Neuroscience Research Labs, Deptpartment of Neurosurgery, Medical College of Wisconsin, VAMC, Milwaukee, WI 53295, USA.
Restor Neurol Neurosci. 2010;28(6):761-7. doi: 10.3233/RNN-2010-0547.
We recently developed a new method for efficient generation of neural-like cells from mice bone marrow (BM)-derived mesenchymal stem cells (MSC) by exposing MSCs to epigenetic modifiers and a neural stem cell environment. These neurally induced MSCs (NI-MSCs) differentiate into neuronal- and glial-like cells in vitro, release neurotrophic factors NGF and BDNF, survive and integrate after transplantation in intact spinal cord. The aim of this study was to determine whether transplanted NI-MSCs survive, differentiate, and integrate in injured spinal cord (ISC) rats and promote functional recovery.
Twenty rats, half grafted with MSCs and half with NI-MSCs, were used for survival and differentiation studies. Results were analyzed using triple-labeled immunohistochemistry. For motor function studies the 3 group of adult female Sprague Dawley rats received PBS (vehicle), MSCs, or NI-MSCs, respectively. Functional outcome was measured using the BBB scale.
Results demonstrated gradual improvement of locomotor function in NI-MSC-transplanted rats in comparison to vehicle and non-modified MSC-transplanted animals, with statistically significant differences at 7, 14, and 21 days post transplantation. Immunocytochemical studies revealed poor survival of NI-MSCs within the ISC as early as 3 weeks after transplantation.
Thus, there is a correlation between the degree of surviving NI-MSCs and extent of functional recovery.
我们最近开发了一种新方法，通过将骨髓（BM）衍生的间充质干细胞（MSC）暴露于表观遗传修饰剂和神经干细胞环境中，从鼠源性 MSC 高效生成神经样细胞。这些诱导的 MSC（NI-MSC）在体外分化为神经元样和神经胶质样细胞，释放神经营养因子 NGF 和 BDNF，在完整的脊髓中移植后存活并整合。本研究的目的是确定移植的 NI-MSC 是否在损伤的脊髓（ISC）大鼠中存活、分化和整合，并促进功能恢复。
20 只大鼠，一半移植 MSC，一半移植 NI-MSC，用于存活和分化研究。使用三标免疫组化分析结果。对于运动功能研究，3 组成年雌性 Sprague Dawley 大鼠分别接受 PBS（载体）、MSC 或 NI-MSC。使用 BBB 量表测量功能结果。
结果表明，与载体和非修饰 MSC 移植动物相比，NI-MSC 移植大鼠的运动功能逐渐改善，移植后 7、14 和 21 天的差异具有统计学意义。免疫细胞化学研究表明，NI-MSC 在移植后 3 周内就在 ISC 中存活不良。
因此，存活的 NI-MSC 程度与功能恢复程度之间存在相关性。
