Biology:Hybrid cell line

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A hybrid cell line is a fusion of cells from two different cell types. When the membrane of two cells merge, the nuclei combine to form a polykaryote (poly- multiple; karyon- chromosome).[1] These fusions can happen spontaneously as in the case of tumor hybrid cells, or may be induced by a variety of laboratory techniques. The first instance of intentionally generated hybrid cells was described in 1960 by Barski, Sorieul, and Cornefert in their paper "Production of cells of a 'hybrid' nature in cultures in vitro of 2 cellular strains in combination," originally published in French.[2] Today, one purpose of generating hybrid cell lines is to fuse cells that secrete a useful product with an immortal cell line to maximize the secretions. For example, immunoglobin-producing B lymphocytes can be fused with myeloma to produce an immortal line of cells called hybridoma that secrete immunoglobin. Hybrid cell lines are also used to study cancer and map genes[3]

Generating hybrid cells

The three most common methods of fusing cells to make a hybrid line are via oncogenic viruses, polyethylene glycol, or electrofusion.[1]

Oncogenic viruses

Certain oncogenic viruses encode for fusogens, which are proteins that encourage two cell membranes to fuse. When the viral genes are expressed by the host cell, the membranes of two cells may fuse.[4]

Some oncogenic viruses that code for fusogens and are capable of hybridizing cells are:

The virus used in laboratories for controlled cell hybridization is inactivated Sendai virus.[1]

Polyethylene glycol

Using polyethylene glycol is the method for inducing cell hybridization that requires the fewest steps. Polyethylene glycol functions by changing the direction and configuration of lipid molecules in the cell membrane, which increases their permeability and allows two membranes to fuse. Because of the low specificity of polyethylene glycol, it may be toxic to the cell.[3]

Electrofusion

When exposed to an alternating electric field, cells in suspension will line up like a chain along the electrical field lines. This is due to a phenomenon known as dielectrophoresis. After the cells are aligned, a pulse voltage around 10V can be applied, causing the membranes of these cells to fuse. The cells will homogenate into a single cell.[5]

Examples of hybrid cell lines

  • Hybridoma: a fusion of B-cells and immortal cancer cells with the purpose of generating antibodies.[6]
  • Tumor hybrid cells: fusion of tumor cells with normal bodily cells.[7][8] These tend to take on new properties which make them more difficult to treat.[9]
  • Human-mouse hybrid cells, i.e. HeLa/mouse hybrid.[10] These can be used as a diagnostic tool for conditions such as aneuploidy, but this is a dated technique that is rarely applied anymore.[11]
  • Humsters: a hybrid of human sperm and hamster eggs. These are created as a byproduct of fertility testing, when human sperm potency is measured by how well it can penetrate a hamster egg cell (hamster eggs tend to have similar penetrability to human sperm as do human eggs).[12] For more information, see semen analysis.


References

  1. ↑ 1.0 1.1 1.2 Nims, Raymond W.; Capes-Davis, Amanda; Reid, Christopher Korch and Yvonne A. (2018-11-05) (in en). Authenticating Hybrid Cell Lines. IntechOpen. ISBN 978-1-78984-867-0. https://www.intechopen.com/chapters/63598. 
  2. ↑ Ephrussi, B; Weiss, M C (May 1965). "Interspecific hybridization of somatic cells.". Proceedings of the National Academy of Sciences of the United States of America 53 (5): 1040–1042. doi:10.1073/pnas.53.5.1040. ISSN 0027-8424. PMID 5222546. 
  3. ↑ 3.0 3.1 Pedrazzoli, Filippo; Chrysantzas, Iraklis; Dezzani, Luca; Rosti, Vittorio; Vincitorio, Massimo; Sitar, Giammaria (December 2011). "Cell fusion in tumor progression: the isolation of cell fusion products by physical methods" (in en). Cancer Cell International 11 (1): 32. doi:10.1186/1475-2867-11-32. ISSN 1475-2867. PMID 21933375. 
  4. ↑ Gao, Peng; Zheng, Jie (2011-04-01). "Oncogenic virus-mediated cell fusion: New insights into initiation and progression of oncogenic viruses-related cancers" (in en). Cancer Letters 303 (1): 1–8. doi:10.1016/j.canlet.2010.12.021. ISSN 0304-3835. PMID 21306823. 
  5. ↑ Scheurich, Peter; Zimmermann, Ulrich; Mischel, Maja; Lamprecht, Ingolf (1980-12-01). "Membrane Fusion and Deformation of Red Blood Cells by Electric Fields" (in en). Zeitschrift für Naturforschung C 35 (11–12): 1081–1085. doi:10.1515/znc-1980-11-1236. ISSN 1865-7125. PMID 7210806. 
  6. ↑ Mitra, Sanchita; Tomar, Pushpa Chaudhary (December 2021). "Hybridoma technology; advancements, clinical significance, and future aspects" (in en). Journal of Genetic Engineering and Biotechnology 19 (1): 159. doi:10.1186/s43141-021-00264-6. ISSN 2090-5920. PMID 34661773. 
  7. ↑ Gast, Charles E.; Silk, Alain D.; Zarour, Luai; Riegler, Lara; Burkhart, Joshua G.; Gustafson, Kyle T.; Parappilly, Michael S.; Roh-Johnson, Minna et al. (2018-09-07). "Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival" (in en). Science Advances 4 (9): eaat7828. doi:10.1126/sciadv.aat7828. ISSN 2375-2548. PMID 30214939. 
  8. ↑ Brito, Ariadna; Merle, Candice; Lagarde, Pauline; Faustin, Benjamin; Devin, Anne; Lartigue, Lydia; Chibon, Frederic (2021-07-28). "Cell fusion enhances energy metabolism of mesenchymal tumor hybrid cells to sustain their proliferation and invasion". BMC Cancer 21 (1): 863. doi:10.1186/s12885-021-08561-6. ISSN 1471-2407. PMID 34320948. 
  9. ↑ Tretyakova, Maria S.; Subbalakshmi, Ayalur R.; Menyailo, Maxim E.; Jolly, Mohit Kumar; Denisov, Evgeny V. (2022-02-15). "Tumor Hybrid Cells: Nature and Biological Significance". Frontiers in Cell and Developmental Biology 10: 814714. doi:10.3389/fcell.2022.814714. ISSN 2296-634X. PMID 35242760. 
  10. ↑ Harris, Henry; Watkins, J. F. (February 1965). "Hybrid Cells Derived from Mouse and Man : Artificial Heterokaryons of Mammalian Cells from Different Species" (in en). Nature 205 (4972): 640–646. doi:10.1038/205640a0. ISSN 0028-0836. PMID 14287398. https://rdcu.be/c97WM. 
  11. ↑ Athwal, Raghbir S.; Sandhu, Shahbeg S. (1985-03-01). "Use of human × mouse hybrid cell line to detect aneuploidy induced by environmental chemicals" (in en). Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 149 (1): 73–81. doi:10.1016/0027-5107(85)90011-9. ISSN 0027-5107. PMID 3974624. https://dx.doi.org/10.1016/0027-5107%2885%2990011-9. 
  12. ↑ Hwang, Kathleen; Lamb, Dolores J. (2013), Carrell, Douglas T.; Aston, Kenneth I., eds., "The Sperm Penetration Assay for the Assessment of Fertilization Capacity" (in en), Spermatogenesis, Methods in Molecular Biology (Totowa, NJ: Humana Press) 927: pp. 103–111, doi:10.1007/978-1-62703-038-0_10, ISBN 978-1-62703-037-3, PMID 22992907 



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