Electrospun nanofibrous scaffolds increase the efficacy of stem cell-mediated therapy of surgically resected glioblastoma.
Electrospun nanofibrous scaffolds increase the efficacy of stem cell-mediated therapy of surgically resected glioblastoma.
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DOI：
10.1016/j.biomaterials.2016.03.008
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发表时间：
2016-06
期刊：
影响因子：
14
通讯作者：
Hingtgen SD
中科院分区：
文献类型：
--
作者：
Bagó JR;Pegna GJ;Okolie O;Mohiti-Asli M;Loboa EG;Hingtgen SD
基于工程干细胞（SC）的治疗为治疗无法治愈的脑癌胶质母细胞瘤（GBM）带来了巨大的希望。在GBM切除后将细胞毒性SC保留在手术腔中是这种方法的最大挑战之一。在这里，我们描述了一种生物相容性静电纺丝纳米纤维支架（bENS）植入物，能够提供和保留肿瘤归巢细胞毒性干细胞，抑制术后GBM复发。作为GBM治疗的一种新方法，我们创建了聚（l-乳酸）（PLA）bENS载药释放人间充质干细胞（hMSCs）。我们发现，与使用我们的GBM手术切除/复发的小鼠模型的标准直接注射相比，基于bENS的植入物使hMSC在手术腔中的保留增加了5倍，并且使持久性延长了3倍。延时成像显示细胞毒性hMSC/bENS处理杀死了共培养的人GBM细胞，并允许hMSC在它们归巢到GBM时快速迁移离开支架。在体内，bENS负载hMSC释放抗肿瘤蛋白TRAIL（bENSsTR）减少了3倍的建立GBM异种移植物的体积。模拟临床GBM患者治疗，用bENSsTR植入物衬在术后GBM手术腔中抑制了残余GBM病灶的再生长2.3倍，并将小鼠的术后中位生存期从13.5天延长至31天。这些结果表明，基于纳米纤维的SC疗法可能是一种创新的新方法，可以改善晚期脑癌患者的预后。
Engineered stem cell (SC)-based therapy holds enormous promise for treating the incurable brain cancer glioblastoma (GBM). Retaining the cytotoxic SCs in the surgical cavity after GBM resection is one of the greatest challenges to this approach. Here, we describe a biocompatible electrospun nanofibrous scaffold (bENS) implant capable of delivering and retaining tumor-homing cytotoxic stem cells that suppress recurrence of post-surgical GBM. As a new approach to GBM therapy, we created poly(l-lactic acid) (PLA) bENS bearing drug-releasing human mesenchymal stem cells (hMSCs). We discovered that bENS-based implant increased hMSC retention in the surgical cavity 5-fold and prolonged persistence 3-fold compared to standard direct injection using our mouse model of GBM surgical resection/recurrence. Time-lapse imaging showed cytotoxic hMSC/bENS treatment killed co-cultured human GBM cells, and allowed hMSCs to rapidly migrate off the scaffolds as they homed to GBMs. In vivo, bENS loaded with hMSCs releasing the anti-tumor protein TRAIL (bENSsTR) reduced the volume of established GBM xenografts 3-fold. Mimicking clinical GBM patient therapy, lining the post-operative GBM surgical cavity with bENSsTR implants inhibited the re-growth of residual GBM foci 2.3-fold and prolonged post-surgical median survival from 13.5 to 31 days in mice. These results suggest that nanofibrous-based SC therapies could be an innovative new approach to improve the outcomes of patients suffering from terminal brain cancer.