Archives of Neuroscience

Published by: Kowsar

GMP-Compliant Human Fetal Skin Fibroblasts for Wound Healing

Parisa Goodarzi 1 , Khadijeh Falahzadeh 2 , Hamidreza Aghayan 3 , Fereshteh Mohamadi Jahani 1 , Moloud Payab 4 , Kambiz Gilany 2 , 5 , Fakher Rahim 6 , Bagher Larijani 7 , Akram Tayanloo Beik 3 , Hossein Adibi 8 and Babak Arjmand 2 , 3 , *
Authors Information
1 Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, IR Iran
2 Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, IR Iran
3 Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, IR Iran
4 Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, IR Iran
5 Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IR Iran
6 Health Research Institute, Thalassemia and Hemoglobinopathy Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, IR Iran
7 Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, IR Iran
8 Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, IR Iran
Article information
  • Archives of Neuroscience: July 2018, 5 (3); e68497
  • Published Online: July 14, 2018
  • Article Type: Research Article
  • Received: March 10, 2018
  • Revised: May 18, 2018
  • Accepted: July 4, 2018
  • DOI: 10.5812/ans.68497

To Cite: Goodarzi P, Falahzadeh K, Aghayan H, Mohamadi Jahani F, Payab M, et al. GMP-Compliant Human Fetal Skin Fibroblasts for Wound Healing, Arch Neurosci. 2018 ; 5(3):e68497. doi: 10.5812/ans.68497.

