Abstract
Purpose
Three dimensional (3D) “in vitro” models are progressively being applied to investigate tumor cell biology and the interaction of cancer cells with tumor microenvironment under conditions more similar and realistic to “in vivo” behavior than standard bidimensional (2D) cultures.
Methods
In the last years, different methods have been developed to create spheroids and organoids and each technique has advantages and limitations also based on individual needs and cell types used. This review offers an overview of methodologies used for 3D systems: scaffold-free and scaffold-based methods up to bioreactors and organ-on-chip models.
Results
The principal goal for researchers is to select the 3D system that best suits their needs and that reflects the tumor model they want to study. A large chapter is dedicated to the application of these models to lymphomas’ study, a neoplasm still little explored in the 3D field.
Conclusion
These innovative and advanced models may represent new tools for cancer research and pre-clinical studies of new therapies in the perspective of precision medicine.
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Code availability
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Change history
17 May 2022
A Correction to this paper has been published: https://doi.org/10.1007/s00432-022-04052-8
References
Ahmed EM (2015) Hydrogel: preparation, characterization, and applications: a review. J Adv Res 6(2):105–121. https://doi.org/10.1016/j.jare.2013.07.006
Andersen T, Auk-Emblem P, Dornish M (2015) 3D cell culture in alginate hydrogels. Microarrays 4:133–161. https://doi.org/10.3390/microarrays4020133
Apoorva FNU, Tian YF, Pierpont TM, Bassen DM, Cerchietti L, Butcher JT, Weiss RS, Singh A (2017) Award winner in the young investigator category, 2017 society for biomaterials annual meeting and exposition, Minneapolis, MN, April 05–08, 2017: lymph node stiffness-mimicking hydrogels regulate human B-cell lymphoma growth and cell surface receptor expression in a molecular subtype-specific manner. J Biomed Mater Res 105(7):1833–1844. https://doi.org/10.1002/jbm.a.36031
Axpe E, Oyen ML (2016) Applications of alginate-based bioinks in 3D bioprinting. Int J Mol Sci 17(12):1976. https://doi.org/10.3390/ijms17121976
Baker BM, Chen CS (2012) Deconstructing the third dimension—how 3D culture microenvironments alter cellular cues. J Cell Sci 125(Pt 13):3015–3024. https://doi.org/10.1242/jcs.079509
Birgersdotter A, Baumforth KR, Porwit A, Sundblad A, Falk KI, Wei W, Sjöberg J, Murray PG, Björkholm M, Ernberg I (2007) Three-dimensional culturing of the Hodgkin lymphoma cell-line L1236 induces a HL tissue-like gene expression pattern. Leuk Lymphoma 48(10):2042–2053. https://doi.org/10.1080/10428190701573190
Breslin S, O’Driscoll L (2013) Three-dimensional cell-culture: the missing link in drug discovery. Drug Discov Today 18(5–6):240–249. https://doi.org/10.1016/j.drudis.2012.10.003
Caicedo-Carvajal CE, Liu Q, Remache Y, Goy A, Suh KS (2011) Cancer tissue engineering: a novel 3D polystyrene scaffold for in vitro isolation and amplification of lymphoma cancer cells from heterogeneous cell mixtures. J Tissue Eng 2011:362326. https://doi.org/10.4061/2011/362326
Caicedo-Carvajal CE, Liu Q, Goy A, Pecora A, Suh KS (2012) Three-dimensional cell culture models for biomarker discoveries and cancer research. Transl Med S1. https://doi.org/10.4172/2161-1025.S1-005
