ÜÇ BOYUTLU HÜCRE KÜLTÜRÜ SİSTEMLERİNE GÜNCEL YAKLAŞIMLAR

İki boyutlu (2B) hücre kültürü, hücre temelli araştırmalar için değerli bir yöntemdir ancak in vivo yanıtlar hakkında öngörülemeyen, yanıltıcı veriler sağlayabilir. Son yirmi yılda, hücresel mikro çevrenin (örneğin hücre dışı matris ve interstisyel sıvı) önemine farkındalık artmıştır. Dolayısıyla, 3B hücre kültürü olarak adlandırılan bu yeni hücre kültürü paradigması hızla popülerlik kazanmaktadır. 2B kültürlerden 3B kültür tekniklerine geçiş ile birlikte fizyolojik olarak canlılardaki dokulara daha benzer olan modellerin ortaya çıkarılması sağlanmaktadır. 3B hücre kültürleri farklı amaçlar için faklı teknikler sunar ve gereksinime göre kullanıcıların en uygun modeli seçmeleri gerekir. 3B hücre kültürü sistemlerinin, kök hücre çalışmaları, ilaç keşifleri, kanser araştırmaları, gen ve protein ekspresyon çalışmalarının da içerisinde olduğu birçok karmaşık fizyolojik mekanizmanın aydınlatılmasında yaygınca kullanıldığı görülmektedir. Bu derlemenin amacı 2B kültürler ile 3B kültürleri karşılaştırarak mevcut 3B kültürlerin uygulama alanlarını tartışmaktır.

Current Approaches to Three-Dimensional Cell Culture System

Two-dimensional (2D) cell culture is a valuable method for cell-based research, However, it may provide unpredictable, misleading data on in vivo responses. Over the last two decades, awareness of the importance of the cellular microenvironment (e.g. extracellular matrix and interstitial fluid) has increased. This new cell culture paradigm, called as 3D cell culture, is rapidly gaining popularity. With the transition from 2D cultures to 3D culture techniques, it is provided the reveal of models that are more similar to living tissues physiologically. 3D cell cultures offer different techniques for different purposes, and users need to choose the most available model according to the requirement. 3D cell culture systems have been used to clarify the complex physiological mechanisms in the fields of stem cell studies, drug discoveries, cancer research, gene and protein expression studies. The aim of this review was to discuss the application areas of existing 3D cultures in comparison with 2D cultures and 3D cultures.

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1.Ravi M, Paramesh V, Kaviya S, Anuradha E, Solomon FP. 3D cell culture systems: advantages and applications. Journal of cellular physiology. 2015;230(1):16-26.
2. Knight E, Przyborski S. Advances in 3D cell culture technologies enabling tissue‐like structures to be created in vitro. Journal of anatomy. 2015;227(6):746-756.
3. Huh D, Hamilton GA, Ingber DE. From 3D cell culture to organs-on-chips. Trends in cell biology. 2011;21(12):745-754.
4. Duval K, Grover H, Han L-H, Mou Y, Pegoraro AF, Fredberg J, et al. Modeling physiological events in 2D vs. 3D cell culture. Physiology. 2017;32(4):266-277.
5. Burdick JA, Vunjak-Novakovic G. Engineered microenvironments for controlled stem cell differentiation. Tissue Engineering Part A. 2008;15(2):205-219.
6. Freshney R. Culture of Animal Cells: A Manual of Basic Technique: Wiley-Liss; 2005.
7. Edmondson R, Broglie JJ, Adcock AF, Yang L. Threedimensional cell culture systems and their applications in drug discovery and cell-based biosensors. Assay and drug development technologies. 2014;12(4):207-218.
8. Choi SW, Yeh YC, Zhang Y, Sung HW, Xia Y. Uniform beads with controllable pore sizes for biomedical applications. Small. 2010;6(14):1492-1498.
9. Vinci M, Gowan S, Boxall F, Patterson L, Zimmermann M, Lomas C, et al. Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation. BMC biology. 2012;10(1):29.
10. Weaver VM, Petersen OW, Wang F, Larabell C, Briand P, Damsky C, et al. Reversion of the malignant phenotype of human breast cells in three-dimensional culture and in vivo by integrin blocking antibodies. The Journal of cell biology. 1997;137(1):231-245.
11. Lin CQ, Bissell MJ. Multi-faceted regulation of cell differentiation by extracellular matrix. The FASEB Journal. 1993;7(9):737-743.
12. Bonnier F, Keating M, Wrobel TP, Majzner K, Baranska M, Garcia-Munoz A, et al. Cell viability assessment using the Alamar blue assay: a comparison of 2D and 3D cell culture models. Toxicology in vitro. 2015;29(1):124-131.
13. Chitcholtan K, Asselin E, Parent S, Sykes PH, Evans JJ. Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer. Experimental cell research. 2013;319(1):75-87.
