Human Fetal Skin Fibroblast Isolation and Expansion for Clinical Application

  • Parisa Goodarzi
  • Hamid Reza Aghayan
  • Moloud Payab
  • Bagher Larijani
  • Sepideh Alavi-Moghadam
  • Masoumeh Sarvari
  • Hossein Adibi
  • Fatemeh Khatami
  • Najmeh Foroughi Heravani
  • Mahdieh Hadavandkhani
  • Babak ArjmandEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 2109)


Cell therapy is one of the most hopeful technologies of regenerative medicine approaches. Among various cells, human skin fibroblasts have been progressively used for wound healing as cell-based therapy purposes. By increasing the age, the number of skin fibroblasts’ abilities including cell migration, growth, collagen production, etc. decreases. Hence, use of the fetal source is more beneficent. In this respect, this chapter covers the manufacturing of human fetal skin-derived fibroblasts for clinical application.


Fibroblasts Fetal tissue Cell isolation Culture Therapeutic use 



Basic fibroblast growth factor


Cell-based medicinal products


Cluster of differentiation


Current good manufacturing practice


Committee for Proprietary Medicinal Product


Committee for Medicinal Products for Veterinary Use


Dulbecco’s Modified Eagle’s Medium-low glucose


Dimethyl sulfoxide


European Medicines Agency


Fetal bovine serum


Hepatitis B virus


Hepatitis C virus


High efficiency particulate air


Human immunodeficiency virus




Last menstrual period


Phosphate-buffered saline




Rapid plasma reagin


Reverse transcription polymerase chain reaction


Standard operating procedure


Transmissible spongiform encephalopathy



The authors would like to thank Dr. Mohsen Khorshidi, Shokouh Salimi, Maryam Afshari, and Ali Valadkhani for their considerable assistance.


