Cell line

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Definition

A cell line is a population of cells derived from a few cells of a multicellular organism, generated in vitro from primary culture after the first passage. The cell line contains genetic information identical to the organism from which it was derived. Cell lines derived from normal (non-cancerous) cells and tissues have a limited ability for division and can be maintained in culture for a limited time. The number of passages of cell line depends on the type of tissue and age of the organism from which the cell line was derived, and the limited number of cell divisions reflects in vivo aging of cells. Cell lines derived from stem cells (embryonic, adult or induced) or immortalised cells, avoid cellular senescence caused by a mutation, and live longer. Compared to animal models, cell lines are cheaper and easier to maintain, able to provide more reproducible results, and usually (with the exception of embryonic cells) are not burdened with ethical controversy, which makes them an attractive material for biological and medical research. However, it is necessary to remember that cell lines derived from a small number of cells are susceptible to genetic changes over the time of extended culture and number of passages, cell lines may not always adequately represent the properties of the primary cell populations. Cell lines with an unlimited life-span and the ability to divide indefinitely can be derived from cancerous tumors.[1]

Stem cell lines

Embryonic stem cells (ESC) are pluripotent (capable of differentiating into all cell types existing in the body). They are typically isolated from the inner cell mass of a pre-implantation embryo (blastocyst stage), which raises ethical concerns and has prompted researchers to turn to other sources of stem cells, such as somatic stem cells which naturally exists in the adult body. Somatic cells are both multipotent cells (e.g. hematopoietic cells or mesenchymal stem cells) and unipotent cells (e.g. skeletal muscle satellite cells). The isolation of somatic stem cells is well documented, many of them have been used to generate cell lines for research on a new cellular therapies in regenerative medicine. In search of new research opportunities for stem cells, adult specialized somatic cells were "reprogrammed" into induced pluripotent stem cell (iPSC) lines capable of producing any type of cells. The induction of somatic cells to revert to a pluripotent stem cell state was achieved by the introduction of four factors: the Oct3/4, Sox2, c-Myc and Klf4 genes. Apart from eliminating the ethical concerns arising from the use of ESCs, another advantage of lines derived from somatic cells is that in potential therapeutic purposes, e.g. in regenerative medicine or tissue engineering, they can be derived from the patient, making them an easily obtainable and physiologically compatible with the recipient's organism that enables their potential use in personalized cell therapy.[2] [3] [4] [5] [6]

Immortalised cell lines

The mutations that cause the cell immortalisation can occur naturally – such is in the case of cell lines derived from cancers, e.g. in the first human cell line, HeLa, or can be induced under laboratory conditions by chemical or oncogene mediated transformation. In the latter case, this is achieved by overexpressing telomerase and TERT, inactivating cell cycle checkpoints p53 and pRb, or introducing oncogenes or viral vectors encoding oncoproteins, which also interfere with cell cycle regulators. There is, however, a risk of undesired carcinogenic effects when using immortalised cells.[7] [8]

Bibliography

  1. Stokłosowa S.: Hodowla komórek i tkanek. Warszawa: Wydawnictwo Naukowe PWN, 2004.
  2. Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006 Aug 25;126(4):663-76. doi: 10.1016/j.cell.2006.07.024.
  3. Kim JS, Choi HW, Choi S, Do JT. Reprogrammed pluripotent stem cells from somatic cells. Int J Stem Cells. 2011 Jun;4(1):1-8. doi: 10.15283/ijsc.2011.4.1.1.
  4. Danisovic L, Culenova M, Csobonyeiova M. Induced Pluripotent Stem Cells for Duchenne Muscular Dystrophy Modeling and Therapy. Cells. 2018 Dec 7;7(12):253. doi: 10.3390/cells7120253.
  5. Zahumenska R, Nosal V, Smolar M, Okajcekova T, Skovierova H, Strnadel J, Halasova E. Induced Pluripotency: A Powerful Tool for In Vitro Modeling. Int J Mol Sci. 2020 Nov 24;21(23):8910. doi: 10.3390/ijms21238910.
  6. Seminary ER, Santarriaga S, Wheeler L, Mejaki M, Abrudan J, Demos W, Zimmermann MT, Urrutia RA, Fee D, Barkhaus PE, Ebert AD. Motor Neuron Generation from iPSCs from Identical Twins Discordant for Amyotrophic Lateral Sclerosis. Cells. 2020 Feb 28;9(3):571. doi: 10.3390/cells9030571.
  7. Paprocka M, Krawczenko A, Dus D, Kantor A, Carreau A, Grillon C, Kieda C. CD133 positive progenitor endothelial cell lines from human cord blood. Cytometry A. 2011 Aug;79(8):594-602. doi: 10.1002/cyto.a.21092. Epub 2011 Jun 27.
  8. Katsumiti A, Ruenraroengsak P, Cajaraville MP, Thorley AJ, Tetley TD. Immortalisation of primary human alveolar epithelial lung cells using a non-viral vector to study respiratory bioreactivity in vitro. Sci Rep. 2020 Nov 24;10(1):20486. doi: 10.1038/s41598-020-77191-y.