Kanser Araştırmalarında Üç Boyutlu Doku Kültür Sistemlerinin Önemi
Özet
Üç boyutlu (3D) doku kültür sistemleri, iki boyutlu (2D) tek tabaka kültürlerin aksine, solid tümörlerin in vivo ortamdaki uzaysal konumunu, heterojen yapısını, hücre-hücre ve hücre-matriks etkileşimlerini gerçeğe yakın şekilde yansıtmaktadır. 2D kültürlerde besin ve oksijen eşit dağılırken, bu durum tümör karakteristiklerinin tam olarak ortaya konmasını engellemekte ve hücrelerin fenotipik özelliklerini kaybetmesine yol açmaktadır. 3D doku kültür sistemleri ise hayvan modelleri ile 2D kültürler arasındaki boşluğu doldurarak biyobelirteç geliştirme, ilaç metabolizması, patogenez, toksisite ve kanser kök hücrelerinin karakterizasyonu gibi alanlarda çok daha kesin ve güvenilir sonuçlar sunmaktadır. Yapılan çalışmalar, 3D sistemlerde büyütülen hücrelerin daha yüksek kimyasal dirence sahip olduğunu, protein ekspresyon seviyelerinde ve gen metilasyon imzalarında 2D yapılara kıyasla belirgin ve yapısal farklılıklar sergilediğini göstermektedir. Günümüzde bu modellerin oluşturulmasında; sferoid yapılar (sıvı üst tabaka, spinner flask ve sarmal dönüş yöntemleri), endüstriyel üretime uygun mikrotaşıyıcılar, sentetik ya da doğal polimerik matrisler (scaffold) ve NASA tarafından mikroyerçekimi ortamı yaratılarak minimal hidrodinamik kuvvetlerle geliştirilen rotatif hücre kültürü sistemi gibi her biri kendine has avantaj ve dezavantaj barındıran farklı teknikler etkin şekilde kullanılmaktadır.
Three-dimensional (3D) tissue culture systems, unlike two-dimensional (2D) monolayer cultures, realistically reflect the spatial location, heterogeneous structure, cell-cell, and cell-matrix interactions of solid tumors in the in vivo environment. While nutrients and oxygen are distributed equally in 2D cultures, this situation prevents tumor characteristics from being fully revealed and leads to the loss of phenotypic properties of cells. 3D tissue culture systems fill the gap between animal models and 2D cultures, offering much more precise and reliable results in fields such as biomarker development, drug metabolism, pathogenesis, toxicity, and the characterization of cancer stem cells. Studies demonstrate that cells grown in 3D systems possess higher chemical resistance and display distinct structural differences in protein expression levels and gene methylation signatures compared to 2D structures. Today, in the generation of these models; different techniques, each possessing its own advantages and disadvantages, are effectively utilized, such as spheroid structures (liquid overlay, spinner flask, and gyratory rotation methods), microcarriers suitable for industrial production, synthetic or natural polymeric matrices (scaffolds), and the rotary cell culture system developed by NASA by creating a microgravity environment with minimal hydrodynamic forces.
Referanslar
Lacroix, M.Persistent use of "false" cell lines. Int J Cancer,(2008); 122(1): p. 1-4.
Uygulamalı Hücre Kültürü Teknikleri Kursu, Kurs Kitabı I,. 2003. Süleyman Demirel Üniversitesi, Tıp Fakültesi, Histoloji ve Embriyoloji A.B.D.
Kim, J.B., R. Stein and M.J. O'Hare.Three-dimensional in vitro tissue culture models of breast cancer-- a review. Breast Cancer Res Treat,(2004); 85(3): p. 281-91.
Sukruoglu Erdogan, O., S. Kilic Erciyas, A. Bilir, et al.Methylation Changes of Primary Tumors, Monolayer, and Spheroid Tissue Culture Environments in Malignant Melanoma and Breast Carcinoma. Biomed Res Int,(2019); 2019: p. 1407167.
Xing, H., S. Wang, K. Hu, et al.Effect of the cyclin-dependent kinases inhibitor p27 on resistance of ovarian cancer multicellular spheroids to anticancer chemotherapy. J Cancer Res Clin Oncol,(2005); 131(8): p. 511-9.
Weaver, V.M., O.W. Petersen, F. Wang, et al.Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. J Cell Biol,(1997); 137(1): p. 231-45.
David, L., V. Dulong, D. Le Cerf, et al.Hyaluronan hydrogel: an appropriate three-dimensional model for evaluation of anticancer drug sensitivity. Acta Biomater,(2008); 4(2): p. 256-63.
Demiray S B, A.S., Oltulu F, Çavusoğlu T, Akarca Ö, Dilsiz Ö Y, Ergüven M, Öktem G, Bilir A.Apoptotic effects of chemotheraphy in the MDAH- 2774 ovarian cancer stem cell. Ege Journal of Medicine (2011); 50 (2): p. 103-109.
