Tế bào trung mô từ tủy xương người biểu hiện S-TRAIL như một phương tiện vận chuyển tế bào trong liệu pháp điều trị glioma ở người
Tóm tắt
U nguyên bào thần kinh là một trong những loại ung thư ở người có tính xâm lấn mạnh mẽ và kháng điều trị. Các phương pháp điều trị thông thường không thành công do sự xâm lấn lan tỏa của các tế bào u glioma vào mô não bình thường. Các liệu pháp dựa trên tế bào gốc cung cấp một cách tiếp cận đầy hứa hẹn cho việc điều trị glioma ác tính nhờ vào khả năng di cư của chúng vào các tế bào u xâm lấn. Chiến lược điều trị của chúng tôi là sử dụng tế bào trung mô lấy từ tủy xương người (hMSCs) như một phương tiện vận chuyển tế bào cho việc cung cấp có mục tiêu và sản xuất tại chỗ tác nhân sinh học có tên là ligand gây apoptosis liên quan đến yếu tố hoại tử u (TRAIL) tại vị trí khối u glioma. hMSCs đã được chuyển gen bằng lentivirus có khả năng tiết TRAIL (S-TRAIL) và mCherry (protein phát quang đỏ). Kết quả của chúng tôi cho thấy rõ khả năng duy trì tính chất hướng khối u của các tế bào hMSC S-TRAIL thông qua các xét nghiệm di cư in vitro và in vivo. Các xét nghiệm in vitro đã xác nhận sự biểu hiện, giải phóng và hoạt tính sinh học của S-TRAIL được sản xuất bởi các tế bào hMSC S-TRAIL. Để đánh giá hiệu quả điều trị in vivo, hMSCs được tiêm vào phía cùng bên với khối u glioma trong mô hình xenograft chuột. Các tế bào hMSC S-TRAIL đã được kỹ thuật gen cho thấy hiệu quả trong việc ức chế sự phát triển khối u U87 glioma trong sọ (81,6%) in vivo và dẫn đến việc sống lâu hơn cho động vật. Các nghiên cứu miễn dịch hóa học cho thấy có sự gia tăng đáng kể, gấp tám lần về apoptosis tế bào khối u trong nhóm điều trị bằng hMSC S-TRAIL so với nhóm chứng. Nghiên cứu của chúng tôi chứng minh hiệu quả điều trị của các tế bào hMSC S-TRAIL và xác nhận rằng hMSCs có thể hoạt động như một phương tiện vận chuyển tế bào mạnh mẽ cho việc giải phóng cụ thể tại vị trí các protein điều trị.
Từ khóa
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