Candini O, Grisendi G, Foppiani EM, Brogli M, Aramini B, Masciale V, Spano C, Petracchi T, Veronesi E, Conte P et al (2019) A novel 3D in vitro platform for pre-clinical investigations in drug testing, gene therapy, and immuno-oncology. Sci Rep 9(1):7154. https://doi.org/10.1038/s41598-020-57846-6
Cayrol F, Diaz Flaque MC, Fernando T, Yang SN, Sterle HA, Bolontrade M, Amoros M, Isse B, Farias RN et al (2015) Integrin alphavbeta3 acting as membrane receptor for thyroid hormones mediates angiogenesis in malignant T cells. Blood 125:841–851. https://doi.org/10.1182/blood-2014-07-587337
Chaudhuri O, Koshy ST, Branco da Cunha C, Shin JW, Verbeke CS, Allison KH, Mooney DJ (2014) Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. Nat Mater 13:970–978. https://doi.org/10.1038/nmat4009
Chitcholtan K, Asselin E, Parent S, Sykes PH, Evans JJ (2013) Differences in growth properties of endometrial cancer in three dimensional (3D) culture and 2D cell monolayer. Exp Cell Res 319:75–87. https://doi.org/10.1016/j.yexcr.2012.09.012
Clevers H (2016) Modeling development and disease with organoids. Cell 165(7):1586–1597. https://doi.org/10.1016/j.cell.2016.05.082
Cui X, Hartanto Y, Zhang H (2017) Advances in multicellular spheroids formation. J R Soc Interface 14(127):20160877. https://doi.org/10.1098/rsif.2016.0877
Decaup E, Jean C, Laurent C, Gravelle P, Fruchon S, Capilla F, Marrot A, Al Saati T, Frenois FX, Laurent G et al (2013) Anti-tumor activity of obinutuzumab and rituximab in a follicular lymphoma 3D model. Blood Cancer J 3(8):e131. https://doi.org/10.1038/bcj.2013.32
Decaup E, Rossi C, Gravelle P, Laurent C, Bordenave J, Tosolini M, Tourette A, Perrial E, Dumontet C, Poupot M et al (2019) A tridimensional model for NK cell-mediated ADCC of follicular lymphoma. Front Immunol 10:1943. https://doi.org/10.3389/fimmu.2019.01943
Edmonson R, Broglie JJ, Adcock AF, Yang L (2014) Three-dimensional cell culture system and their applications in drug discovery and cell-based biosensors. Assay Drug Dev Technol 12(4):207–218. https://doi.org/10.1089/adt.2014.573
Eng C (2008) Microenvironmental protection in diffuse large-B-cell lymphoma. N Engl J Med 359(22):2379–2381. https://doi.org/10.1056/NEJMe0808409
Fan H, Demirci U, Chen P (2019) Emerging organoid models: leaping forward in cancer research. J Hematol Oncol 12(1):142. https://doi.org/10.1186/s13045-019-0832-4
Foxall R, Narang P, Glaysher B, Hub E, Teal E, Coles MC, Ashton-Key M, Beers SA, Cragg MS (2021) Developing a 3D B cell lymphoma culture system to model antibody therapy. Front Immunol 11:605231. https://doi.org/10.3389/fimmu.2020.605231
Gava F, Faria C, Gravelle P, Valero JG, Dobaño-López C, Morin R, Norlund M, Gomes A, Lagarde JM, Rossi C et al (2021) 3D model characterization by 2D and 3D imaging in t(14;18)-positive B-NHL: perspectives for in vitro drug screens in follicular lymphoma. Cancers (basel) 13(7):1490. https://doi.org/10.3390/cancers13071490
Gravelle P, Jean C, Valleron W, Laurent G, Fournié JJ (2012) Innate predisposition to immune escape in follicular lymphoma cells. Oncoimmunology 1(4):555–556. https://doi.org/10.4161/onci.19365
Gravelle P, Jean C, Familiades J, Decaup E, Blanc A, Bezombes-Cagnac C, Laurent C, Savina A, Fournié JJ, Laurent G (2014) Cell growth in aggregates determines gene expression, proliferation, survival, chemoresistance, and sensitivity to immune effectors in follicular lymphoma. Am J Pathol 184(1):282–295. https://doi.org/10.1016/j.ajpath.2013.09.018
Hirschhaeuser F, Menne H, Dittfeld C, West J, Mueller-Klieser W, Kunz-Schughart LA (2010) Multicellular tumor spheroids: an underestimated tool is catching up again. J Biotechnol 148(1):3–15. https://doi.org/10.1016/j.jbiotec.2010.01.012