Copyright © 2018, Archives of Neuroscience. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited
1. Background
2. Methods
3. Results
4. Discussion
  • 1. Ho S, Marcal H, Foster LJ. Towards scarless wound healing: a comparison of protein expression between human, adult and foetal fibroblasts. Biomed Res Int. 2014;2014:676493. doi: 10.1155/2014/676493. [PubMed: 24605334]. [PubMed Central: PMC3925539].
  • 2. Parekh A, Hebda PA. The Contractile Phenotype of Dermal Fetal Fibroblasts in Scarless Wound Healing. Curr Pathobiol Rep. 2017;5(3):271-7. doi: 10.1007/s40139-017-0149-3. [PubMed: 29038745]. [PubMed Central: PMC5640269].
  • 3. Ghetti M, Topouzi H, Theocharidis G, Papa V, Williams G, Bondioli E, et al. Subpopulations of dermal skin fibroblasts secrete distinct extracellular matrix: implications for using skin substitutes in the clinic. Br J Dermatol. 2017. doi: 10.1111/bjd.16255. [PubMed: 29266210].
  • 4. Zhang Q, Wei F, Fong CC, Yu WK, Chen Y, Koon CM, et al. Transcriptional profiling of human skin fibroblast cell line Hs27 induced by herbal formula Astragali Radix and Rehmanniae Radix. J Ethnopharmacol. 2011;138(3):668-75. doi: 10.1016/j.jep.2011.08.080. [PubMed: 22075453].
  • 5. Yates CC, Hebda P, Wells A. Skin wound healing and scarring: fetal wounds and regenerative restitution. Birth Defects Res C Embryo Today. 2012;96(4):325-33. doi: 10.1002/bdrc.21024. [PubMed: 24203921]. [PubMed Central: PMC3967791].
  • 6. Li M, Zhao Y, Hao H, Han W, Fu X. Theoretical and practical aspects of using fetal fibroblasts for skin regeneration. Ageing Res Rev. 2017;36:32-41. doi: 10.1016/j.arr.2017.02.005. [PubMed: 28238941].
  • 7. Walraven M, Akershoek JJ, Beelen RH, Ulrich MM. In vitro cultured fetal fibroblasts have myofibroblast-associated characteristics and produce a fibrotic-like environment upon stimulation with TGF-beta1: Is there a thin line between fetal scarless healing and fibrosis? Arch Dermatol Res. 2017;309(2):111-21. doi: 10.1007/s00403-016-1710-3. [PubMed: 28004279].
  • 8. Hotchin NA, Zuliani T, Saiagh S, Knol AC, Esbelin J, Dreno B. Fetal Fibroblasts and Keratinocytes with Immunosuppressive Properties for Allogeneic Cell-Based Wound Therapy. PLoS ONE. 2013;8(7). e70408. doi: 10.1371/journal.pone.0070408.
  • 9. Lorenz HP, Whitby DJ, Longaker MT, Adzick NS. Fetal wound healing. The ontogeny of scar formation in the non-human primate. Ann Surg. 1993;217(4):391-6. [PubMed: 8466310]. [PubMed Central: PMC1242806].
  • 10. Lorenz HP, Longaker MT, Perkocha LA, Jennings RW, Harrison MR, Adzick NS. Scarless wound repair: a human fetal skin model. Development. 1992;114(1):253-9. [PubMed: 1576963].
  • 11. Longaker MT, Whitby DJ, Ferguson MW, Lorenz HP, Harrison MR, Adzick NS. Adult skin wounds in the fetal environment heal with scar formation. Ann Surg. 1994;219(1):65-72. [PubMed: 8297179]. [PubMed Central: PMC1243092].
  • 12. Rolfe KJ, Cambrey AD, Richardson J, Irvine LM, Grobbelaar AO, Linge C. Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors. BMC Dev Biol. 2007;7:124. doi: 10.1186/1471-213X-7-124. [PubMed: 17988375]. [PubMed Central: PMC2211318].
  • 13. Mizuno N, Shiba H, Ozeki Y, Mouri Y, Niitani M, Inui T, et al. Human autologous serum obtained using a completely closed bag system as a substitute for foetal calf serum in human mesenchymal stem cell cultures. Cell Biol Int. 2006;30(6):521-4. doi: 10.1016/j.cellbi.2006.01.010. [PubMed: 16616867].
  • 14. Pytlik R, Stehlik D, Soukup T, Kalbacova M, Rypacek F, Trc T, et al. The cultivation of human multipotent mesenchymal stromal cells in clinical grade medium for bone tissue engineering. Biomaterials. 2009;30(20):3415-27. doi: 10.1016/j.biomaterials.2009.03.001. [PubMed: 19362364].
  • 15. Unger C, Skottman H, Blomberg P, Dilber MS, Hovatta O. Good manufacturing practice and clinical-grade human embryonic stem cell lines. Hum Mol Genet. 2008;17(R1):R48-53. doi: 10.1093/hmg/ddn079. [PubMed: 18632697].
  • 16. Thirumala S, Goebel WS, Woods EJ. Clinical grade adult stem cell banking. Organogenesis. 2009;5(3):143-54. [PubMed: 20046678]. [PubMed Central: PMC2781095].
  • 17. Arjmand B, Goodarzi P, Falahzadeh K, Aghayan HR, Rahim F, Mohamadi-Jahani F, et al. GMP-Compliant Perinatal Tissue-Derived Stem Cells. In: Arjmand B, editor. Perinatal Tissue-Derived Stem Cells: Alternative Sources of Fetal Stem Cells. Switzerland: Springer; 2016. p. 189-213. doi: 10.1007/978-3-319-46410-7_9.
  • 18. Aghayan HR, Arjmand B, Burger SR. GMP Facilities for Clinical Cell Therapy Product Manufacturing: A Brief Review of Requirements and Design Considerations. In: Arjmand B, editor. Perinatal Tissue-Derived Stem Cells: Alternative Sources of Fetal Stem Cells. Switzerland: Springer; 2016. p. 215-27.
  • 19. Aghayan HR, Arjmand B, Norouzi-Javidan A, Saberi H, Soleimani M, Tavakoli SA, et al. Clinical grade cultivation of human Schwann cell, by the using of human autologous serum instead of fetal bovine serum and without growth factors. Cell Tissue Bank. 2012;13(2):281-5. doi: 10.1007/s10561-011-9250-8. [PubMed: 21484231].