Campbell, J.J., N. Davidenko, M.M. Caffarel, et al.A multifunctional 3D co-culture system for studies of mammary tissue morphogenesis and stem cell biology. PLoS One,(2011); 6(9): p. e25661.
Smith, H.S., S.R. Wolman and A.J. Hackett.The biology of breast cancer at the cellular level. Biochim Biophys Acta,(1984); 738(3): p. 103-23.
Petersen, O.W., L. Ronnov-Jessen, A.R. Howlett, et al.Interaction with basement membrane serves to rapidly distinguish growth and differentiation pattern of normal and malignant human breast epithelial cells. Proc Natl Acad Sci U S A,(1992); 89(19): p. 9064-8.
Tsunoda, T., Y. Takashima, T. Fujimoto, et al.Three-dimensionally specific inhibition of DNA repair-related genes by activated KRAS in colon crypt model. Neoplasia,(2010); 12(5): p. 397-404.
Levin, V.A., S. Panchabhai, L. Shen, et al.Protein and phosphoprotein levels in glioma and adenocarcinoma cell lines grown in normoxia and hypoxia in monolayer and three-dimensional cultures. Proteome Sci,(2012); 10(1): p. 5.
Lai, Y., A. Asthana and W.S. Kisaalita.Biomarkers for simplifying HTS 3D cell culture platforms for drug discovery: the case for cytokines. Drug Discov Today,(2011); 16(7-8): p. 293-7.
Herreros-Pomares, A., X. Zhou, S. Calabuig-Farinas, et al.3D printing novel in vitro cancer cell culture model systems for lung cancer stem cell study. Mater Sci Eng C Mater Biol Appl,(2021); 122: p. 111914.
Glimelius, B., B. Norling, T. Nederman, et al.Extracellular matrices in multicellular spheroids of human glioma origin: increased incorporation of proteoglycans and fibronectin as compared to monolayer cultures. APMIS,(1988); 96(5): p. 433-44.
Fusenig, N.E., A. Limat, H.J. Stark, et al.Modulation of the differentiated phenotype of keratinocytes of the hair follicle and from epidermis. J Dermatol Sci,(1994); 7 Suppl: p. S142-51.
Kapalczynska, M., T. Kolenda, W. Przybyla, et al.2D and 3D cell cultures - a comparison of different types of cancer cell cultures. Arch Med Sci,(2018); 14(4): p. 910-919.
Nath, S. and G.R. Devi.Three-dimensional culture systems in cancer research: Focus on tumor spheroid model. Pharmacol Ther,(2016); 163: p. 94-108.
Moscona, A.A.How cells associate. Sci Am,(1961); 205: p. 142-62.
Öktem G, A.Ş., Tuna S, Baka M, Bilir A.Doksorubisinin Multisellüler Spheroid Hücre Kültürlerinde MCF-7 Hücreleri Üzerine Etkisi: Elektron mikroskobik Çalışma. Turkiye Klinikleri J Med Sci (2005); 25: p. 337-342.
Sutherland, R.M., W.R. Inch, J.A. McCredie, et al.A multi-component radiation survival curve using an in vitro tumour model. Int J Radiat Biol Relat Stud Phys Chem Med,(1970); 18(5): p. 491-5.
Moscona, A.Rotation-mediated histogenetic aggregation of dissociated cells. A quantifiable approach to cell interactions in vitro. Exp Cell Res,(1961); 22: p. 455-75.
Bing, R.J., T. Binder, J. Pataricza, et al.The use of microcarrier beads in the production of endothelium-derived relaxing factor by freshly harvested endothelial cells. Tissue Cell,(1991); 23(2): p. 151-9.
Nagaki, M., T. Kano, Y. Muto, et al.Effects of intraperitoneal transplantation of microcarrier-attached hepatocytes on D-galactosamine-induced acute liver failure in rats. Gastroenterol Jpn,(1990); 25(1): p. 78-87.
Shankar, R. and J.D. Sallis.Phosphocitrate inhibition of 45Ca2+ uptake in rat aortic smooth muscle cells in primary culture. Biochem Biophys Res Commun,(1985); 131(2): p. 793-9.
Davies, P.F. and C. Kerr.Co-Cultivation of Vascular Endothelial and Smooth-Muscle Cells Using Microcarrier Techniques. Experimental Cell Research,(1982); 141(2): p. 455-459.
Bell, E.Strategy for the selection of scaffolds for tissue engineering. Tissue Eng,(1995); 1(2): p. 163-79.
Martin, I., R.F. Padera, G. Vunjak-Novakovic, et al.In vitro differentiation of chick embryo bone marrow stromal cells into cartilaginous and bone-like tissues. J Orthop Res,(1998); 16(2): p. 181-9.
Tan, W., R. Krishnaraj and T.A. Desai.Evaluation of nanostructured composite collagen--chitosan matrices for tissue engineering. Tissue Eng,(2001); 7(2): p. 203-10.