  1. 1.
    Mao AS, Mooney DJ (2015) Regenerative medicine: current therapies and future directions. Proc Natl Acad Sci U S A 112(47):14452–14459CrossRefGoogle Scholar
  2. 2.
    Larijani B, Aghayan HR, Goodarzi P et al (2015) GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation. Methods Mol Biol 1283:123–136CrossRefGoogle Scholar
  3. 3.
    Costa-Almeida R, Soares R, Granja PL (2018) Fibroblasts as maestros orchestrating tissue regeneration. J Tissue Eng Regen Med 12(1):240–251CrossRefGoogle Scholar
  4. 4.
    Alberts B, Johnson A, Lewis J et al (2002) Fibroblasts and their transformations: the connective-tissue cell family. Garland Science, New YorkGoogle Scholar
  5. 5.
    Ellis I, Banyard J, Schor SL (1997) Differential response of fetal and adult fibroblasts to cytokines: cell migration and hyaluronan synthesis. Development 124(8):1593–1600PubMedGoogle Scholar
  6. 6.
    Chen WY, Grant ME, Schor AM et al (1989) Differences between adult and foetal fibroblasts in the regulation of hyaluronate synthesis: correlation with migratory activity. J Cell Sci 94(Pt 3):577–584PubMedGoogle Scholar
  7. 7.
    Goodarzi P, Falahzadeh K, Aghayan H et al (2018) GMP-compliant human fetal skin fibroblasts for wound healing. Arch Neurosci 5(3):e68497CrossRefGoogle Scholar
  8. 8.
    Larijani B, Ghahari A, Warnock G et al (2015) Human fetal skin fibroblasts: extremely potent and allogenic candidates for treatment of diabetic wounds. Med Hypotheses 84(6):577–579CrossRefGoogle Scholar
  9. 9.
    Larijani B, Arjmand B, Amoli MM et al (2012) Establishing a cGMP pancreatic islet processing facility: the first experience in Iran. Cell Tissue Bank 13(4):569–575CrossRefGoogle Scholar
  10. 10.
    Sekiya EJ, Forte A, Kühn TIBB et al (2012) Establishing a stem cell culture laboratory for clinical trials. Rev Bras Hematol Hemoter 34(3):236–241CrossRefGoogle Scholar
  11. 11.
    Whyte W (2010) Cleanroom technology: fundamentals of design, testing and operation. Wiley, HobokenGoogle Scholar
  12. 12.
    Kahn JB, Bourne JP, Tyler CW et al (1971) The impact of recent changes in therapeutic abortion laws. Clin Obstet Gynecol 14(4):1130–1148CrossRefGoogle Scholar
  13. 13.
    Abbasi M, Shamsi Gooshki E, Allahbedashti N (2014) Abortion in Iranian legal system: a review. Iran J Allergy Asthma Immunol 13(1):71–84PubMedGoogle Scholar
  14. 14.
    Omani SR (2013) Therapeutic abortion law in Iran: past, present and future (ethics and reproductive health). Int J Fertil Steril 7(Suppl 1):15 Google Scholar
  15. 15.
    Jehan I, Zaidi S, Rizvi S et al (2010) Dating gestational age by last menstrual period, symphysis-fundal height, and ultrasound in urban Pakistan. Int J Gynaecol Obstet 110(3):231–234CrossRefGoogle Scholar
  16. 16.
    Karumbayaram S, Lee P, Azghadi SF et al (2012) From skin biopsy to neurons through a pluripotent intermediate under good manufacturing practice protocols. Stem Cells Transl Med 1(1):36–43CrossRefGoogle Scholar
  17. 17.
    Giancola R, Bonfini T, Iacone A (2012) Cell therapy: cGMP facilities and manufacturing. Muscles Ligaments Tendons J 2(3):243–247PubMedPubMedCentralGoogle Scholar
  18. 18.
    Aghayan HR, Mahdavi-Mazdeh M, Goodarzi P et al (2010) Coding and traceability in Iran. Cell Tissue Bank 11(4):397–400CrossRefGoogle Scholar
  19. 19.
    De Sousa PA, Downie JM, Tye BJ et al (2016) Development and production of good manufacturing practice grade human embryonic stem cell lines as source material for clinical application. Stem Cell Res 17(2):379–390CrossRefGoogle Scholar
  20. 20.
    Bieback K, Schallmoser K, Klüter H et al (2008) Clinical protocols for the isolation and expansion of mesenchymal stromal cells. Transfus Med Hemother 35(4):286–294CrossRefGoogle Scholar
  21. 21.
    Aghayan HR, Goodarzi P, Arjmand B (2015) GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular therapy. Methods Mol Biol 1283:93–107CrossRefGoogle Scholar
  22. 22.
    Lupatov AY, Vdovin AS, Vakhrushev IV et al (2015) Comparative analysis of the expression of surface markers on fibroblasts and fibroblast-like cells isolated from different human tissues. Bull Exp Biol Med 158(4):537–543CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2019

Authors and Affiliations

  • Parisa Goodarzi
    • 1
  • Hamid Reza Aghayan
    • 2
  • Moloud Payab
    • 3
  • Bagher Larijani
    • 4
  • Sepideh Alavi-Moghadam
    • 5
  • Masoumeh Sarvari
    • 2
  • Hossein Adibi
    • 6
  • Fatemeh Khatami
    • 7
  • Najmeh Foroughi Heravani
    • 2
  • Mahdieh Hadavandkhani
    • 2
  • Babak Arjmand
    • 2
    • 5
    Email author
  1. 1.Brain and Spinal Cord Injury Research CenterNeuroscience Institute, Tehran University of Medical SciencesTehranIran
  2. 2.Cell Therapy and Regenerative Medicine Research CenterEndocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical SciencesTehranIran
  3. 3.Obesity and Eating Habits Research CenterEndocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical SciencesTehranIran
  4. 4.Endocrinology and Metabolism Research CenterEndocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciencesTehranIran
  5. 5.Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical SciencesTehranIran
  6. 6.Diabetes Research CenterEndocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical SciencesTehranIran
  7. 7.Chronic Diseases Research CenterEndocrinology and Metabolism Population Sciences Institute, Tehran University of Medical SciencesTehranIran

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