14. Mabry KM, Payne SZ, Anseth KS. Microarray analyses to quantify advantages of 2D and 3D hydrogel culture systems in maintaining the native valvular interstitial cell phenotype. Biomaterials. 2016;74:31-41.
15. Pineda ET, Nerem RM, Ahsan T. Differentiation patterns of embryonic stem cells in two-versus three-dimensional culture. Cells Tissues Organs. 2013;197(5):399-410.
16. Ji C, Khademhosseini A, Dehghani F. Enhancing cell penetration and proliferation in chitosan hydrogels for tissue engineering applications. Biomaterials. 2011;32(36):9719-9729.
17. Kimlin LC, Casagrande G, Virador VM. In vitro three‐dimensional (3D) models in cancer research: an update. Molecular carcinogenesis. 2013;52(3):167-182.
18. Bott K, Upton Z, Schrobback K, Ehrbar M, Hubbell JA, Lutolf MP, et al. The effect of matrix characteristics on fibroblast proliferation in 3D gels. Biomaterials. 2010;31(32):8454-8464.
19. Grinnell F. Fibroblast biology in three-dimensional collagen matrices. Trends in cell biology. 2003;13(5):264-269.
20. Hakkinen KM, Harunaga JS, Doyle AD, Yamada KM. Direct comparisons of the morphology, migration, cell adhesions, and actin cytoskeleton of fibroblasts in four different three-dimensional extracellular matrices. Tissue Engineering Part A. 2010;17(5-6):713-724.
21. Wang F, Weaver VM, Petersen OW, Larabell CA, Dedhar S, Briand P, et al. Reciprocal interactions between β1-integrin and epidermal growth factor receptor in three-dimensional basement membrane breast cultures: a different perspective in epithelial biology. Proceedings of the National Academy of Sciences. 1998;95(25):14821-14826.
22. Koch TM, Münster S, Bonakdar N, Butler JP, Fabry B. 3D traction forces in cancer cell invasion. PloS one. 2012;7(3):e33476.
23. Steinwachs J, Metzner C, Skodzek K, Lang N, Thievessen I, Mark C, et al. Three-dimensional force microscopy of cells in biopolymer networks. Nature methods. 2016;13(2):171.
24. Wang K, Cai L-H, Lan B, Fredberg JJ. Hidden in the mist no more: physical force in cell biology. Nature methods. 2016;13(2):124.
25. Langer R, Tirrell DA. Designing materials for biology and medicine. Nature. 2004;428(6982):487-492.
26. Lin RZ, Chang HY. Recent advances in three‐dimensional multicellular spheroid culture for biomedical research. Biotechnology Journal: Healthcare Nutrition Technology. 2008;3(9‐10):1172-1184.
27. Rivron NC, Raiss CC, Liu J, Nandakumar A, Sticht C, Gretz N, et al. Sonic Hedgehog-activated engineered blood vessels enhance bone tissue formation. Proceedings of the National Academy of Sciences. 2012;109(12):4413-4418.
28. Fennema E, Rivron N, Rouwkema J, van Blitterswijk C, de Boer J. Spheroid culture as a tool for creating 3D complex tissues. Trends in biotechnology. 2013;31(2):108-115.
29. Harrison RG, Greenman M, Mall FP, Jackson C. Observations of the living developing nerve fiber. The Anatomical Record. 1907;1(5):116-128.
30. van Duinen V, Trietsch SJ, Joore J, Vulto P, Hankemeier T. Microfluidic 3D cell culture: from tools to tissue models. Current opinion in biotechnology. 2015;35:118- 126.
31. Yuhas JM, Li AP, Martinez AO, Ladman AJ. A simplified method for production and growth of multicellular tumor spheroids. Cancer research. 1977;37(10):3639-3643.
32. Handschel JG, Depprich RA, Kübler NR, Wiesmann HP, Ommerborn M, Meyer U. Prospects of micromass culture technology in tissue engineering. Head & face medicine. 2007;3(1):4.
33. Napolitano AP, Chai P, Dean DM, Morgan JR. Dynamics of the self-assembly of complex cellular aggregates on micromolded nonadhesive hydrogels. Tissue engineering. 2007;13(8):2087-2094.
34. Torisawa Y-s, Chueh B-h, Huh D, Ramamurthy P, Roth TM, Barald KF, et al. Efficient formation of uniform-sized embryoid bodies using a compartmentalized microchannel device. Lab on a Chip. 2007;7(6):770-776.
35. Moroni L, De Wijn J, Van Blitterswijk C. Integrating novel technologies to fabricate smart scaffolds. Journal of Biomaterials Science, Polymer Edition. 2008;19(5):543- 572.
36. Gu BK, Choi DJ, Park SJ, Kim Y-J, Kim C-H. 3D bioprinting technologies for tissue engineering applications. Cutting-Edge Enabling Technologies for Regenerative Medicine: Springer; 2018:15-28.
