvika Davis着手研究将脐带干细胞转化为少突胶质细胞---用来隔绝大脑和脊髓中神经元的关键性结构细胞---时,她从过去研究中寻找线索。

Davis了解到其他研究小组早已发现少突胶质细胞上的组分与激素去甲肾上腺素(norepinephrine)结合,从而意味着这种细胞正常情况下与这种化学物相互作用,以及它可能是刺激它们产生的众多因子之一。因此,她决定这将是一个好的起点。

在早期测试中,她发现去甲肾上腺素与其他干细胞生长促进剂一起导致脐带干细胞转化或者说分化为少突胶质前体细胞(oligodendrocyte precursor) 。然而,这种转化也只是走这么远了。这些细胞虽然能够生长,但是它们不能成功达到类似于人中枢神经系统中发现那样的水平。

Davis判断,除了化学物外,物理环境可能也是至关重要的。

为了更加接近于身体中细胞所面临的物理限制,Davis构造了一种更加受限的三维环境,在显微镜载片顶端培养细胞,不过在培养的细胞上面还放置一块玻璃载片。只有做出这种变化后,再提供去甲肾上腺素和其他化学物,这些细胞完全成长为少突胶质细胞。

Davis说,“我们认识到这些干细胞对环境条件非常敏感。”

医学潜力

培养少突胶质细胞,尽管至关重要,但是也只是潜在性医学治疗的第一步。研究小组希望通过进一步研究探索两种主要的治疗方法。第一种就是将这些细胞在脊髓损伤的某个位点注射进身体从而促进修复。

就Hickman研究小组的研究而言,另一种有趣的可能性就是与多发性硬化症和类似症状相关联。

少突胶质细胞产生用来隔离神经细胞的髓鞘质(myelin),使得它们传导指导运动和其他功能的电信号成为可能。髓鞘质缺失导致多发性硬化症和诸如糖尿病性神经病变(diabetic neuropathy)之类的其他相关症状。

注射新的和健康的少突胶质细胞有可能改善遭受这些疾病折磨的病人的症状。研究小组也正希望开发出用来在实验室培养少突胶质细胞的技术,这样就将它们用作模式系统以便更好地理解髓鞘质的丢失和恢复和测试新的潜在性治疗方法。

Hickman说,“我们想要开展这两项实验。我们想要使用一种模式系统理解正在发生的事情,以及寻找可能的疗法修复一些损伤。我们想这两个方向存在较大的潜力。”(生物谷:towersimper编译)

Small Molecule Induction of Human Umbilical Stem Cells into Myelin Basic Protein Positive Oligodendrocytes in a Defined Three-Dimensional Environment

Hedvika Davis, Xiufang Guo, Stephen Lambert, Maria Stancescu, and James J. Hickman

Umbilical cord stem cells would be a favorable alternative to embryonic stem cells for therapeutic applications. In this study, human multipotent progenitor cells (MLPCs) from umbilical cord were differentiated into oligodendrocytes by being exposed to a range of microenvironmental chemical and physical cues. Chemical cues were represented by a novel defined differentiation medium containing the neurotransmitter norepinephrine (NE). Under traditional two-dimensional conditions, the MLPCs differentiated into oligodendrocyte precursors but did not progress further. However, in a three-dimensional environment, the MLPCs differentiated into committed oligodendrocytes that expressed myelin basic protein. The apparent method of interaction of NE in stimulating the differentiation process was shown to occur through the adenergic pathway, while all prior differentiation methods have used other routes. This novel method of obtaining functional human oligodendrocytes from MLPCs would eliminate many of the difficulties associated with their differentiation from embryonic stem cells.

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    2012-02-13 kevser

    It's a relief to find someone who can explain tinhgs so well

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