Formation of Lymphoma Hybrid Spheroids and Drug Testing in Real Time with the Use of Fluorescence Optical Tweezers
Abstract
:1. Introduction
2. Materials and Methods
2.1. Optical Tweezers with Fluorescence Detection
2.2. Cell Lines and Culture Conditions
2.3. Preparation of Gels and Mesenchymal Stromal Spheroids
2.4. Formation of Multicellular Hybrid Spheroids in Optical Tweezers
2.5. Hybrid Spheroid Viability by Fluorescence Microscopy
2.6. Evaluation of the Adhesive Properties of Lymphoma Cells
2.7. Drugs and Treatment
2.8. Statistical Tests
3. Results
3.1. The Recapitulation of the 3D Hybrid Spheroid in Real Time in Optical Tweezers
3.2. The Stability and the Viability of the De Novo Formed Spheroid
3.3. The Assessment of the Adhesive Properties of Aggressive Lymphoma Cell Lines
3.4. The Influence of Combined Drug Treatment on Single-Cell Adhesion
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Swerdlow, S.H.; Campo, E.; Pileri, S.A.; Harris, N.L.; Stein, H.; Siebert, R.; Advani, R.; Ghielmini, M.; Salles, G.A.; Zelenetz, A.D.; et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016, 127, 2375–2390. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Conlan, M.G.; Bast, M.; Armitage, J.O.; Weisenburger, D.D. Bone marrow involvement by non-Hodgkin’s lymphoma: The clinical significance of morphologic discordance between the lymph node and bone marrow. Nebraska Lymphoma Study Group. J. Clin. Oncol. 1990, 8, 1163–1172. [Google Scholar] [CrossRef] [PubMed]
- Sehn, L.H.; Salles, G. DiffuseLarge B-Cell Lymphoma. N. Engl. J. Med. 2021, 384, 842–858. [Google Scholar] [CrossRef] [PubMed]
- Mourcin, F.; Pangault, C.; Amin-Ali, R.; Amé-Thomas, P.; Tarte, K. Stromal cell contribution to human follicular lymphoma pathogenesis. Front. Immunol. 2012, 3, 280. [Google Scholar] [CrossRef] [Green Version]
- Blonska, M.; Agarwal, N.K.; Vega, F. Shaping of the tumor microenvironment: Stromal cells and vessels. Semin. Cancer Biol. 2015, 34, 3–13. [Google Scholar] [CrossRef]
- Lwin, T.; Hazlehurst, L.A.; Li, Z.; Dessureault, S.; Sotomayor, E.; Moscinski, L.C.; Dalton, W.S.; Tao, J. Bone marrow stromal cells prevent apoptosis of lymphoma cells by upregulation of anti-apoptotic proteins associated with activation of NF-kappaB (RelB/p52) in non-Hodgkin’s lymphoma cells. Leukemia 2007, 21, 1521–1531. [Google Scholar] [CrossRef] [Green Version]
- Duś-Szachniewicz, K.; Drobczyński, S.; Ziółkowski, P.; Kołodziej, P.; Walaszek, K.M.; Korzeniewska, A.K.; Agrawal, A.; Kupczyk, P.; Woźniak, M. Physiological Hypoxia (Physioxia) Impairs the Early Adhesion of Single Lymphoma Cell to Marrow Stromal Cell and Extracellular Matrix. Optical Tweezers Study. Int. J. Mol. Sci. 2018, 19, 1880. [Google Scholar] [CrossRef] [Green Version]
- Duś-Szachniewicz, K.; Drobczyński, S.; Woźniak, M.; Zduniak, K.; Ostasiewicz, K.; Ziółkowski, P.; Korzeniewska, A.K.; Agrawal, A.K.; Kołodziej, P.; Walaszek, K.; et al. Differentiation of single lymphoma primary cells and normal B-cells based on their adhesion to mesenchymal stromal cells in optical tweezers. Sci. Rep. 2019, 9, 9885. [Google Scholar] [CrossRef]
- Nunes, A.S.; Barros, A.S.; Costa, E.C.; Moreira, A.F.; Correia, I.J. 3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs. Biotechnol. Bioeng. 2019, 116, 206–226. [Google Scholar] [CrossRef] [Green Version]
