دوره 37، شماره 535: هفته سوم شهریور ماه 1398:845-856

کاربرد کشت سه ‌بعدی در بهینه‌سازی تحقیقات دارویی سرطان: از روش‌های سنتی تا تکنولوژی نوین میکروسیالی

شبنم شهریوری , زینب باقری , ندا سرای گرد افشاری , حمید لطیفی

DOI: 10.22122/jims.v37i535.11883

چکیده


با وجود هزینه‌های هنگفت و زمان بسیاری که در مراحل پیش کارآزمایی‌های بالینی صرف می‌شود، بیش از نیمی از فراورده‌های دارویی به دلیل عدم اثربخشی یا بروز عوارض جانبی از چرخه‌ی تولید حذف می‌گردند. این در حالی ‌است که بروز مقاومت‌های دارویی و تفاوت‌های فردی، در بیماری‌های پیچیده‌ای همچون سرطان و نیز گسترش روزافزون مفهوم پزشکی شخصی، نیاز به ارایه‌ی مدل‌های کارآمد و مؤثر را در بررسی‌های دارویی بیش از پیش نمایان می‌سازد. کشت‌های سلولی، ابزارهای مهمی بررسی‌های دارویی هستند که در مراحل پیش‌ کارآزمایی ‌بالینی به ‌طور گسترده مورد استفاده قرار می‌گیرند. امروزه، مسجل شده است که سهم عظیمی از عدم موفقیت مراحل پیش ‌کارآزمایی‌ بالینی به عدم موفقیت کشت‌های سلولی در شبیه‌سازی شرایط بدن بر می‌گردد. به همین دلیل، امروزه ظهور کشت‌های سه‌ بعدی، پنجره‌ای جدید را به روی مطالعات دارویی گشوده است. مطالعات متعددی نشان می‌دهند که شیوه‌های نوین کشت سلول با توانایی شبیه‌سازی تعاملات سلول-سلول، سلول- ماتریکس و ایجاد شیب غلظت دارو، اکسیژن، متابولیت‌ها و مواد غذایی، مشابه با شرایط بدن، به‌ طور مستقیم یا غیر مستقیم (از طریق تأثیرگذاری بر بیان ژن‌ها و ایجاد فنوتیپ طبیعی)، مطالعات دارویی را قابل اعتمادتر کرده‌ است. به تازگی، برای تطابق بیشتر با بدن، از کشت‌های سه بعدی در تراشه‌های میکروسیالی نیز استفاده می‌شود. ریزتراشه‌ها، به دلیل اندازه‌ی نزدیک به سلول‌ها و عروق بدن، امکان کشت سلول به شیوه‌ی پویا و غیره، شباهت بیشتری با بدن فراهم می‌کنند. در مقاله‌ی پیش‌رو، ضمن مروری بر روش‌های مختلف کشت سه ‌بعدی، کاربردهای آن در مطالعات دارویی نیز مطرح می‌گردد.


واژگان کلیدی


سرطان؛ ریزتراشه میکروسیالی؛ کشت سلولی؛ توسعه و کشف فراورده‌ی دارو

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