The effect of mesenchymal stem cells derived from different sources on diabetic wound healing

Öz

Purpose: It is unclear whether the tissue source of mesenchymal stem cells (MSCs) influences their activity in diabetic wounds. This study aimed to compare the effects of dental pulp–derived and adipose tissue–derived MSCs on wound healing and on the cutaneous expression of tumor necrosis factor-α (TNF-α), interleukin (IL)-1, IL-6, and IL-10 in streptozotocin (STZ)-induced diabetic rats. To compare the effects of dental pulp–derived and adipose tissue–derived MSCs on diabetic wound healing and on the cutaneous expression of TNF-α, IL-1, IL-6, and IL-10 in a streptozotocin (STZ)-induced diabetic rat model. Materials and methods: Twenty-four male rats were allocated to four groups (n=6 each): non-diabetic control, diabetic control, and diabetic wounds treated with dental pulp–derived or adipose tissue–derived MSCs. Diabetes was induced with STZ (55 mg/kg, intraperitoneally). A 5 mm full-thickness wound was created, and 1×10⁶ MSCs were applied topically in the treatment groups. On day 10, skin sections were evaluated by hematoxylin–eosin and Masson's trichrome staining, and cytokine expression was scored immunohistochemically using the H-score. Results: Wound diameter did not differ significantly between the non-diabetic control and the MSC-treated groups, whereas the diabetic control showed significantly larger wounds. Histologically, both MSC-treated groups showed a thicker, better-organized epidermis and denser dermal collagen than the diabetic control. Compared with the diabetic control, both MSC-treated groups showed significantly lower IL-1 and IL-6 expression and higher IL-10 expression, whereas TNF-α expression did not change significantly. No significant differences were observed between the dental pulp– and adipose tissue–derived MSC groups for any marker except IL-10, which was higher in the adipose tissue–derived MSC group. Conclusion: Topical application of dental pulp– or adipose tissue–derived MSCs supported diabetic wound healing through an anti-inflammatory shift characterized by lower IL-1 and IL-6 and higher IL-10 expression, without significantly affecting TNF-α.

Anahtar Kelimeler

• Mesenchymal stem cells
• diabetes mellitus
• wound healing
• immunohistochemistry

Farklı kaynaklardan elde edilen mezenkimal kök hücrelerin diyabetik yara iyileşmesine etkisi

Öz

Amaç: Bozulmuş yara iyileşmesi diabetes mellitusun önemli bir komplikasyonudur ve mezenkimal kök hücreler (MKH'ler), düşük immünojeniteye sahip rasyonel bir tedavi seçeneği olarak öne çıkmaktadır. MKH'lerin doku kaynağının, diyabetik yaralardaki onarıcı ve immünomodülatör aktivitelerini etkileyip etkilemediği henüz tam olarak aydınlatılamamıştır. Streptozotosin (STZ) ile diyabet oluşturulan bir sıçan modelinde, diş pulpası kaynaklı ve yağ dokusu kaynaklı MKH'lerin diyabetik yara iyileşmesi üzerindeki etkilerini ve kutanöz TNF-α, IL-1, IL-6 ve IL-10 ekspresyonu üzerindeki etkilerini karşılaştırmak amaçlanmıştır. Streptozotosin (STZ) ile diyabet oluşturulan bir sıçan modelinde, diş pulpası kaynaklı ve yağ dokusu kaynaklı MKH'lerin diyabetik yara iyileşmesi üzerindeki etkilerini ve kutanöz TNF-α, IL-1, IL-6 ve IL-10 ekspresyonu üzerindeki etkilerini karşılaştırmak amaçlanmıştır. Gereç ve yöntem: Yirmi dört erkek sıçan dört gruba ayrıldı (her grupta n=6): diyabetik olmayan kontrol, diyabetik kontrol ve diş pulpası kaynaklı veya yağ dokusu kaynaklı MKH uygulanan diyabetik yara grupları. Diyabet, STZ (55 mg/kg, intraperitoneal) ile oluşturuldu. Beş mm çapında tam kat yara açıldı ve tedavi gruplarına topikal olarak 1×10⁶ MKH uygulandı. Onuncu günde deri kesitleri hematoksilen-eozin ve Masson trikrom boyamalarıyla değerlendirildi; sitokin ekspresyonu immünohistokimyasal olarak H-skoru ile puanlandı. Bulgular: Yara çapı, diyabetik olmayan kontrol grubu ile MKH uygulanan gruplar arasında anlamlı farklılık göstermezken, diyabetik kontrol grubunda yaralar anlamlı olarak daha büyüktü. Histolojik olarak, MKH uygulanan her iki grupta da diyabetik kontrole kıyasla daha kalın ve daha düzenli bir epidermis ile daha yoğun dermal kollajen izlendi. Diyabetik kontrol ile karşılaştırıldığında, MKH uygulanan her iki grupta IL-1 ve IL-6 ekspresyonu anlamlı olarak daha düşük, IL-10 ekspresyonu ise daha yüksekti; TNF-α ekspresyonunda anlamlı değişiklik saptanmadı. Diş pulpası ve yağ dokusu kaynaklı MKH grupları arasında IL-10 dışındaki hiçbir belirteç açısından anlamlı fark gözlenmedi; IL-10 yağ dokusu kaynaklı MKH grubunda daha yüksekti. Sonuç: Diş pulpası veya yağ dokusu kaynaklı MKH’lerin topikal uygulanması diyabetik yara iyileşmesini destekledi; buna IL-1 ve IL-6 ekspresyonunda azalma ile IL-10 ekspresyonunda artış eşlik ederken TNF-α'da anlamlı değişiklik olmadı. İki kaynak, yağ dokusu kaynaklı MKH’lerde daha yüksek olan IL-10 ekspresyonu dışında benzer sonuç verdi

Anahtar Kelimeler

• Mezenkimal kök hücreler
• diabetes mellitus
• yara iyileşmesi
• immünohistokimya

Kaynakça

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