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

نوع مقاله : مقاله مروری

نویسندگان

1 گروه زیست‌فن‌آوری پزشکی، دانشکده‌ی پیراپزشکی، دانشگاه علوم پزشکی ایران، تهران، ایران

2 استادیار، گروه مهندسی زیستی و زیست نانو فن‌آوری، دانشکده‌ی علوم و فن‌آوری‌های زیستی، دانشگاه شهید بهشتی، تهران، ایران

3 استادیار، گروه زیست‌ فن‌آوری پزشکی، دانشکده‌ی پیراپزشکی، دانشگاه علوم پزشکی ایران، تهران، ایران

4 استاد، پژوهشکده‌ی لیزر و پلاسما، دانشگاه شهید بهشتی، تهران، ایران

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.

کلیدواژه‌ها

عنوان مقاله [English]

Three-Dimensional Cell Cultures in Anticancer Drug Researches: From Traditional Methods to Emerging Microfluidic Technology

نویسندگان [English]

  • Shabnam Shahrivari 1
  • Zeinab Bagheri 2
  • Neda Saraygord-Afshari 3
  • Hamid Latifi 4
1 Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
2 Assistant Professor, Department of Biology Engineering and Nanotechnology, School of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
3 Assistant Professor, Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
4 Professor, Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran
چکیده [English]

Despite the expensive and time-consuming pre-clinical assessments, more than 50% of medicines fail to reach manufacturing cycle due to the low therapeutic index or possible side effects. Moreover, the challenge of drug resistance and person-to-person variation in complex diseases, such as cancer, and the growing concept of personalized medicine has also made a strong demand for more reliable pre-clinical drug assessment models. Cell culture is an essential and widely-used model in pre-clinical trials, but today we know that traditional culture methods fail to mimic the real in-vivo microenvironment, and hence they are proven to be responsible for the trails’ failure. It seems that the problem is going to be solved by the advent of three-dimentional (3D)-cell culture systems in which cell-cell and cell-matrix interaction, as well as the gradients of drugs, oxygen, metabolites, and nutrients, are well designed to efficiently mimic natural conditions, and provide more reliable results for drug assessments. A variety of researchers have purposed that this new paradigm, either directly or indirectly (by affecting gene expression and inducing natural phenotypes), affect cell behavior to meet the challenge of pre-clinical and clinical inconsistency. Recently, 3D-cultures on microfluidic platforms are used to provide a higher level of adaptation to living bodies. Due to the comparable similarity between microchips and living cells scales as well as the body vessels, besides the possibility to run a dynamic culture situation with real physical tension, etc. they are more potent to mimic actual in vivo microenvironment. Therefore, here, we are going to review various models of 3D-cell culture systems, and discuss their impact on pharmaceutical researches.

کلیدواژه‌ها [English]

  • Cancer
  • Microfluidic microchips
  • Cell culture
  • Drug discovery

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مجله دانشکده پزشکی اصفهان
دوره 37، شماره 535 - شماره پیاپی 535
مرداد و شهریور 1398
صفحه 845-856

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  • تاریخ دریافت: 12 خرداد 1398
  • تاریخ بازنگری: 11 آبان 1403
  • تاریخ پذیرش: 17 فروردین 1401

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