King Jasmine L, Valdivia Alain, Hingtgen Shawn D, Benhabbour S Rahima
Joint Department of Biomedical Engineering, The University of North Carolina at Chapel Hill and North Carolina State University, Chapel Hill, NC 27599, USA.
Division of Pharmacoengineering and Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Pharmaceutics. 2024 Dec 24;17(1):3. doi: 10.3390/pharmaceutics17010003.
BACKGROUND/OBJECTIVES: Glioblastoma multiforme (GBM) is the most common high-grade primary brain cancer in adults. Despite efforts to advance treatment, GBM remains treatment resistant and inevitably progresses after first-line therapy. Induced neural stem cell (iNSC) therapy is a promising, personalized cell therapy approach that has been explored to circumvent challenges associated with the current GBM treatment.
Herein, we developed a chitosan-based (CS) injectable, biodegradable, in situ forming thermo-responsive hydrogel as a cell delivery vehicle for the treatment of GBM. Tumoricidal neural stem cells were encapsulated in the injectable CS hydrogel as stem cell therapy for treatment of post-surgical GBM. In this report, we investigated the safety of the injectable CS hydrogel in an immune-competent mouse model. Furthermore, we evaluated the persistence and efficacy of iNSC-laden CS hydrogels in a post-surgical GBM mouse model.
The injectable CS hydrogel was well tolerated in mice with no signs of chronic local inflammation. Induced neural stem cells (iNSCs) persisted in the CS hydrogels for over 196 days in comparison to 21 days for iNSCs (cell injection) only. GBM recurrence was significantly slower in mice treated with iNSC-laden CS hydrogels with a 50% increase in overall median survival in comparison to iNSCs (cell injection) only.
Collectively, we demonstrated the ability to encapsulate, retain, and deliver iNSCs in an injectable CS hydrogel that is well tolerated with better survival rates than iNSCs alone.
背景/目的：多形性胶质母细胞瘤（GBM）是成人中最常见的高级原发性脑癌。尽管在推进治疗方面做出了努力，但GBM仍然具有治疗抗性，并且在一线治疗后不可避免地会进展。诱导神经干细胞（iNSC）疗法是一种有前景的个性化细胞疗法，已被探索用于规避当前GBM治疗相关的挑战。
在此，我们开发了一种基于壳聚糖（CS）的可注射、可生物降解、原位形成的热响应水凝胶，作为治疗GBM的细胞递送载体。将具有杀肿瘤作用的神经干细胞封装在可注射的CS水凝胶中，作为治疗手术后GBM的干细胞疗法。在本报告中，我们在具有免疫能力的小鼠模型中研究了可注射CS水凝胶的安全性。此外，我们在手术后GBM小鼠模型中评估了负载iNSC的CS水凝胶的持久性和疗效。
可注射的CS水凝胶在小鼠中耐受性良好，没有慢性局部炎症的迹象。与仅注射iNSC（细胞注射）的情况相比，诱导神经干细胞（iNSC）在CS水凝胶中持续存在超过196天，而iNSC仅持续21天。与仅注射iNSC（细胞注射）相比，用负载iNSC的CS水凝胶治疗的小鼠中GBM复发明显较慢，总体中位生存期增加了50%。
总体而言，我们证明了在可注射的CS水凝胶中封装、保留和递送iNSC的能力，该水凝胶耐受性良好，生存率比单独的iNSC更好。
