Farklı doku kökenli mezenkimal kök hücreler ve propolisin diyabetik sıçanlarda oluşturulan deneysel yanık modelinde kullanılması
Küçük Resim Yok
Tarih
2016
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Diabetes mellitus (DM), kronik metabolik bir hastalıktır ve özellikle mikrovaskuler komplikasyonlara bağlı kronik yara iyileşmesi problemleri ve buna bağlı oluşan ampütasyonların başlıca nedenlerinden biridir. Diyabetik hastalarda yanık yarası oluştuğunda, enfeksiyon ve ampütasyon gibi önemli komplikasyonların gelişme riski oldukça yüksektir. Bu nedenle diyabetik olguların yanık ve travmalara bağlı yara oluşumu söz konusu olduğunda, hospitalizasyon süresini azaltabilmek ve hastaların hızla iyileştirilmelerini sağlamak amacıyla güncel rejeneratif tıp yaklaşımlarının deneysel diyabet modelleri kullanılarak oluşturulan yanık modelleri üzerinde etkilerinin incelenerek araştırılmasında yarar vardır. Mezenkimal Kök Hücreler (MSCs), yara iyileşmesinin her üç aşamasında da rol oynamaktadır. MSC ayrıca, yara iyileşmesinin enflamatuar aşamasında ve kronik yara durumuna gerilemesini önlemede de etkilidir. MSC'nin en önemli özelliklerinden biri doğrudan enflamatuar yanıtın daha hafif bir düzeyde devam etmesini sağlayacak şekilde etkilemektir. Propolis, dermatolojinin yara iyileşmesi, yanıklar ve eksternal ülserlerin tedavisi, iyileşme zamanının azaltılması, yara kontraksiyonunun arttırılması ve doku tamirinin hızlandırılması gibi birçok alt alanında yaygın olarak kullanılmaktadır. Bu çalışmada, sıçanların yağ dokusu ve kemik iliği eksize edilip, bu dokulardan mezenkimal kök hücreleri sırasıyla, Adipoz doku kökenli MSCs (AD-SCs) ve kemik iliği kökenli MSCs (BM-SCs), ayrıştırılarak çoğaltıldı. STZ-diyabetik sıçanlarla oluşturulan propolis uygulanan/uygulanmayan gruplara elde edilen hücreler enjekte edildi. Bu uygulamaların sekonder yanık yara iyileşmesindeki etkisi, sıçanların sırtlarından uygulamayı takip eden 3., 7., 10. ve 14. günlerde biyopsiyle doku örneklerinde çalışılan erken ve geç dönem yara iyileşmesi markerlarının immunohistokimyasal verileri incelenerek değerlendirilmiştir. AD-SCs ve BM-SCs uygulanan gruplarda, kontrol gruba göre büyüme faktörleri (epidermal büyüme faktörü (EGF), dönüştürücü büyüme faktörü (TGF-?1), fibroblast büyüme faktörü-2 (FGF-2) ve vasküler endoteliyal büyüme faktörü (VEGF)) ve kollajen-1 için in situ ekspresyon artışı göründü. Monosit kemoatraktan protein-1 (MCP-1) miktarında ise zamana bağlı değişen bir azalma gözlendi. Propolis uygulanan grupta ise büyüme faktörlerinden sadece FGF-2 ve VEGF de artış gözlenirken, kollajen-1 artışı ve MCP-1 düzeyindeki azalma da diğer gruplardakine benzer şekilde gözlendi. Tüm gruplardan elde edilen sonuçlar değerlendirildiğinde, Mezenkimal kök hücrelerin lokal propolis tedavisi ile beraber verildiği gruplarda iyileşme hızı en iyi gözlenirken, farklı doku kökenlerinden gelen mezenkimal kök hücrelerin etki açısından bir farklılığa yol açmadığı da gözlenmiştir. Yara iyileşmesinde uygulama açısından, yağ dokusu da kemik iliği kadar efektif ve iyi sonuç veren bir kök hücre kaynağı olarak değerlendirilebilir. Ayrıca propolisin yara tedavisinde adjuvan olarak kullanılmasının yarar sağlayabileceği de çalışma sonuçları ile gösterilmiştir. Anahtar Kelimeler: Yara İyileşmesi, Yanık Yara, Mezenkimal Kök Hücreler, Propolis, Diyabet, Sıçan?
