Lund Stem Cell Center, Lund University, Lund, Sweden.
Neurosurgery. 2012 Mar;70(3):731-9. doi: 10.1227/NEU.0b013e318232dedd.
Viral gene therapy of malignant brain tumors has been restricted by the limited vector distribution within the tumors. Multipotent mesenchymal stromal cells (MSCs) and other precursor cells have shown tropism for gliomas, and these cells are currently being explored as potential vehicles for gene delivery in glioma gene therapy.
To investigate MSC migration in detail after intratumoral and extratumoral implantation through syngeneic and orthotopic glioma models.
Adult rat bone marrow-derived MSCs were transduced to express enhanced green fluorescent protein and implanted either directly into or at a distance from rat gliomas.
We found no evidence of long-distance MSC migration through the intact striatum toward syngeneic D74(RG2), N32, and N29 gliomas in the ipsilateral hemisphere or across the corpus callosum to gliomas located in the contralateral hemisphere. After intratumoral injection, MSCs migrated extensively, specifically within N32 gliomas. The MSCs did not proliferate within tumors, suggesting a low risk of malignant transformation of in vivo grafted cell vectors. Using a model for surgical glioma resection, we found that intratumorally grafted MSCs migrate efficiently within glioma remnants after partial surgical resection.
The findings point to limitations for the use of MSCs as vectors in glioma gene therapy, although intratumoral MSC implantation provides a dense and tumor-specific vector distribution.
恶性脑肿瘤的病毒基因治疗受到肿瘤内载体分布有限的限制。多能间充质基质细胞（MSCs）和其他前体细胞对神经胶质瘤具有趋向性，这些细胞目前正在作为神经胶质瘤基因治疗中基因传递的潜在载体进行探索。
通过同基因和原位神经胶质瘤模型，详细研究 MSC 肿瘤内和肿瘤外植入后的迁移情况。
将成年大鼠骨髓源性 MSC 转导表达增强型绿色荧光蛋白，并直接植入或远离大鼠神经胶质瘤。
我们没有发现 MSC 经完整纹状体向同侧半球的同基因 D74（RG2）、N32 和 N29 神经胶质瘤或穿过胼胝体向对侧半球的神经胶质瘤进行长距离迁移的证据。肿瘤内注射后，MSC 广泛迁移，特别是在 N32 神经胶质瘤内。MSC 未在肿瘤内增殖，提示体内移植细胞载体恶性转化的风险较低。使用手术切除神经胶质瘤的模型，我们发现部分手术切除后，肿瘤内移植的 MSC 能够在神经胶质瘤残体中有效迁移。
这些发现表明，尽管肿瘤内 MSC 植入可提供密集且肿瘤特异性的载体分布，但 MSCs 作为神经胶质瘤基因治疗载体的应用受到限制。
