Stem cell therapy for white matter disorders: don't forget the microenvironment!
Stem cell therapy for white matter disorders: don't forget the microenvironment!
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DOI：
10.1007/s10545-016-9925-1
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发表时间：
2016-07
影响因子：
4.2
通讯作者：
Heine VM
中科院分区：
文献类型：
--
作者：
Dooves S;van der Knaap MS;Heine VM
白质疾病（WMD）是所有年龄段的障碍的主要来源。它们常常导致进行性神经功能障碍和过早死亡。尽管病因多种多样，但大规模杀伤性武器的共同特点是，神经胶质细胞（星形胶质细胞和少突胶质细胞）是主要受影响的细胞，而且髓鞘质要么不形成，要么丢失。许多大规模杀伤性武器可能受益于细胞替代疗法。啮齿动物模型的成功临床前研究已经导致首次在人体中使用神经胶质细胞或少突胶质细胞祖细胞进行髓鞘化（再）化试验。然而，髓磷脂通常不是唯一受影响的结构。神经元、小胶质细胞和星形胶质细胞也经常受到影响，它们都是为白质修复创造适当条件的重要伙伴。细胞外环境的组成是另一个需要考虑的因素。因此，细胞移植疗法可能需要纳入非少突胶质细胞类型，并且不仅仅针对髓磷脂修复。 WMD 患者可能会受益于多模式治疗方法，包括干细胞移植和微环境靶向策略，以将局部环境改变为更有利于细胞替代的状态。此外，大多数概念验证研究都是在啮齿动物疾病模型中使用人类细胞进行的。由于人类神经胶质细胞比宿主小鼠大脑中的小鼠神经胶质细胞表现出更大的再生能力，因此在啮齿动物研究中可能会忽视影响白质恢复的微环境因素。我们想强调的是，细胞替代疗法是大规模杀伤性武器的一种非常有前途的治疗选择，但接受的微环境至关重要。
White matter disorders (WMDs) are a major source of handicap at all ages. They often lead to progressive neurological dysfunction and early death. Although causes are highly diverse, WMDs share the property that glia (astrocytes and oligodendrocytes) are among the cells primarily affected, and that myelin is either not formed or lost. Many WMDs might benefit from cell replacement therapies. Successful preclinical studies in rodent models have already led to the first clinical trials in humans using glial or oligodendrocyte progenitor cells aiming at (re)myelination. However, myelin is usually not the only affected structure. Neurons, microglia, and astrocytes are often also affected and are all important partners in creating the right conditions for proper white matter repair. Composition of the extracellular environment is another factor to be considered. Cell transplantation therapies might therefore require inclusion of non-oligodendroglial cell types and target more than only myelin repair. WMD patients would likely benefit from multimodal therapy approaches involving stem cell transplantation and microenvironment-targeting strategies to alter the local environment to a more favorable state for cell replacement. Furthermore most proof-of-concept studies have been performed with human cells in rodent disease models. Since human glial cells show a larger regenerative capacity than their mouse counterparts in the host mouse brain, microenvironmental factors affecting white matter recovery might be overlooked in rodent studies. We would like to stress that cell replacement therapy is a highly promising therapeutic option for WMDs, but a receptive microenvironment is crucial.