- Bassi, G.; Grimaudo, M.A.; Panseri, S.; Montesi, M. Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity. Int. J. Mol. Sci. 2021, 22, 1195. [Google Scholar] [CrossRef]
- Amereh, M.; Edwards, R.; Akbari, M.; Nadler, B. In-Silico Modeling of Tumor Spheroid Formation and Growth. Micromachines 2021, 12, 749. [Google Scholar] [CrossRef]
- Wallace, D.I.; Guo, X. Properties of tumor spheroid growth exhibited by simple mathematical models. Front. Oncol 2013, 3, 51. [Google Scholar] [CrossRef] [Green Version]
- Weiswald, L.B.; Bellet, D.; Dangles-Marie, V. Spherical cancer models in tumor biology. Neoplasia 2015, 17, 1–15. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khawar, I.A.; Park, J.K.; Jung, E.S.; Lee, M.A.; Chang, S.; Kuh, H.J. Three Dimensional Mixed-Cell Spheroids Mimic Stroma-Mediated Chemoresistance and Invasive Migration in hepatocellular carcinoma. Neoplasia 2018, 20, 800–812. [Google Scholar] [CrossRef]
- Goers, L.; Freemont, P.; Polizzi, K.M. Co-culture systems and technologies: Taking synthetic biology to the next level. J. R. Soc. Interface 2014, 11, 20140065. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yakavets, I.; Francois, A.; Benoit, A.; Merlin, J.-L.; Bezdetnaya, L.; Vogin, G. Advanced co-culture 3D breast cancer model for investigation of fibrosis induced by external stimuli: Optimization study. Sci. Rep. 2020, 10, 21273. [Google Scholar] [CrossRef] [PubMed]
- Zoetemelk, M.; Rausch, M.; Colin, D.J.; Dormond, O.; Nowak-Sliwinska, P. Short-term 3D culturesystems of variouscomplexity for treatmentoptimization of colorectal carcinoma. Sci. Rep. 2019, 9, 7103. [Google Scholar] [CrossRef]
- Lazzari, G.; Nicolas, V.; Matsusaki, M.; Akashi, M.; Couvreur, P.; Mura, S. Multicellular spheroid based on a triple co-culture: A novel 3D model to mimic pancreatic tumor complexity. Acta Biomater. 2018, 78, 296–307. [Google Scholar] [CrossRef]
- Duś-Szachniewicz, K.; Gdesz-Birula, K.; Rymkiewicz, G. Development and Characterization of 3D Hybrid Spheroids for the Investigation of the Crosstalk Between B-cell non-Hodgkin lymphomas and Mesenchymal Stromal Cells. OncoTargets Ther. 2022, 15, 683–697. [Google Scholar] [CrossRef]
- Pulze, L.; Congiu, T.; Brevini, T.A.L.; Grimaldi, A.; Tettamanti, G.; D’Antona, P.; Baranzini, N.; Acquati, F.; Ferraro, F.; de Eguileor, M. MCF7 Spheroid Development: New Insight about Spatio/Temporal Arrangements of TNTs, Amyloid Fibrils, Cell Connections, and Cellular Bridges. Int. J. Mol. Sci. 2020, 21, 5400. [Google Scholar] [CrossRef]
- Glass, D.G.; McAlinden, N.; Millington, O.R.; Wright, A.J. A minimally invasive optical trapping system to understand cellular interactions at onset of an immune response. PLoS ONE 2017, 12, e0188581. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Drobczyński, S.; Duś-szachniewicz, K. Real-time force measurement in double wavelength optical tweezers. J. Opt. Soc. Am. 2017, 34, 38–43. [Google Scholar] [CrossRef]
- Determining Fluorescence Intensity and Signal. University of Meryland, Baltimore Country. Available online: https://kpif.umbc.edu/image-processing-resources/imagej-fiji/determining-fluorescence-intensity-and-positive-signal/ (accessed on 8 May 2022).