Hirt C, Papadimitropoulos A, Mele V, Muraro MG, Mengus C, Iezzi G, Terracciano L, Martin I, Spagnoli GC (2014) “In vitro” 3D models of tumor-immune system interaction. Adv Drug Deliv Rev 79–80:145–154. https://doi.org/10.1016/j.addr.2014.05.003
Hongisto V, Jernström S, Fey V, Mpindi JP, Kleivi Sahlberg K, Kallioniemi O, Perälä M (2013) High-throughput 3D screening reveals differences in drug sensitivities between culture models of JIMT1 breast cancer cells. PLoS ONE 8:e77232. https://doi.org/10.1371/journal.pone.0077232
Hua H, Li M, Luo T, Yin Y, Jiang Y (2011) Matrix metalloproteinases in tumorigenesis: an evolving paradigm. Cell Mol Life Sci 68(23):3853–3868. https://doi.org/10.1007/s00018-011-0763-x
Hughes P, Marshall D, Reid Y, Parkes H, Gelber C (2007) The costs of using unauthenticated, over-passaged cell lines: how much more data do we need? Biotechniques 43(5):575, 577–578, 581–582 passim. https://doi.org/10.2144/000112598
Huh D, Fujioka H, Tung YC, Futai N, Paine R 3rd, Grotberg JB, Takayama S (2007) Acoustically detectable cellular-level lung injury induced by fluid mechanical stresses in microfluidic airway systems. Proc Natl Acad Sci USA 104:18886–18891. https://doi.org/10.1073/pnas.0610868104
Ikram M, Lim Y, Baek SY, Jin S, Jeong YH, Kwak JY, Yoon S (2017) Co-targeting of Tiam1/Rac1 and notch ameliorates chemoresistance against doxorubicin in a biomimetic 3D lymphoma model. Oncotarget 9(2):2058–2075. https://doi.org/10.18632/oncotarget.23156
Jacks T, Weinberg RA (2002) Taking the study of cancer cell survival to a new dimension. Cell 111(7):923–925. https://doi.org/10.1016/s0092-8674(02)01229-1
Jackson EL, Lu H (2016) Three-dimensional models for studying development and disease: moving on from organisms to organs-on-a-chip and organoids. Integr Biol (camb) 8(6):672–683. https://doi.org/10.1039/c6ib00039h
Jang KJ, Suh KY (2010) A multi-layer microfluidic device for efficient culture and analysis of renal tubular cells. Lab Chip 10:36–42. https://doi.org/10.1039/b907515a
Jean-Quartier C, Jeanquartier F, Jurisica I, Holzinger A (2018) In silico cancer research towards 3R. BMC Cancer 18(1):408. https://doi.org/10.1186/s12885-018-4302-0
Jørgensen A, Young J, Nielsen JE, Joensen UN, Toft BG, Rajpert-De Meyts E, Loveland KL (2014) Hanging drop cultures of human testis and testis cancer samples: a model used to investigate activin treatment effects in a preserved niche. Br J Cancer 110(10):2604–2614. https://doi.org/10.1038/bjc.2014.160
Kelm JM, Timmins NE, Brown CJ, Fussenegger M, Nielsen LK (2003) Method for generation of homogeneous multicellular tumor spheroids applicable to a wide variety of cell types. Biotechnol Bioeng 83:173–180. https://doi.org/10.1002/bit.10655
Kenny PA, Lee GY, Neve RM, Semeikis JR, Spellman PT, Lorenz K, Lee EH, Barcellos-Hoff MH, Petersen OW, Gray JW, Bissell MJ (2007) The morphologies of breast cancer cell lines in three-dimensional assays correlate with their profiles of gene expression. Version 2. Mol Oncol 1(1):84–96. https://doi.org/10.1016/j.molonc.2007.02.004
Kim HJ, Huh D, Hamilton G, Ingber DE (2012) Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12(12):2165–2174. https://doi.org/10.1039/c2lc40074j
Kiss DL, Windus LC, Avery VM (2013) Chemokine receptor expression on integrin-mediated stellate projection of prostate cancer cells in 3D culture. Cytokine 64(1):122–130. https://doi.org/10.1016/j.cyto.2013.07.012