  • 20. Bieback K, Kinzebach S, Karagianni M. Translating research into clinical scale manufacturing of mesenchymal stromal cells. Stem cells international. 2010;2010.
  • 21. Hirt-Burri N, Ramelet AA, Raffoul W, de Buys Roessingh A, Scaletta C, Pioletti D, et al. Biologicals and fetal cell therapy for wound and scar management. ISRN Dermatol. 2011;2011:549870. doi: 10.5402/2011/549870. [PubMed: 22363853]. [PubMed Central: PMC3262533].
  • 22. Takashima A. Establishment of fibroblast cultures. Curr protocol cell biol. 1998;(1):2.1. 1-2.1. 12.
  • 23. Halfon S, Abramov N, Grinblat B, Ginis I. Markers distinguishing mesenchymal stem cells from fibroblasts are downregulated with passaging. Stem Cells Dev. 2011;20(1):53-66. doi: 10.1089/scd.2010.0040. [PubMed: 20528146].
  • 24. Applegate LA, Scaletta C, Hirt-Burri N, Raffoul W, Pioletti D. Whole-cell bioprocessing of human fetal cells for tissue engineering of skin. Skin Pharmacol Physiol. 2009;22(2):63-73. doi: 10.1159/000178865. [PubMed: 19188754].
  • 25. De Buys Roessingh AS, Hohlfeld J, Scaletta C, Hirt-Burri N, Gerber S, Hohlfeld P, et al. Development, Characterization, and Use of a Fetal Skin Cell Bank for Tissue Engineering in Wound Healing. Cell Transplant. 2017;15(8-9):823-34. doi: 10.3727/000000006783981459.
  • 26. Hohlfeld J, de Buys Roessingh A, Hirt-Burri N, Chaubert P, Gerber S, Scaletta C, et al. Tissue engineered fetal skin constructs for paediatric burns. Lancet. 2005;366(9488):840-2. doi: 10.1016/s0140-6736(05)67107-3.
  • 27. Nodder S, Martin P. Wound healing in embryos: a review. Anat Embryol (Berl). 1997;195(3):215-28. [PubMed: 9084820].
  • 28. Shiraha H, Gupta K, Drabik K, Wells A. Aging fibroblasts present reduced epidermal growth factor (EGF) responsiveness due to preferential loss of EGF receptors. J Biol Chem. 2000;275(25):19343-51. doi: 10.1074/jbc.M000008200. [PubMed: 10764734].
  • 29. Prathalingam N, Ferguson L, Young L, Lietz G, Oldershaw R, Healy L, et al. Production and validation of a good manufacturing practice grade human fibroblast line for supporting human embryonic stem cell derivation and culture. Stem Cell Res Ther. 2012;3(2):12. doi: 10.1186/scrt103. [PubMed: 22472092]. [PubMed Central: PMC3392772].
  • 30. Yoon JH, Roh EY, Shin S, Jung NH, Song EY, Chang JY, et al. Comparison of explant-derived and enzymatic digestion-derived MSCs and the growth factors from Wharton's jelly. Biomed Res Int. 2013;2013:428726. doi: 10.1155/2013/428726. [PubMed: 23653895]. [PubMed Central: PMC3638666].
  • 31. Priya N, Sarcar S, Majumdar AS, SundarRaj S. Explant culture: a simple, reproducible, efficient and economic technique for isolation of mesenchymal stromal cells from human adipose tissue and lipoaspirate. J Tissue Eng Regen Med. 2014;8(9):706-16. doi: 10.1002/term.1569. [PubMed: 22837175].
  • 32. Gittel C, Brehm W, Burk J, Juelke H, Staszyk C, Ribitsch I. Isolation of equine multipotent mesenchymal stromal cells by enzymatic tissue digestion or explant technique: comparison of cellular properties. BMC Vet Res. 2013;9:221. doi: 10.1186/1746-6148-9-221. [PubMed: 24168625]. [PubMed Central: PMC4228449].
  • 33. Tannenbaum SE, Turetsky TT, Singer O, Aizenman E, Kirshberg S, Ilouz N, et al. Derivation of xeno-free and GMP-grade human embryonic stem cells--platforms for future clinical applications. PLoS One. 2012;7(6). e35325. doi: 10.1371/journal.pone.0035325. [PubMed: 22745653]. [PubMed Central: PMC3380026].
  • 34. Burger SR. Current regulatory issues in cell and tissue therapy. Cytotherapy. 2003;5(4):289-98. doi: 10.1080/14653240310002324. [PubMed: 12944234].
  • 35. Larijani B, Aghayan HR, Goodarzi P, Arjmand B. GMP-grade human fetal liver-derived mesenchymal stem cells for clinical transplantation. Methods Mol Biol. 2015;1283:123-36. doi: 10.1007/7651_2014_101. [PubMed: 25092054].
  • 36. Aghayan HR, Goodarzi P, Arjmand B. GMP-compliant human adipose tissue-derived mesenchymal stem cells for cellular therapy. In: Turksen K, editor. Stem Cells and Good Manufacturing Practices. Springer; 2014. p. 93-107.
  • 37. Brooke G, Rossetti T, Pelekanos R, Ilic N, Murray P, Hancock S, et al. Manufacturing of human placenta-derived mesenchymal stem cells for clinical trials. Br J Haematol. 2009;144(4):571-9. doi: 10.1111/j.1365-2141.2008.07492.x. [PubMed: 19077161].
  • 38. Bieback K, Schallmoser K, Kluter H, Strunk D. Clinical Protocols for the Isolation and Expansion of Mesenchymal Stromal Cells. Transfus Med Hemother. 2008;35(4):286-94. doi: 10.1159/000141567. [PubMed: 21512644]. [PubMed Central: PMC3076361].
  • 39. Arjmand B, Aghayan HR. Cell manufacturing for clinical applications. Stem Cells. 2014;32(9):2557-8. doi: 10.1002/stem.1751. [PubMed: 24891087].

Featured Image:

Creative Commons License Except where otherwise noted, this work is licensed under Creative Commons Attribution Non Commercial 4.0 International License .

Search Relations:



Create Citiation Alert
via Google Reader

Readers' Comments