- Azab, A.K.; Runnels, J.M.; Pitsillides, C.; Moreau, A.S.; Azab, F.; Leleu, X.; Jia, X.; Wright, R.; Ospina, B.; Carlson, A.L.; et al. CXCR4 inhibitor AMD3100 disrupts the interaction of multiple myeloma cells with the bone marrow microenvironment and enhances their sensitivity to therapy. Blood 2009, 113, 4341–4351. [Google Scholar] [CrossRef] [Green Version]
- Dragoj, M.; Milosevic, Z.; Bankovic, J.; Tanic, N.; Pesic, M.; Stankovic, T. Targeting CXCR4 and FAK reverses dox-orubicin resistance and suppresses invasion in non-small cell lung carcinoma. Cell Oncol. 2017, 40, 47–62. [Google Scholar] [CrossRef] [PubMed]
- Choudhary, D.; Mossa, A.; Jadhav, M.; Cecconi, C. Bio-Molecular Applications of Recent Developments in Optical Tweezers. Biomolecules 2019, 9, 23. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yousafzai, M.S.; Coceano, G.; Mariutti, A.; Ndoye, F.; Amin, L.; Niemela, J.; Bonin, S.; Scoles, G.; Cojoc, D. Effect of neighboring cells on cell stiffness measured by optical tweezers indentation. J. Biomed. Opt. 2016, 21, 57004. [Google Scholar] [CrossRef] [Green Version]
- Jaiswal, D.; Cowley, N.; Bian, Z.; Zheng, G.; Claffey, K.P.; Hoshino, K. Stiffness analysis of 3D spheroids using microtweezers. PLoS ONE 2017, 12, e0188346. [Google Scholar] [CrossRef] [Green Version]
- Johansen, P.L.; Fenaroli, F.; Evensen, L.; Griffiths, G.; Koster, G. Optical micromanipulation of nanoparticles and cells inside living zebrafish. Nat. Commun. 2016, 7, 10974. [Google Scholar] [CrossRef] [Green Version]
- Staunton, J.R.; So, W.Y.; Paul, C.D.; Tanner, K. High-frequency microrheology in 3D reveals mismatch between cytoskeletal and extracellular matrix mechanics. Proc. Natl. Acad. Sci. USA 2019, 116, 14448–14455. [Google Scholar] [CrossRef] [Green Version]
- Wullkopf, L.; West, A.V.; Leijnse, N.; Cox, T.R.; Madsen, C.D.; Oddershede, L.B.; Erler, J.T. Cancer cells’ ability to mechanically adjust to extracellular matrix stiffness correlates with their invasive potential. Mol. Biol. Cell 2018, 29, 2378–2385. [Google Scholar] [CrossRef]
- Gupta, S.K.; Sun, J.; Han, Y.L.; Lyu, C.; He, T.; Guo, M. Quantification of Cell-Matrix Interaction in 3D Using Optical Tweezers. In Multi-Scale Extracellular Matrix Mechanics and Mechanobiology. Studies in Mechanobiology, Tissue Engineering and Biomaterials; Zhang, Y., Ed.; Springer: Berlin/Heidelberg, Germany, 2020; pp. 283–310. [Google Scholar]
- Ma, Z.; Liu, Q.; Yang, H.; Runyan, R.B.; Eisenberg, C.A.; Xu, M.; Borg, T.K.; Markwald, R.; Wang, Y.; Gao, B.Z. Laser patterning for the study of MSC cardiogenic differentiation at the single-cell level. Light. Sci. Appl. 2013, 2, 68. [Google Scholar] [CrossRef] [PubMed]
- Jordan, P.; Leach, J.; Padgett, M.; Blackburn, P.; Isaacs, N.; Goksör, M.; Hanstorp, D.; Wright, A.; Girkin, J.; Cooper, J. Creating permanent 3D arrangements of isolated cells using holographic optical tweezers. Lab Chip 2005, 5, 1224–1228. [Google Scholar] [CrossRef] [PubMed]