Knight E, Przyborski S (2015) Advances in 3D cell culture technologies enabling tissue-like structures to be created in vitro. J Anat 227(6):746–756. https://doi.org/10.1111/joa.12257
Kunz-Schughart LA, Kreutz M, Knuechel R (1998) Multicellular spheroids: a three dimensional in vitro culture system to study tumour biology. Int J Exp Pathol 79(1):1–23. https://doi.org/10.1046/j.1365-2613.1998.00051.x
Lancaster MA, Knoblich JA (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345(6194):1247125. https://doi.org/10.1126/science.1247125
Langhans SA (2018) Three-dimensional in vitro cell culture models in drug discovery and drug repositioning. Front Pharmacol 9:6. https://doi.org/10.3389/fphar.2018.00006
Lee GY, Kenny PA, Lee EH, Bissell MJ (2007a) Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Protoc 4:359–365. https://doi.org/10.1038/nmeth1015
Lee PJ, Hung PJ, Lee LP (2007b) An artificial liver sinusoid with a microfluidic endothelial-like barrier for primary hepatocyte culture. Biotechnol Bioeng 97:1340–1346. https://doi.org/10.1002/bit.21360
Lee GY, Kenny PA, Lee EH, Bissell MJ (2007c) Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods 4(4):359–365 (in Eng [PubMed: 17396127])
Lee TT, García JR, Paez JI, Singh A, Phelps EA, Weis S, Shafiq Z, Shekaran A, Del Campo A, García AJ (2015) Light-triggered in vivo activation of adhesive peptides regulates cell adhesion, inflammation and vascularization of biomaterials. Nat Mater 14(3):352–360. https://doi.org/10.1038/nmat4157
Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J et al (2008) Stromal gene signatures in large-B-cell lymphomas. N Engl J Med 359(22):2313–2323. https://doi.org/10.1056/NEJMoa0802885
Leonard F, Godin B (2016) 3D In vitro model for breast cancer research using magnetic levitation and bioprinting method. Methods Mol Biol 1406:239–251. https://doi.org/10.1007/978-1-4939-3444-7_21
Lin RZ, Chang HY (2008) Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol J3(9–10):1172–1184. https://doi.org/10.1002/biot.200700228
Loessner D, Stok KS, Lutolf MP, Hutmacher DW, Clements JA, Rizzi SC (2010) Bioengineered 3D platform to explore cell-ECM interactions and drug resistance of epithelial ovarian cancer cells. Biomaterials 31(32):8494–8506. https://doi.org/10.1016/j.biomaterials.2010.07.064
Luca AC, Mersch S, Deenen R, Schmidt S, Messner I, Schäfer KL, Baldus SE, Huckenbeck W, Piekorz RP, Knoefel WT et al (2013) Impact of the 3D microenvironment on phenotype, gene expression, and EGFR inhibition of colorectal cancer cell lines. PLoS ONE 8(3):e59689. https://doi.org/10.1371/journal.pone.0059689
Ludwig K, Tse ES, Wang JY (2013) Colon cancer cells adopt an invasive phenotype without mesenchymal transition in 3-D but not 2-D culture upon combined stimulation with EGF and crypt growth factors. BMC Cancer 13:221. https://doi.org/10.1186/1471-2407-13-221
Ma PX, Choi JW (2001) Biodegradable polymer scaffolds with well-defined interconnected spherical pore network. Tissue Eng 7(1):23–33. https://doi.org/10.1089/107632701300003269
Mannino RG, Pradhan P, Roy K, Lam WA (2017) 3D microvascular model recapitulates the diffuse large B-cell lymphoma tumor microenvironment in vitro. Lab Chip 17(3):407–414. https://doi.org/10.1039/c6lc01204c
Marsee A, Roos FJM, Verstegen MMA, Gehart H, de Koning E, Lemaigre F, Forbes SJ, Peng WC, Huch M et al (2021) Building consensus on definition and nomenclature of hepatic, pancreatic, and biliary organoids. Cell Stem Cell 28(5):816–832. https://doi.org/10.1016/j.stem.2021.04.005
