Neuroscience Research Laboratories, Department of Neurosurgery, VA Medical Center - Research 151, 5000 West National Avenue, Milwaukee, Wisconsin, WI 53295, USA.
Regen Med. 2010 Nov;5(6):891-900. doi: 10.2217/rme.10.67.
Stem cell-based therapies to repair and replace lost neural cells are a highly promising treatment for CNS diseases. Bone marrow (BM)-derived mesenchymal stem cells (MSCs) have great potential as therapeutic agents against neurological maladies, since they have the ability to differentiate into neural phenotypes and can be readily isolated and expanded for autotransplantation with no risk of rejection. In our previous studies, we demonstrated that neural cells could be efficiently generated from mouse BM-derived MSCs by exposing cells to epigenetic modifiers and a neural environment. The main idea of this approach was the reactivation of pluripotency-associated genes in MSCs before exposing them to neural-inducing factors.
In this study, we used a similar approach to efficiently generate neural cells from human BM-derived MSCs.
Neural induction was achieved by exposing cells simultaneously to inhibitors of DNA methylation and histone deacetylation, and pharmacological agents that increase cAMP levels.
The expression of pluripotency and neural markers was confirmed with immunocytochemistry, western blot and real-time PCR. ELISA studies showed that these neurally induced-human MSCs cells released the neurotrophic factors glial cell-derived neurotrophic factor and brain-derived neurotrophic factor.
Human MSCs that are neurally modified with this methodology could be a useful source of cells for CNS repair and regeneration.
基于干细胞的疗法，用于修复和替换丢失的神经细胞，是治疗中枢神经系统疾病的一种极具前景的方法。骨髓（BM）来源的间充质干细胞（MSCs）作为治疗神经疾病的潜在治疗剂具有巨大的潜力，因为它们具有分化为神经表型的能力，并且可以很容易地分离和扩增，用于自体移植，没有排斥的风险。在我们之前的研究中，我们证明了通过将细胞暴露于表观遗传修饰剂和神经环境中，可以从鼠 BM 来源的 MSC 中有效地生成神经细胞。这种方法的主要思路是在将 MSC 暴露于神经诱导因子之前，重新激活与多能性相关的基因。
在本研究中，我们使用类似的方法，从人 BM 来源的 MSC 中高效地生成神经细胞。
通过同时将细胞暴露于 DNA 甲基化和组蛋白去乙酰化抑制剂以及增加 cAMP 水平的药物来实现神经诱导。
通过免疫细胞化学、Western blot 和实时 PCR 证实了多能性和神经标记物的表达。ELISA 研究表明，这些诱导的人 MSC 细胞释放神经营养因子胶质细胞源性神经营养因子和脑源性神经营养因子。
用这种方法神经修饰的人 MSC 可以成为中枢神经系统修复和再生的有用细胞来源。