- Kirkham, G.R.; Britchford, E.; Upton, T.; Ware, J.; Gibson, G.M.; Devaud, Y.; Ehrbar, M.; Padgett, M.; Allen, S.; Buttery, L.D.; et al. Precision assembly of complex cellular microenvironments using holographic optical tweezers. Sci. Rep. 2015, 5, 8577. [Google Scholar] [CrossRef] [Green Version]
- Yoshida, A.; Tsuji, S.; Taniguchi, H.; Kenmotsu, T.; Sadakane, K.; Yoshikawa, K. Manipulating Living Cells to Construct a 3D Single-Cell Assembly without an Artificial Scaffold. Polymers 2017, 9, 319. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aziz, M.A.; Cabral, J.D.; Brooks, H.J.; McConnell, M.A.; Fitzpatrick, C.; Hanton, L.R.; Moratti, S.C. In vitro biocompatibility and cellular interactions of a chitosan/dextran-based hydrogel for postsurgical adhesion prevention. J. Biomed. Mater. Res. B Appl. Biomater. 2015, 103, 332–341. [Google Scholar] [CrossRef]
- Apollonio, B.; Ioannou, N.; Papazoglou, D.; Ramsay, A.G. Understanding the Immune-Stroma Microenvironment in B Cell Malignancies for Effective Immunotherapy. Front. Oncol. 2021, 11, 626818. [Google Scholar] [CrossRef]
- Senthebane, D.A.; Rowe, A.; Thomford, N.E.; Shipanga, H.; Munro, D.; Mazeedi, M.A.M.A.; Almazyadi, H.A.M.; Kallmeyer, K.; Dandara, C.; Pepper, M.S.; et al. The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer. Int. J. Mol. Sci. 2017, 18, 1586. [Google Scholar] [CrossRef] [Green Version]
- Adamo, A.; Delfino, P.; Gatti, A.; Bonato, A.; Takam Kamga, P.; Bazzoni, R.; Ugel, S.; Mercuri, A.; Caligola, S.; Krampera, M. HS-5 and HS-27A Stromal Cell Lines to Study Bone Marrow Mesenchymal Stromal Cell-Mediated Support to Cancer Development. Front. Cell Dev. Biol. 2020, 8, 584232. [Google Scholar] [CrossRef]
- Parrish, J.A.; Anderson, R.R.; Harrist, T.; Paul, B.; Murphy, G.F. Selective thermal effects with pulsed irradiation from lasers: From organ to organelle. J. Investig. Dermatol. 1983, 80, 75–80. [Google Scholar] [CrossRef]
- Kirkpatrick, J.B.; Higgins, M.L.; Lucas, J.H.; Gross, G.W. In vitro simulation of neural trauma by laser. J. Neuropathol. Exp. Neurol. 1985, 44, 268–284. [Google Scholar] [CrossRef]
- Ashkin, A.; Dziedzic, J.M.; Yamane, T. Optical trapping and manipulation of single cells using infrared laser beams. Nature 1987, 330, 769–771. [Google Scholar] [CrossRef] [PubMed]
- Keloth, A.; Anderson, O.; Risbridger, D.; Paterson, L. Single Cell Isolation Using Optical Tweezers. Micromachines 2018, 9, 434. [Google Scholar] [CrossRef] [PubMed]
- Recasens-Zorzo, C.; Cardesa-Salzmann, T.; Petazzi, P.; Ros-Blanco, L.; Esteve-Arenys, A.; Clot, G.; Guerrero-Hernández, M.; Rodríguez, V.; Soldini, D.; Valera, A.; et al. Pharmacological modulation of CXCR4 cooperates with BET bromodomain inhibition in diffuse large B-cell lymphoma. Haematologica 2019, 104, 778–788. [Google Scholar] [CrossRef] [PubMed]
- Moreno, M.J.; Bosch, R.; Dieguez-Gonzalez, R.; Novelli, S.; Mozos, A.; Gallardo, A.; Pavón, M.Á.; Céspedes, M.V.; Grañena, A.; Alcoceba, M.; et al. CXCR4 expression enhances diffuse large B cell lymphoma dissemination and decreases patient survival. J. Pathol. 2015, 235, 445–455. [Google Scholar] [CrossRef]
