ORIGINAL RESEARCH

Telomerized fibroblasts as a candidate 3D in vitro model of pathological hypertrophic scars

Shadrin VS, Kozhin PM, Shoshina OO, Luzgina NG, Rusanov AL
About authors

Orekhovich Research Institute of Biomedical Chemistry, Moscow, Russia

Correspondence should be addressed: Valerian S. Shadrin
Pogodinskaya, 10, str. 8, Moscow, 119121; moc.liamg@nirdahsnairelav

About paper

Funding: this research was supported by the Russian Ministry of Science and Higher Education and was conducted under the Federal Targeted Program on Research and Development in Priority Fields of Science and Technology for 2014–2020 (Agreement 05.604.21.0219, Project ID RFMEFI60419X0219).

Author contribution: Luzgina NG, Rusanov AL conceived the study and proposed its design; Shadrin VS, Kozhin PM, Shoshina OO, Luzgina NG, Rusanov AL analyzed the literature, analyzed and interpreted the experimental data and wrote the manuscript; Shadrin VS, Kozhin PM planned and conducted the experiment; Shadrin VS wrote the manuscript.

Received: 2020-08-28 Accepted: 2020-09-02 Published online: 2020-09-27
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  1. Jumper N, Paus R, Bayat A. Functional histopathology of keloid disease. Histology and histopathology. 2015; 30 (9): 1033–57.
  2. Sidgwick GP, Bayat A. Extracellular matrix molecules implicated in hypertrophic and keloid scarring. Journal of the European Academy of Dermatology and Venereology. 2012; 26 (2): 141–152.
  3. Liang CJ, Yen YH, Hung LY, Wang SH, Pu CM, Chien HF, et al. Thalidomide inhibits fibronectin production in TGF-β1-treated normal and keloid fibroblasts via inhibition of the p38/Smad3 pathway. Biochemical pharmacology. 2013; 85 (11): 1594–02.
  4. De Felice B, Wilson RR, Nacca M. Telomere shortening may be associated with human keloids. BMC medical genetics. 2009; 10 (1): 110.
  5. Huang Y, Lin LX, Bi QX, Wang P, Wang XM, Liu J, et al. Effects of hTERT antisense oligodeoxynucleotide on cell apoptosis and expression of hTERT and bcl-2 mRNA in keloid fibroblasts. European Review for Medical and Pharmacological Sciences. 2017; 21 (8): 1944–51.
  6. Yu D, Shang Y, Yuan J, Ding S, Luo S, Hao L. Wnt/β-catenin signaling exacerbates keloid cell proliferation by regulating telomerase. Cellular Physiology and Biochemistry. 2016; 39 (5): 2001–13.
  7. Kischer CW, Thies AC, Chvapil M. Perivascular myofibroblasts and microvascular occlusion in hypertrophic scars and keloids. Human pathology. 1982; 13 (9): 819–24.
  8. Bran GM, Goessler UR, Hormann K, Riedel F, Sadick H. Keloids: current concepts of pathogenesis. International journal of molecular medicine. 2009; 24 (3): 283–93
  9. Chin D, Boyle GM, Parsons PG, Coman WB. What is transforming growth factor-beta (TGF-β)?. British journal of plastic surgery. 2004; 57 (3): 215–21.
  10. Yang GP, Lim IJ, Phan TT, Lorenz HP, Longaker MT. From scarless fetal wounds to keloids: molecular studies in wound healing. Wound repair and regeneration. 2003; 11 (6): 411–8.
  11. Jagadeesan J, Bayat A. Transforming growth factor beta (TGFβ) and keloid disease. International journal of surgery. 2007; 5 (4): 278–85.
  12. Egorov EE, Terekhov SM, Vishniakova K, Karachentsev DN, Kazimirchuk EV, Tsvetkova TG, et al. Telomerization as a method of obtaining immortal human cells preserving normal properties. Ontogenez. 2003; 34 (3): 183.
  13. Kupcsik L. Estimation of cell number based on metabolic activity: the MTT reduction assay. In Mammalian cell viability. Humana Press. 2011: 13–19.
  14. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nature methods. 2012; 9 (7): 676–82.
  15. Carpenter AE, Jones TR., Lamprecht MR, Clarke C, Kang IH, Friman O, et al. CellProfiler: image analysis software for identifying and quantifying cell phenotypes. Genome biology. 2006; 7 (10): R100.
  16. Lee TY, Chin GS, Kim W, Chau D, Gittes GK, Longaker MT. Expression of transforming growth factor beta 1, 2, and 3 proteins in keloids. Annals of plastic surgery. 1999; 43 (2): 179–84.
  17. Klass BR, Grobbelaar AO, Rolfe KJ. Transforming growth factor β1 signalling, wound healing and repair: a multifunctional cytokine with clinical implications for wound repair, a delicate balance. Postgraduate Medical Journal. 2009; 85 (999): 9–14.
  18. Friedrich J, Ebner R, Kunz-Schughart LA. Experimental anti-tumor therapy in 3-D: spheroids–old hat or new challenge? International journal of radiation biology. 2007; 83 (11–12): 849–71.
  19. Ohno M, Abe T. Rapid colorimetric assay for the quantification of leukemia inhibitory factor (LIF) and interleukin-6 (IL-6). Journal of immunological methods. 1991; 145 (1–2): 199–203.
  20. Meran S, Thomas DW, Stephens P, Enoch S, Martin J, Steadman R, et al. Hyaluronan facilitates transforming growth factor-β1-mediated fibroblast proliferation. Journal of Biological Chemistry. 2008; 283 (10): 6530–45.
  21. Negreros M, Hagood JS, Espinoza CR, Balderas-Martínez YI, Selman M, Pardo A. Transforming growth factor beta 1 induces methylation changes in lung fibroblasts. PloS one. 2019; 14 (10): e0223512.
  22. Takezawa T, Mori Y, Yonaha T, Yoshizato K. Characterization of morphology and cellular metabolism during the spheroid formation by fibroblasts. Experimental cell research. 1993; 208 (2): 430–41.
  23. Frandsen SK, Gibot L, Madi M, Gehl J, Rols MP. Calcium electroporation: evidence for differential effects in normal and malignant cell lines, evaluated in a 3D spheroid model. PLoS One. 2015; 10 (12): e0144028.
  24. Mittler F, Obeïd P, Rulina AV, Haguet V, Gidrol X, Balakirev MY. High-content monitoring of drug effects in a 3D spheroid model. Frontiers in oncology. 2017; 7: 293.
  25. Tuan TL, Wu H, Huang EY, Chong SS, Laug W, Messadi D, et al. Increased plasminogen activator inhibitor-1 in keloid fibroblasts may account for their elevated collagen accumulation in fibrin gel cultures. The American journal of pathology. 2003; 162 (5): 1579–89.