Diabetes mellitus (DM) is a chronic metabolic disease and is one of the major causes of chronic wound healing problems and related amputations which are particularly due to microvascular complications. When diabetic patients develop a burn wound, the risk of occurrence of important complications such as infections and amputations are rather high. Therefore, if the formation of wounds due to burns and trauma in diabetic cases is the concern, it is useful to evaluate the effects of current regenerative medical approaches on burn models created by use of experimental diabetic models in order to reduce the duration of hospitalization and to provide rapid treatments to these patients. MSCs play a role in all three phases of the wound healing process. In addition, they are effective in inflammatory phase of the wound healing as well as they are essential for prevention of a regression through a chronic wound phase. One of the paramount effects of MSCs is the ability to directly affect the inflammatory response to progress in a moderate level. Propolis is widely used in various sub-fields of dermatology such as wound healing, treatment of external ulcerations and burns, enhancement of wound contractions and acceleration of tissue repair. In this study, rat adipose tissue and bone marrow were excised and MSCs (AD-SCs and BM-SCs, respectively) were isolated and amplified. Obtained cells were injected to the groups of STZ-diabetic rats which are treated or non-treated with propolis. The effect of these applications in secondary burn wound healing was evaluated by examining the immunohistochemical data obtained for the early and late wound healing markers studied on biopsy samples that were taken from dorsal side of the rats on 3rd, 7th, 10th and 14th days after the treatments. Increase of in situ expression for Collagen-1 and an elevated expression profile of the studied growth factors (Epidermal growth factor (EGF), Transforming growth factor beta 1 (TGF-?1), fibroblast growth factor-2 (FGF-2) and Vascular endothelial growth factor (VEGF)) were observed in both AD-SCs-treated and BM-SCs-treated groups compared to control animals. A time-dependent decrease in the amount of monocyte chemotactic protein-1 (MCP-1) was also observed. Among the growth factors evaluated, only an increase in expression levels of FGF-2 and VEGF was seen in the animal groups treated with propolis where it was also observed that the increase in expression of Collagen-1 and the decrease in expression of MCP-1 are similar to other treatment groups. When all the results obtained from all the groups were evaluated, the best progress of wound healing was observed in the group treated both with local application of propolis and mesenchymal stem cells. Moreover, the application of mesenchymal stem cells from different tissue of origins did not result in a difference with respect to their effectiveness during wound healing. In terms of medical approaches for wound healing, adipose tissue could be regarded as effective as the bone marrow which gives good application outcomes. At the same time, it was also proven with these results that the use of propolis as an adjuvant substance in treatments for wound healing could be beneficial. Keywords: Wound Healing, Burn Wound, Mesenchymal Stem Cell, Propolis, Diabetes, Rats
Diabetes mellitus (DM) is a chronic metabolic disease and is one of the major causes of chronic wound healing problems and related amputations which are particularly due to microvascular complications. When diabetic patients develop a burn wound, the risk of occurrence of important complications such as infections and amputations are rather high. Therefore, if the formation of wounds due to burns and trauma in diabetic cases is the concern, it is useful to evaluate the effects of current regenerative medical approaches on burn models created by use of experimental diabetic models in order to reduce the duration of hospitalization and to provide rapid treatments to these patients. MSCs play a role in all three phases of the wound healing process. In addition, they are effective in inflammatory phase of the wound healing as well as they are essential for prevention of a regression through a chronic wound phase. One of the paramount effects of MSCs is the ability to directly affect the inflammatory response to progress in a moderate level. Propolis is widely used in various sub-fields of dermatology such as wound healing, treatment of external ulcerations and burns, enhancement of wound contractions and acceleration of tissue repair. In this study, rat adipose tissue and bone marrow were excised and MSCs (AD-SCs and BM-SCs, respectively) were isolated and amplified. Obtained cells were injected to the groups of STZ-diabetic rats which are treated or non-treated with propolis. The effect of these applications in secondary burn wound healing was evaluated by examining the immunohistochemical data obtained for the early and late wound healing markers studied on biopsy samples that were taken from dorsal side of the rats on 3rd, 7th, 10th and 14th days after the treatments. Increase of in situ expression for Collagen-1 and an elevated expression profile of the studied growth factors (Epidermal growth factor (EGF), Transforming growth factor beta 1 (TGF-?1), fibroblast growth factor-2 (FGF-2) and Vascular endothelial growth factor (VEGF)) were observed in both AD-SCs-treated and BM-SCs-treated groups compared to control animals. A time-dependent decrease in the amount of monocyte chemotactic protein-1 (MCP-1) was also observed. Among the growth factors evaluated, only an increase in expression levels of FGF-2 and VEGF was seen in the animal groups treated with propolis where it was also observed that the increase in expression of Collagen-1 and the decrease in expression of MCP-1 are similar to other treatment groups. When all the results obtained from all the groups were evaluated, the best progress of wound healing was observed in the group treated both with local application of propolis and mesenchymal stem cells. Moreover, the application of mesenchymal stem cells from different tissue of origins did not result in a difference with respect to their effectiveness during wound healing. In terms of medical approaches for wound healing, adipose tissue could be regarded as effective as the bone marrow which gives good application outcomes. At the same time, it was also proven with these results that the use of propolis as an adjuvant substance in treatments for wound healing could be beneficial. Keywords: Wound Healing, Burn Wound, Mesenchymal Stem Cell, Propolis, Diabetes, Rats
Açıklama
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Anahtar Kelimeler
Moleküler Tıp, Molecular Medicine