Mironi-Harpaz I, Berdichevski A, Seliktar D (2014) Fabrication of PEGylated fibrinogen: a versatile injectable hydrogel biomaterial. Methods Mol Biol 1181:61–68. https://doi.org/10.1007/978-1-4939-1047-2_6
Naci D, El Azreq MA, Chetoui N, Lauden L, Sigaux F, Charron D, Al-Daccak R, Aoudjit F (2012) Alpha2beta1 integrin promotes chemoresistance against doxorubicin in cancer cells through extracellular signal-regulated kinase (ERK). J Biol Chem 287(21):17065–17076. https://doi.org/10.1074/jbc.M112.349365
Nath S, Devi GR (2016) Three-dimensional culture systems in cancer research: focus on tumor spheroid model. Pharmacol Ther 163:94–108. https://doi.org/10.1016/j.pharmthera.2016.03.013
Nguyen K, West J (2002) Photopolymerizable hydrogels for tissue engineering applications. Biomaterials 23:4307–4314. https://doi.org/10.1016/s0142-9612(02)00175-8
Nisbet DR, Forsythe JS, Shen W, Finkelstein DI, Horne MK (2009) Review paper: a review of the cellular response on electrospun nanofibers fortissue engineering. J Biomater Appl 24(1):7–29. https://doi.org/10.1177/0885328208099086
Purwada A, Singh A (2017) Immuno-engineered organoids for regulating the kinetics of B cell development and antibody production. Nat Protoc 12:168–182. https://doi.org/10.1038/nprot.2016.157
Purwada A, Jaiswal MK, Ahn H, Nojima T, Kitamura D, Gaharwar AK, Cerchietti L, Singh A (2015) Ex vivo engineered immune organoids for controlled germinal center reactions. Biomaterials 63:24–34. https://doi.org/10.1016/j.biomaterials.2015.06.002
Ranga A, Gjorevski N, Lutolf MP (2014) Drug discovery through stem cell-based organoid models. Adv Drug Deliv Rev 69–70:19–28. https://doi.org/10.1016/j.addr.2014.02.006
Riedl A, Schlederer M, Pudelko K, Stadler M, Walter S, Unterleuthner D, Unger C, Kramer N, Hengstschläger M, Kenner L et al (2017) Comparison of cancer cells in 2D vs 3D culture reveals differences in AKT-mTOR-S6K signaling and drug responses. J Cell Sci 1:203–218. https://doi.org/10.1242/jcs.188102
Rossi C, Gravelle P, Decaup E, Bordenave J, Poupot M, Tosolini M, Franchini DM, Laurent C, Morin R, Lagarde JM et al (2018) Boosting γδ T cell-mediated antibody-dependent cellular cytotoxicity by PD-1 blockade in follicular lymphoma. Oncoimmunology 8(3):1554175. https://doi.org/10.1080/2162402X.2018.1554175
Sabhachandani P, Sarkar S, Mckenney S, Ravi D, Evens AM, Konry T (2019) Microfluidic assembly of hydrogel-based immunogenic tumor spheroids for evaluation of anticancer therapies and biomarker release. J Control Release 295:21–30. https://doi.org/10.1016/j.jconrel.2018.12.010
Scott DW, Gascoyne RD (2014) The tumour microenvironment in B cell lymphomas. Nat Rev Cancer 14(8):517–534. https://doi.org/10.1038/nrc3774
Shamir ER, Eald AJ (2014) Three-dimensional organotypic culture: experimental models of mammalian biology and disease. Nat Rev Mol Cell Biol 15(10):647–664. https://doi.org/10.1038/nrm3873
Singh RR, Kunkalla K, Qu C, Schlette E, Neelapu SS, Samaniego F, Vega F (2011) ABCG2 is a direct transcriptional target of hedgehog signaling and involved in stroma-induced drug tolerance in diffuse large B-cell lymphoma. Oncogene 30(49):4874–4886. https://doi.org/10.1038/onc.2011.195
Singh M, Close DA, Mukundan S (2015) Production of uniform 3D microtumors in hydrogel microwell arrays for measurement of viability, morphology, and signaling pathway activation. Assay Drug Dev Technol 13(9):570–583. https://doi.org/10.1089/adt.2015.662
Sneddon LU, Halsey LG, Bury NR (2017) Considering aspects of the 3rs principles within experimental animal biology. J Exp Biol 220(17):3007–3016. https://doi.org/10.1242/jeb.147058