- Zlotnik, A.; Burkhardt, A.M.; Homey, B. Homeostatic chemokine receptors and organ-specific metastasis. Nat. Rev. Immunol. 2011, 11, 597–606. [Google Scholar] [CrossRef]
- Lenz, G.; Wright, G.; Dave, S.S.; Xiao, W.; Powell, J.; Zhao, H.; Xu, W.; Tan, B.; Goldschmidt, N.; Iqbal, J.; et al. Lymphoma/Leukemia Molecular Profiling Project. Stromal gene signatures in large-B-cell lymphomas. N. Engl. J. Med. 2008, 359, 2313–2323. [Google Scholar] [CrossRef] [Green Version]
- Domanska, U.M.; Timmer-Bosscha, H.; Nagengast, W.B.; Oude Munnink, T.H.; Kruizinga, R.C.; Ananias, H.J.; Kliphuis, N.M.; Huls, G.; De Vries, E.G.; de Jong, I.J.; et al. CXCR4 inhibition with AMD3100 sensitizes prostate cancer to docetaxel chemotherapy. Neoplasia 2012, 14, 709–718. [Google Scholar] [CrossRef] [Green Version]
- Liesveld, J.L.; Bechelli, J.; Rosell, K.; Lu, C.; Bridger, G.; Phillips, G., 2nd; Abboud, C.N. Effects of AMD3100 on transmigration and survival of acute myelogenous leukemia cells. Leuk. Res. 2007, 31, 1553–1563. [Google Scholar] [CrossRef] [Green Version]
- Hou, J.; Luo, T.; Ng, K.L.; Leung, A.Y.; Liang, R.; Sun, D. Characterization of Drug Effect on Leukemia Cells Through Single Cell Assay With Optical Tweezers and Dielectrophoresis. IEEE Trans. Nanobiosci. 2016, 15, 820–827. [Google Scholar] [CrossRef]
- Shen, Z.H.; Zeng, D.F.; Kong, P.Y.; Ma, Y.Y.; Zhang, X. AMD3100 and G-CSF disrupt the cross-talk between leukemia cells and the endosteal niche and enhance their sensitivity to chemotherapeutic drugs in biomimetic polystyrene scaffolds. Blood Cells Mol. Dis. 2016, 59, 1624. [Google Scholar] [CrossRef]
- Juarez, J.; Bradstock, K.F.; Gottlieb, D.J.; Bendall, L.J. Effects of inhibitors of the chemokine receptor CXCR4 on acute lymphoblastic leukemia cells in vitro. Leukemia 2003, 17, 1294–1300. [Google Scholar] [CrossRef] [PubMed]
- Cooper, T.M.; Sison, E.A.R.; Baker, S.D.; Li, L.; Ahmed, A.; Trippett, T.; Gore, L.; Macy, M.E.; Narendran, A.; August, K.; et al. A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators’ Consortium study (POE 10-03). Pediatr. Blood Cancer 2017, 64, e26414. [Google Scholar]
- Wang, S.; Wang, X.; Liu, S.; Zhang, S.; Wei, X.; Song, Y.; Yin, Q. The CXCR4 Antagonist, AMD3100, Reverses Mesenchymal Stem Cell-Mediated Drug Resistance in Relapsed/Refractory Acute Lymphoblastic Leukemia. OncoTargets Ther. 2020, 13, 6583–6591. [Google Scholar] [CrossRef]
- Uy, G.L.; Rettig, M.P.; Motabi, I.H.; McFarland, K.; Trinkaus, K.M.; Hladnik, L.M.; Kulkarni, S.; Abboud, C.N.; Cashen, A.F.; Stockerl-Goldstein, K.E.; et al. A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Blood 2012, 119, 3917–3924. [Google Scholar] [CrossRef] [PubMed]
