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The Role of Stem Cells Derived From the Mesenchyme of the Umbilical Cord in Reducing Immunosuppressive Drug Doses Used in Allogenic Transplantations

Annals of Plastic Surgery · Aralık 2022

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YÖKSİS Kayıtları
The Role of Stem Cells Derived From the Mesenchyme of the Umbilical Cord in Reducing Immunosuppressive Drug Doses Used in Allogenic Transplantations
Annals of Plastic Surgery · 2022 SCI-Expanded
DOÇENT İSMAİL HARMANKAYA →

Makale Bilgileri

DergiAnnals of Plastic Surgery
Yayın TarihiAralık 2022
Cilt / Sayfa89 · 684-693
Özet Background This study evaluated the potential of Wharton's jelly mesenchymal stem cells with high tolerogenic properties in reducing immunosuppressive dosage and related adverse effects. Methods A 4- to 6-week-old, 30-40 g weight, male inbred CD57BL/6 mice were used as skin allograft donors, whereas Balb/c mice with similar characteristics were used as recipients. Wharton's jelly stem cells were obtained from a commercial kit sourced from human umbilical cord. Skin allografts were performed from CD57Bl6 to Balb/c mice (day 0). Group 1 (control) received no treatment. Group 2 received 15 mg/kg cyclosporin A on days 0 to 30. Group 3 received 5.7 × 106 and 10.3 × 106 cell/kg Wharton's jelly stem cells on days 0 and 3, respectively. Groups 4, 5, and 6 received a combination of 15, 10, and 5 mg/kg per day cyclosporine A (days 0 to 30) with the same stem cell dose with group 3, respectively. Graft rejection was evaluated with digital photography and thermal imaging, histopathology (Banff grading, epithelialization scores, dermoepidermal dissociation), immunochemistry (Ki-67 and Bcl-2), and biochemical methods (interleukin 10, interleukin 2, interferon γ, tumor necrosis factor α) (day 10). Cumulative adverse effects of cyclosporin A occurring in the groups were revealed by histopathological evaluation of kidney and liver (a modified semiquantitative method of infiltration of inflammatory cells around the portal area and lobular region in liver; modification of the Banff rating of proximal tubules and hypertrophia of juxtaglomerular apparatus cells in kidney) (day 30). Results There was no rejection in groups 2, 4, and 5 until the end of study. These were statistically different versus groups 1 (day 10 ± 0.71), 3 (day 11 ± 0.82), and 6 (day 11 ± 0.58) (all P's < 0.05). Groups 4 and 5 have exhibited statistically similar findings in histopathological (4 epithelization score: 3.7 ± 1.3; 5 epithelization score: 3.5 ± 0.5; 4 Banff grading score: 0.8 ± 0.6; 5 Banff grading score: 1.0 ± 0.5; both P's = 1.00), immunohistochemical (4 Bcl-2 score: 3.5 ± 0.5, P = 0.618; 5 Bcl-2 score: 3.4 ± 0.5, P = 1.00; 4 Ki-67 score: 3.7 ± 0.4, P = 1.00; 5 Ki-67 score: 3.5 ± 0.5, both P's = 1.00), and levels of cytokines (both P's = 1.00) versus group 2. Adverse effects on kidneys and liver were lowest and statistically similar in groups 3, 5, and 6 (all P's = 00) versus group 1. Conclusions Wharton's jelly mesenchymal stem cells alter bioavailability of cyclosporine, albeit at much lower doses and with fewer systemic adverse effects.

Yazarlar (6)

1
Seyda Guray Evin
2
Mustafa Sutcu
3
Tahsin Murad Aktan
4
Selcuk Duman
5
İsmail Harmankaya
6
Sedat Abusoglu
ORCID: 0000-0002-2984-0527

Anahtar Kelimeler

adverse effects of immunosuppressant allotransplantation Wharton's jelly mesenchymal stem cell

Kurumlar

Goztepe Prof. Dr. Suleyman Yalcin City Hospital
Istanbul Turkey
Necmettin Erbakan Üniversitesi
Meram Turkey
Selçuk Tip Fakültesi
Konya Turkey