Immunosuppressive Mesenchymal Stem Cells Aggregates Incorporating Hydrogel Microspheres Promote an In vitro Invasion of Cancer Cells

Overview

Journal Regen Ther

Date 2022 Jan 3

PMID 34977285

Citations 6

Authors

Teruki Nii

Yasuhiko Tabata

Affiliations

Soon will be listed here.

Abstract

Introduction: The objective of this study is to design a co-culture system of cancer cells and three-dimensional (3D) mesenchymal stem cells (MSC) aggregates for the in vitro evaluation of cancer invasion.

Methods: First, the MSC of an immunosuppressive phenotype (MSC2) were prepared by the MSC stimulation of polyriboinosinic polyribocytidylic acid. By simple mixing MSC2 and gelatin hydrogel microspheres (GM) in a U-bottomed well of 96 well plates which had been pre-coated with poly (vinyl alcohol), 3D MSC2 aggregates incorporating GM were obtained. The amount of chemokine (C-C motif) ligand 5 (CCL5) secreted from the MSC2 aggregates incorporating GM. Finally, an invasion assay was performed to evaluate the cancer invasion rate by co-cultured cancer cells and the 3D MSC2 incorporating GM.

Results: The amount of CCL5 secreted for the 3D MSC2 aggregates incorporating GM was significantly higher than that of two-dimensional (2D) MSC, 2D MSC2, and 3D MSC aggregates incorporating GM. When MDA-MB-231 human breast cancer cells were co-cultured with the 3D MSC2 aggregates incorporating GM, the invasion rate of cancer cells was significantly high compared with that of 2D MSC or 2D MSC2 and 3D MSC aggregates incorporating GM. In addition, high secretion of matrix metalloproteinase-2 was observed for the 3D MSC2 aggregates/cancer cells system.

Conclusions: It is concluded that the co-culture system of 3D MSC2 aggregates incorporating GM and cancer cells is promising to evaluate the invasion of cancer cells in vitro.

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References

Tomita T, Sakurai Y, Ishibashi S, Maru Y . Imbalance of Clara cell-mediated homeostatic inflammation is involved in lung metastasis. Oncogene. 2011; 30(31):3429-39. DOI: 10.1038/onc.2011.53. View

Nii T, Makino K, Tabata Y . Influence of shaking culture on the biological functions of cell aggregates incorporating gelatin hydrogel microspheres. J Biosci Bioeng. 2019; 128(5):606-612. DOI: 10.1016/j.jbiosc.2019.04.013. View

Baker A, Tam R, Shoichet M . Independently Tuning the Biochemical and Mechanical Properties of 3D Hyaluronan-Based Hydrogels with Oxime and Diels-Alder Chemistry to Culture Breast Cancer Spheroids. Biomacromolecules. 2017; 18(12):4373-4384. DOI: 10.1021/acs.biomac.7b01422. View

Bello A, Kim D, Kim D, Park H, Lee S . Engineering and Functionalization of Gelatin Biomaterials: From Cell Culture to Medical Applications. Tissue Eng Part B Rev. 2020; 26(2):164-180. DOI: 10.1089/ten.TEB.2019.0256. View

Reynolds D, Tevis K, Blessing W, Colson Y, Zaman M, Grinstaff M . Breast Cancer Spheroids Reveal a Differential Cancer Stem Cell Response to Chemotherapeutic Treatment. Sci Rep. 2017; 7(1):10382. PMC: 5583341. DOI: 10.1038/s41598-017-10863-4. View

Abecasis B, Aguiar T, Arnault E, Costa R, Gomes-Alves P, Aspegren A . Expansion of 3D human induced pluripotent stem cell aggregates in bioreactors: Bioprocess intensification and scaling-up approaches. J Biotechnol. 2017; 246:81-93. DOI: 10.1016/j.jbiotec.2017.01.004. View

Moriyama K, Naito S, Wakabayashi R, Goto M, Kamiya N . Enzymatically prepared redox-responsive hydrogels as potent matrices for hepatocellular carcinoma cell spheroid formation. Biotechnol J. 2016; 11(11):1452-1460. DOI: 10.1002/biot.201600087. View

Ikada , Tabata . Protein release from gelatin matrices. Adv Drug Deliv Rev. 2000; 31(3):287-301. DOI: 10.1016/s0169-409x(97)00125-7. View

Compan V, Guzman J, Riande E . A potentiostatic study of oxygen transmissibility and permeability through hydrogel membranes. Biomaterials. 1999; 19(23):2139-45. DOI: 10.1016/s0142-9612(98)00113-6. View

10.

Hinderer S, Layland S, Schenke-Layland K . ECM and ECM-like materials - Biomaterials for applications in regenerative medicine and cancer therapy. Adv Drug Deliv Rev. 2015; 97:260-9. DOI: 10.1016/j.addr.2015.11.019. View

11.

Lv D, Yu S, Ping Y, Wu H, Zhao X, Zhang H . A three-dimensional collagen scaffold cell culture system for screening anti-glioma therapeutics. Oncotarget. 2016; 7(35):56904-56914. PMC: 5302961. DOI: 10.18632/oncotarget.10885. View

12.

Eckstein N, Servan K, Hildebrandt B, Politz A, von Jonquieres G, Wolf-Kummeth S . Hyperactivation of the insulin-like growth factor receptor I signaling pathway is an essential event for cisplatin resistance of ovarian cancer cells. Cancer Res. 2009; 69(7):2996-3003. DOI: 10.1158/0008-5472.CAN-08-3153. View

13.

Desai P, Tseng H, Souza G . Assembly of Hepatocyte Spheroids Using Magnetic 3D Cell Culture for CYP450 Inhibition/Induction. Int J Mol Sci. 2017; 18(5). PMC: 5454994. DOI: 10.3390/ijms18051085. View

14.

Rodriguez-Enriquez S, Gallardo-Perez J, Aviles-Salas A, Marin-Hernandez A, Carreno-Fuentes L, Maldonado-Lagunas V . Energy metabolism transition in multi-cellular human tumor spheroids. J Cell Physiol. 2008; 216(1):189-97. DOI: 10.1002/jcp.21392. View

15.

Peng W, Logan C, Fish M, Anbarchian T, Aguisanda F, Alvarez-Varela A . Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture. Cell. 2018; 175(6):1607-1619.e15. PMC: 6497386. DOI: 10.1016/j.cell.2018.11.012. View

16.

Sica A, Schioppa T, Mantovani A, Allavena P . Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006; 42(6):717-27. DOI: 10.1016/j.ejca.2006.01.003. View

17.

Lin R, Lin R, Chang H . Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol J. 2008; 3(9-10):1172-84. DOI: 10.1002/biot.200700228. View

18.

Liu W, Song J, Du X, Zhou Y, Li Y, Li R . AKR1B10 (Aldo-keto reductase family 1 B10) promotes brain metastasis of lung cancer cells in a multi-organ microfluidic chip model. Acta Biomater. 2019; 91:195-208. DOI: 10.1016/j.actbio.2019.04.053. View

19.

Tabata Y, Ikada Y . Vascularization effect of basic fibroblast growth factor released from gelatin hydrogels with different biodegradabilities. Biomaterials. 1999; 20(22):2169-75. DOI: 10.1016/s0142-9612(99)00121-0. View

20.

Pedraza E, Coronel M, Fraker C, Ricordi C, Stabler C . Preventing hypoxia-induced cell death in beta cells and islets via hydrolytically activated, oxygen-generating biomaterials. Proc Natl Acad Sci U S A. 2012; 109(11):4245-50. PMC: 3306668. DOI: 10.1073/pnas.1113560109. View