- Roboz, G.J.; Ritchie, E.K.; Dault, Y.; Lam, L.; Marshall, D.C.; Cruz, N.M.; Hsu, H.C.; Hassane, D.C.; Christos, P.J.; Ippoliti, C.; et al. Phase I trial of plerixafor combined with decitabine in newly diagnosed older patients with acute myeloid leukemia. Haematologica 2018, 103, 1308–1316. [Google Scholar] [CrossRef]
- Regenbogen, S.; Stagno, M.J.; Schleicher, S.; Schilbach, K.; Bösmüller, H.; Fuchs, J.; Schmid, E.; Seitz, G. Cytotoxic drugs in combination with the CXCR4 antagonist AMD3100 as a potential treatment option for pediatric rhabdomyosarcoma. Int. J. Oncol. 2020, 57, 289–300. [Google Scholar] [CrossRef]
- Sison, E.A.; McIntyre, E.; Magoon, D.; Brown, P. Dynamic chemotherapy-induced upregulation of CXCR4 expression: A mechanism of therapeutic resistance in pediatric AML. Mol. Cancer Res. 2013, 11, 1004–1016. [Google Scholar] [CrossRef] [Green Version]
- Kim, M.; Koh, Y.J.; Kim, K.E.; Koh, B.I.; Nam, D.H.; Alitalo, K.; Kim, I.; Koh, G.Y. CXCR4 signaling regulates metastasis of chemoresistant melanoma cells by a lymphatic metastatic niche. Cancer Res. 2010, 70, 10411–10421. [Google Scholar] [CrossRef] [Green Version]
- Beji, S.; Milano, G.; Scopece, A.; Cicchillitti, L.; Cencioni, C.; Picozza, M.; D’Alessandra, Y.; Pizzolato, S.; Bertolotti, M.; Spaltro, G.; et al. Doxorubicin upregulates CXCR4 via miR-200c/ZEB1-dependent mechanism in human cardiac mesenchymal progenitor cells. Cell Death Dis. 2017, 24, e3020. [Google Scholar] [CrossRef]
- Xue, C.; Wang, X.; Zhang, L.; Qu, Q.; Zhang, Q.; Jiang, Y. Ibrutinib in B-cell lymphoma: Single fighter might be enough? Cancer Cell Int. 2020, 20, 467. [Google Scholar] [CrossRef]
- Herman, S.E.; Mustafa, R.Z.; Jones, J.; Wong, D.H.; Farooqui, M.; Wiestner, A. Treatment with Ibrutinib Inhibits BTK- and VLA-4-Dependent Adhesion of Chronic Lymphocytic Leukemia Cells In Vivo. Clin. Cancer Res. 2015, 21, 4642–4651. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Rooij, M.F.; Kuil, A.; Geest, C.R.; Eldering, E.; Chang, B.Y.; Buggy, J.J.; Pals, S.T.; Spaargaren, M. The clinically active BTK inhibitor PCI-32765 targets B-cell receptor- and chemokine-controlled adhesion and migration in chronic lymphocytic leukemia. Blood 2012, 119, 2590–2594. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Duś-Szachniewicz, K.; Gdesz-Birula, K.; Nowosielska, E.; Ziółkowski, P.; Drobczyński, S. Formation of Lymphoma Hybrid Spheroids and Drug Testing in Real Time with the Use of Fluorescence Optical Tweezers. Cells 2022, 11, 2113. https://doi.org/10.3390/cells11132113
Duś-Szachniewicz K, Gdesz-Birula K, Nowosielska E, Ziółkowski P, Drobczyński S. Formation of Lymphoma Hybrid Spheroids and Drug Testing in Real Time with the Use of Fluorescence Optical Tweezers. Cells. 2022; 11(13):2113. https://doi.org/10.3390/cells11132113
Chicago/Turabian StyleDuś-Szachniewicz, Kamila, Katarzyna Gdesz-Birula, Emilia Nowosielska, Piotr Ziółkowski, and Sławomir Drobczyński. 2022. "Formation of Lymphoma Hybrid Spheroids and Drug Testing in Real Time with the Use of Fluorescence Optical Tweezers" Cells 11, no. 13: 2113. https://doi.org/10.3390/cells11132113