Toxicological Analysis of a New Fibrin-Derived Dermal Scaffold (Dermoturk); Acellular and Combined with Stem Cells Forms

Year 2024, Volume: 18 Issue: 2, 130 - 139, 18.03.2024

Emrah Şenel , Sabri Demir , Aysun Gökce , Murat Alper , Mesut Akyol , Fatma Eyüboğlu , Ercüment Ovalı

https://doi.org/10.12956/tchd.1405903

Abstract

Objective: We aimed to reveal the toxicological analysis of the newly developed fibrin-derived scaffold forms (DermoTurk) before human studies.
Material and Methods: 42 male Albino Wistar rats were used. Two of them were used to produce mesenchymal and epidermal stem cells. Forty rats were divided into five groups, each consisting of 8 rats; the acellular scaffold applied group as Group-1, the mesenchymal stem cells added scaffold used group as Group-2, the MSCs and epidermal stem cells-added scaffold applied group as Group-3, MSCs- and epidermal stem cells-added scaffold applied outbred group as Group-4 and control as Group-5. The changing of laboratory tests in the groups was evaluated five days before application and on the 7th and 40th days. After the autopsy performed on the 40th day of the study, rats’ organs and scaffold implanted skin area were evaluated histologically. All the results of the groups were compared. SPSS 22.0 was used for analyses. P <0.05 was accepted as statistically significant.
Results: There were no differences between the groups in terms of laboratory results. Histologically, a mild-grade foreign body reaction against the DermoTurk was found in all groups; this reaction was less in groups 3 and 4 with the richest stem cells.
Conclusion: This study revealed that DermoTurk is safe in rats. It could be an important alternative to skin substitutes, with stem cells or alone. Human studies for clinical efficacy should be carried out.

Keywords

Mesenchymal stem cell, epidermal stem cell, tissuue engineering, burn, fibrin-derived dermal scaffold

Fibrinden Türetilmiş Yeni Bir Dermal matriksin (DermoTurk) Aselüler ve Kök Hücreler ile Kombine Formlarının Toksikolojik Analizi

Abstract

Amaç: Bu çalışmamızda yeni geliştirdiğimiz fibrinden türetilmiş dermal matriksin (DermoTurk) değişik formlarının insan çalışmalarından önce yaptığımız toksikoloji testlerinin sonuçlarını paylaşmayı amaçladık.
Gereç ve Yöntemler: Çalışmada 42 adet erkek Albino-Wistar rat kullanıldı. Bunlardan ikisi mezenkimal ve epidermal kök hücre üretmek için kullanıldı. Kırk tane rat ise her biri 8 denekten oluşan beş gruba ayrıldı; aselüler matriks uygulanan grup (Grup-1), fibrin matriks ile mezenkimal kök hücre (MKH) uygulanan grup (Grup-2), fibrin matriks ile MKH'ler ve epidermal kök hücrelerin (EKH) uygulandığı inbread grup (Grup-3), fibrin matrilks ile MKH'ler ve EKH'lerin uygulandığı outbread grup (Grup-4), kontrol ise Grup-5 olarak belirlendi. Gruplardaki laboratuvar testlerinin sonuçları uygulamadan beş gün önce ve uygulamanın 7. ve 40. günlerinde değerlendirildi. Çalışmanın 40. gününde yapılan otopsinin ardından deneklerin organları ve fibrin matriks implante edilen cilt alanı histolojik olarak değerlendirildi. Grupların tüm sonuçları karşılaştırıldı. İstatistiksel analiz SPSS 22.0 ile yapıldı. P<0,05 istatistiksel olarak anlamlı kabul edildi.
Bulgular: Laboratuvar sonuçları açısından gruplar arasında fark yoktu. Histolojik olarak tüm gruplarda DermoTurk'e karşı hafif derecede yabancı cisim reaksiyonu saptandı; bu reaksiyon kök hücrelerin bulunduğu 3. ve 4. gruplarda daha azdı.
Sonuç: Çalışmamız fibrinden türetilen DermoTurk'ün ratlarda güvenli olduğunu göstermiştir. Bu matriks kök hücrelerle veya tek başına diğer deri benzerlerine önemli bir alternatif olabilir. Klinik etkinliliğin gösterilmesi için insan çalışmaları yapılmalıdır.

Keywords

Mezenkimal kök hücreler, epidermal kök hücreler, doku mühendisliği, yanık, fibrinden türetilmiş dermal matriks

