胶质母细胞瘤是侵袭性最强的恶性原发性脑肿瘤,预后不佳,总体生存率毁灭性。尽管积极的手术切除和辅助治疗,平均生存期约为14.6个月。脑肿瘤微环境是异质的,包括多个肿瘤群体,基质,和免疫细胞。肿瘤细胞通过抑制几种免疫功能来逃避免疫系统以实现存活。胶质瘤释放免疫抑制和肿瘤支持性可溶性因子进入微环境,导致癌症加速扩散,入侵,免疫逃逸。间充质干细胞(MSCs)分离自骨髓,脂肪组织,或脐带是基于细胞的疗法的有前途的工具。在MSC应用中经常看到的介导治疗结果的一个关键机制是它们对损伤部位的向性。此外,MSCs与宿主免疫细胞相互作用调节炎症反应,和数据表明使用MSCs在实体瘤中实现免疫调节的可能性。白细胞介素1β,白细胞介素6,肿瘤坏死因子α,转化生长因子β,和基质细胞衍生因子1在胶质母细胞瘤中显著上调,并双重促进免疫和MSC运输。间充质干细胞已被广泛认为是低免疫原性,使这种基于细胞的管理能够跨越主要的组织相容性障碍。在这次审查中,我们将强调(1)神经胶质瘤细胞和肿瘤相关免疫细胞的双向通信,(2)炎症介质使白细胞和可移植的MSC迁移,和(3)回顾使用MSC作为递送载体的临床前和人类临床试验。间充质干细胞具有迁移远距离的先天能力,穿过血脑屏障,并与周围的细胞交流,所有这些都使他们成为脑癌治疗的理想“特洛伊木马”。
Glioblastoma is the most aggressive malignant primary brain tumor, with a dismal prognosis and a devastating overall survival. Despite aggressive surgical resection and adjuvant treatment, average survival remains approximately 14.6 months. The brain tumor microenvironment is heterogeneous, comprising multiple populations of tumor, stromal, and immune cells. Tumor cells evade the immune system by suppressing several immune functions to enable survival. Gliomas release immunosuppressive and tumor-supportive soluble factors into the microenvironment, leading to accelerated cancer proliferation, invasion, and immune escape. Mesenchymal stem cells (MSCs) isolated from bone marrow, adipose tissue, or umbilical cord are a promising tool for cell-based therapies. One crucial mechanism mediating the therapeutic outcomes often seen in MSC application is their tropism to sites of injury. Furthermore, MSCs interact with host immune cells to regulate the inflammatory response, and data points to the possibility of using MSCs to achieve immunomodulation in solid tumors. Interleukin 1β, interleukin 6, tumor necrosis factor α, transforming growth factor β, and stromal cell-derived factor 1 are notably up-regulated in glioblastoma and dually promote immune and MSC trafficking. Mesenchymal stem cells have widely been regarded as hypoimmunogenic, enabling this cell-based administration across major histocompatibility barriers. In this review, we will highlight (1) the bidirectional communication of glioma cells and tumor-associated immune cells, (2) the inflammatory mediators enabling leukocytes and transplantable MSC migration, and (3) review preclinical and human clinical trials using MSCs as delivery vehicles. Mesenchymal stem cells possess innate abilities to migrate great distances, cross the blood-brain barrier, and communicate with surrounding cells, all of which make them desirable \"Trojan horses\" for brain cancer therapy.