37. Chaicharoenaudomrung N, Kunhorm P, Noisa P. Threedimensional cell culture systems as an in vitro platform for cancer and stem cell modeling. World Journal of Stem Cells. 2019;11(12):1065.
38. Chung BG, Lee K-H, Khademhosseini A, Lee S-H. Microfluidic fabrication of microengineered hydrogels and their application in tissue engineering. Lab on a Chip. 2012;12(1):45-59.
39. Ruedinger F, Lavrentieva A, Blume C, Pepelanova I, Scheper T. Hydrogels for 3D mammalian cell culture: a starting guide for laboratory practice. Applied microbiology and biotechnology. 2015;99(2):623-636.
40. Whitesides GM. The origins and the future of microfluidics. Nature. 2006;442(7101):368.
41. Gogoi P, Sepehri S, Zhou Y, Gorin MA, Paolillo C, Capoluongo E, et al. Development of an automated and sensitive microfluidic device for capturing and characterizing circulating tumor cells (CTCs) from clinical blood samples. PloS one. 2016;11(1):e0147400.
42. Yeatts AB, Choquette DT, Fisher JP. Bioreactors to influence stem cell fate: augmentation of mesenchymal stem cell signaling pathways via dynamic culture systems. Biochimica et Biophysica Acta (BBA)-General Subjects. 2013;1830(2):2470-2480.
43. Andersen T, Auk-Emblem P, Dornish M. 3D cell culture in alginate hydrogels. Microarrays. 2015;4(2):133-161.
44. Murphy SV, Atala A. 3D bioprinting of tissues and organs. Nature biotechnology. 2014;32(8):773.
45. Tasoglu S, Demirci U. Bioprinting for stem cell research. Trends in biotechnology. 2013;31(1):10-19.
46. Knowlton S, Onal S, Yu CH, Zhao JJ, Tasoglu S. Bioprinting for cancer research. Trends in biotechnology. 2015;33(9):504-513.
47. Gurski LA, Petrelli NJ, Jia X, Farach-Carson MC. 3D matrices for anti-cancer drug testing and development. Oncology Issues. 2010;25(1):20-25.
48. Zheng Y, Chen J, Craven M, Choi NW, Totorica S, DiazSantana A, et al. In vitro microvessels for the study of angiogenesis and thrombosis. Proceedings of the national academy of sciences. 2012;109(24):9342-9347.
49. Swartz MA, Lund AW. Lymphatic and interstitial flow in the tumour microenvironment: linking mechanobiology with immunity. Nature Reviews Cancer. 2012;12(3):210- 219.
50. Munson JM, Bellamkonda RV, Swartz MA. Interstitial flow in a 3D microenvironment increases glioma invasion by a CXCR4-dependent mechanism. Cancer research. 2013;73(5):1536-1546.
51. Ma L, Zhang B, Zhou C, Li Y, Li B, Yu M, et al. The comparison genomics analysis with glioblastoma multiforme (GBM) cells under 3D and 2D cell culture conditions. Colloids and Surfaces B: Biointerfaces. 2018;172:665-673.
52. Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. British journal of pharmacology. 2011;162(6):1239-1249.
53. Tanner K, Gottesman MM. Beyond 3D culture models of cancer. Science translational medicine. 2015;7(283):283ps289-283ps289.
54. Imamura Y, Mukohara T, Shimono Y, Funakoshi Y, Chayahara N, Toyoda M, et al. Comparison of 2D-and 3D-culture models as drug-testing platforms in breast cancer. Oncology reports. 2015;33(4):1837-1843.
55. Pampaloni F, Stelzer EH, Masotti A. Three-dimensional tissue models for drug discovery and toxicology. Recent patents on biotechnology. 2009;3(2):103-117.
56. Lin Z, Will Y. Evaluation of drugs with specific organ toxicities in organ-specific cell lines. Toxicological Sciences. 2011;126(1):114-127.
57. Koehler KR, Mikosz AM, Molosh AI, Patel D, Hashino E. Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature. 2013;500(7461):217.
58. Luo Y, Lou C, Zhang S, Zhu Z, Xing Q, Wang P, et al. Three-dimensional hydrogel culture conditions promote the differentiation of human induced pluripotent stem cells into hepatocytes. Cytotherapy. 2018;20(1):95-107.
59. Farrell E, Byrne E, Fischer J, O'brien F, O'connell B, Prendergast P, et al. A comparison of the osteogenic potential of adult rat mesenchymal stem cells cultured in 2-D and on 3-D collagen glycosaminoglycan scaffolds. Technology and Health Care. 2007;15(1):19-31.
60. Erickson IE, Huang AH, Chung C, Li RT, Burdick JA, Mauck RL. Differential maturation and structure–function relationships in mesenchymal stem cell-and chondrocyte-seeded hydrogels. Tissue Engineering Part A. 2008;15(5):1041-1052.