References

• 1. Huang YZ, Lu GZ, Zhao HS, Liu LJ, Jin J, Wu YF, et al. Clinical features and mortality-related factors of extensive burns among young adults: the Kunshan disaster experience. Ann Transl Med 2020;8:1053.
• 2. Smolle C, Cambiaso-Daniel J, Forbes AA, Wurzer P, Hundeshagen G, Branski LK, et al. Recent trends in burn epidemiology worldwide: A systematic review. Burns 2017;43:249-57.
• 3. Strong AL, Neumeister MW, Levi B. Stem Cells and Tissue Engineering: Regeneration of the Skin and Its Contents. Clin Plast Surg 2017;44:635-50.
• 4. Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell 1975;6:331-43.
• 5. Elloso M, Kambli A, Aijaz A, van de Kamp A, Jeschke MG. Burns in the Elderly: Potential Role of Stem Cells. Int J Mol Sci 2020;21:4604.
• 6. Wang M, Yuan Q, Xie L. Mesenchymal Stem Cell-Based Immunomodulation: Properties and Clinical Application. Stem Cells Int 2018;2018:3057624.
• 7. Caliari-Oliveira C, Yaochite JN, Ramalho LN, Palma PV, Carlos D, Cunha Fde Q, et al. Xenogeneic Mesenchymal Stromal Cells Improve Wound Healing and Modulate the Immune Response in an Extensive Burn Model. Cell Transplant 2016;25:201-15.
• 8. de Kanter AJ, Jongsma KR, Verhaar MC, Bredenoord AL. The Ethical Implications of Tissue Engineering for Regenerative Purposes: A Systematic Review. Tissue Eng Part B Rev 2023;29:167-87.
• 9. McHeik JN, Barrault C, Levard G, Morel F, Bernard FX, Lecron JC. Epidermal healing in burns: autologous keratinocyte transplantation as a standard procedure: update and perspective. Plast Reconstr Surg Glob Open 2014;2:e218.
• 10. Chen X, Laurent A, Liao Z, Jaccoud S, Abdel-Sayed P, Flahaut M, et al. Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care. Pharmaceutics 2023;15:2334.
• 11. Kang L, Zhou Y, Chen X, Yue Z, Liu X, Baker C, et al. Fabrication and Characterization of an Electro-Compacted Collagen/Elastin/Hyaluronic Acid Sheet as a Potential Skin Scaffold. Macromol Biosci 2023;23:e2300220.
• 12. Sclafani AP, McCormick SA. Induction of dermal collagenesis, angiogenesis, and adipogenesis in human skin by injection of platelet-rich fibrin matrix. Archives of facial plastic surgery 2012;14:132-6.
• 13. Sclafani AP, Azzi J. Platelet preparations for use in facial rejuvenation and wound healing: a critical review of current literature. Aesthetic plastic surgery 2015;39:495-505.
• 14. O’Connor NE MJ, Banks-Schlegel S, Kehinde O, Green H. Grafting of burns with cultured epithelium prepared from autologous epidermal cells. Lancet 1981;1:75-8.
• 15. Domaszewska-Szostek AP, Krzyżanowska MO, Czarnecka AM, Siemionow M. Local Treatment of Burns with Cell-Based Therapies Tested in Clinical Studies. J Clin Med 2021;10:396.
• 16. Frese L, Dijkman PE, Hoerstrup SP. Adipose tissue-derived stem cells in regenerative medicine. Transfus Med Hemother 2016;43:268-74.
• 17. Gupta S, Mohapatra DP, Chittoria RK, Subbarayan E, Reddy SK, Chavan V, et al. Human Skin Allograft: Is it a Viable Option in Management of Burn Patients? J Cutan Aesthet Surg 2019;12:132-5.
• 18. Sclafani AP. Platelet-rich fibrin matrix for improvement of deep nasolabial folds. J Cosmet Dermatol 2010;9:66-71.
• 19. Sclafani AP. Safety, efficacy, and utility of platelet-rich fibrin matrix in facial plastic surgery. Arch Facial Plast Surg 2011;13:247-51.
• 20. Mansour RN, Hasanzadeh E, Abasi M, Gholipourmalekabadi M, Mellati A, Enderami SE. The Effect of Fetal Bovine Acellular Dermal Matrix Seeded with Wharton's Jelly Mesenchymal Stem Cells for Healing Full-Thickness Skin Wounds. Genes (Basel) 2023;14:909.
• 21. Gentile P, De Angelis B, Pasin M, Cervelli G, Curcio CB, Floris M, et al. Adipose-derived stromal vascular fraction cells and platelet-rich plasma: basic and clinical evaluation for cell-based therapies in patients with scars on the face. J Craniofac Surg 2014;25:267-72.
• 22. Pellegrini G, Rama P, Matuska S, Lambiase A, Bonini S, Pocobelli A, et al. Biological parameters determining the clinical outcome of autologous cultures of limbal stem cells. Regen Med 2013;8:553-67.
• 23. Feng C, Chen Q, Fan M, Guo J, Liu Y, Ji T, et al. Platelet-derived microparticles promote phagocytosis of oxidized low-density lipoprotein by macrophages, potentially enhancing foam cell formation. Ann Transl Med 2019;7:477.
• 24. Maguire G, Friedman P. Systems biology approach to developing S(2)RM-based "systems therapeutics" and naturally induced pluripotent stem cells. World J Stem Cells 2015;7:745-56.
• 25. Wu T, Liu Y, Wang B, Li G. The roles of mesenchymal stem cells in tissue repair and disease modification. Curr Stem Cell Res Ther 2014;9:424-31.
• 26. Pourjabbar B, Shams F, Moghadam M, Ahani-Nahayati M, Azari A, Sefat F, et al. Recent Emerging Trend in Stem Cell Therapy Risk Factors. Curr Stem Cell Res Ther 2023;18:1076-89.