Sutherland RM (1988) Cell and environment interactions in tumor microregions: the multicell spheroid model. Science 240(4849):177–184. https://doi.org/10.1126/science.2451290
Sutherland RM, McCredie JA, Inch WR (1971) Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. J Natl Cancer Inst 46(1):113–120
Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (2017) WHO classification of tumors of haematopoietic and lymphoid tissues. WHO classification of tumours, revised, vol 2, 4th edn. IARC, Lyon
Tian YF, Ahn H, Schneider RS, Yang SN, Roman-Gonzalez L, Melnick AM, Cerchietti L, Singh A (2015) Integrin-specific hydrogels as adaptable tumor organoids for malignant B and T cells. Biomaterials 73:110–119. https://doi.org/10.1016/j.biomaterials.2015.09.007
Tibbitt MW, Anseth KS (2009) Hydrogels as extracellular matrix mimics for 3D cell culture. Biotechnol Bioeng 103(4):655–663. https://doi.org/10.1002/bit.22361
Timmins NE, Nielsen LK (2007) Generation of multicellular tumor spheroids by the hanging-drop method. Methods Mol Med 140:141–151. https://doi.org/10.1007/978-1-59745-443-8_8
Torisawa YS, Spina CS, Mammoto T, Mammoto A, Weaver JC, Tat T, Collins JJ, Ingber DE (2014) Bone marrow-on-a-chip replicates hematopoietic niche physiology in vitro. Nat Methods 11(6):663–669. https://doi.org/10.1038/nmeth.2938
Tseng H, Gage JA, Shen T, Haisler WL, Neeley SK, Shiao S, Chen J, Desai PK, Liao A, Hebel C et al (2015) A spheroid toxicity assay using magnetic 3D bioprinting and real-time mobile device-based imaging. Sci Rep 5:13987. https://doi.org/10.1038/srep13987
Tung Y-C, Hsiao AY, Allen SG, Torisawa Y, Ho M, Takayama S (2011) High-throughput 3D spheroid culture and drug testing using a 384 hanging drop array. Analyst 136(3):473–478. https://doi.org/10.1039/c0an00609b
Vidal-Crespo A, Matas-Céspedes A, Rodriguez V, Rossi C, Valero JG, Serrat N, Sanjuan-Pla A, Menéndez P, Roué G, López-Guillermo A et al (2020) Daratumumab displays in vitro and in vivo anti-tumor activity in models of B cell non-Hodgkin lymphoma and improves responses to standard chemo-immunotherapy regimens. Haematologica 105(4):1032–1041. https://doi.org/10.3324/haematol.2018.211904
Vinci M, Gowan S, Boxall F, Patterson L, Zimmermann M, Court W, Lomas C, Mendiola M, Hardisson D, Sa E (2012) Advances in establishment and analysis of three-dimensional tumor spheroid-based functional assays for target validation and drug evaluation. BMC Biol 10:29. https://doi.org/10.1186/1741-7007-10-29
Weaver VM, Lelièvre S, Lakins JN, Chrenek MA, Jones JC, Giancotti F, Werb Z, Bissell MJ (2002) Beta4 integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell 2(3):205–216. https://doi.org/10.1016/s1535-6108(02)00125-3
Weiswald LB, Bellet D, Dangles-Marie V (2015) Spherical cancer models in tumor biology. Neoplasia 17(1):1–15. https://doi.org/10.1016/j.neo.2014.12.004
Yamada KM, Cukierman E (2007) Modeling tissue morphogenesis and cancer in 3D. Cell 130(4):601–610. https://doi.org/10.1016/j.cell.2007.08.006
Yin X, Mead BE, Safaee H, Langer R, Karp JM, Levy O (2016) Engineering stem cell organoids. Cell Stem Cell 18(1):25–38. https://doi.org/10.1016/j.stem.2015.12.005
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Rossi, M., Alviano, F., Righi, S. et al. Three-dimensional models: a novel approach for lymphoma research. J Cancer Res Clin Oncol 148, 753–765 (2022). https://doi.org/10.1007/s00432-021-03897-9
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DOI: https://doi.org/10.1007/s00432-021-03897-9