Radyoterapi Almış Ratlarda Mezenkimal Kök Hücre Tedavisinin Kolon Anastomozuna Etkileri

Abstract

Amaç: Kolorektal kanserler dünya genelinde en sık görülen üçüncü malignitedir. Rektum kanserinde neoadjuvan radyoterapi (nRT) lokal kontrolü artırmakla birlikte anastomoz kaçağı riskini yükseltmektedir. Mezenkimal kök hücrelerin (MKH) yara iyileşmesini destekleyici etkileri olduğu bilinmektedir. Bu çalışmada, nRT sonrası sıçanlarda kolon anastomoz iyileşmesi üzerine MKH tedavisinin etkilerinin değerlendirilmesi amaçlandı. Gereç ve Yöntemler: Elli beş Wistar Albino sıçan dört gruba ayrıldı: kontrol, nRT, nRT + lokal MKH ve nRT + lokal + intraperitoneal MKH. nRT gruplarına ameliyat öncesinde tek doz 12 Gy radyoterapi uygulandı. Her bir sıçana anastomoz hattına lokal olarak yaklaşık 1 × 106 adipoz doku kökenli mezenkimal kök hücre 0,1 mL hacimde uygulandı; nRT + lokal MKH grubunda dozun tamamı anastomoz hattına lokal olarak verilirken, nRT + lokal + intraperitoneal MKH grubunda dozun yarısı lokal, kalan yarısı intraperitoneal olarak uygulandı. Anastomoz iyileşmesi barsak patlama basıncı (BPB), histopatolojik ve biyokimyasal incelemelerle değerlendirildi. Bulgular: Radyoterapi uygulanan gruplarda anlamlı kilo kaybı ve daha düşük BPB değerleri izlendi. Kök hücre uygulanan gruplarda BPB değerleri nRT grubuna kıyasla daha yüksek olmakla birlikte bu fark istatistiksel olarak anlamlı değildi. Histopatolojik ve biyokimyasal parametreler açısından gruplar arasında anlamlı fark saptanmadı. Ancak yalnızca nRT grubunda anastomoz hattında makroskopik ayrışma gözlenirken, kök hücre uygulanan gruplarda makroskopik ayrışma izlenmedi. İmmunfloresan incelemede, anastomoz hattında farklılaşmış kök hücrelerin varlığı gösterildi. Sonuç: Mezenkimal kök hücre tedavisi, biyokimyasal ve histopatolojik parametrelerde istatistiksel olarak anlamlı bir iyileşme sağlamamakla birlikte, makroskopik anastomoz ayrışmasının görülmemesi ve daha yüksek patlama basıncı eğilimi göstermesi nedeniyle, neoadjuvan radyoterapi sonrası lokal anastomoz iyileşmesini destekleyici potansiyel bir etkiye sahip olabilir. Bu bulgular, mezenkimal kök hücrelerin adjuvan bir tedavi yaklaşımı olarak ileri deneysel ve klinik çalışmalarla değerlendirilmesi gerektiğini düşündürmektedir.

Keywords

• Kolorektal neoplaziler
• radyoterapi
• anastomoz kaçağı
• mezenkimal kök hücreler
• yara iyileşmesi.

Supporting Institution

Başkent Üniversitesi Araştırma Fonunca desteklenmiştir.

Project Number

DA 22/01

Ethical Statement

Bu çalışma Başkent Üniversitesi Hayvan Deneyleri Etik Kurulu tarafından onaylanmıştır

THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY

Abstract

Objective: Colorectal cancer is the third most common malignancy worldwide. Although neoadjuvant radiotherapy (nRT) improves local control in rectal cancer, it increases the risk of anastomotic leakage. Mesenchymal stem cells (MSCs) have been shown to support wound healing. This study aimed to evaluate the effects of MSC therapy on anastomotic healing after nRT in a rat model. Material and Methods: Fifty-five Wistar Albino rats were allocated into four groups: control, nRT, nRT + local MSCs, and nRT + local + intraperitoneal MSCs. A single 12 Gy dose of radiotherapy was administered preoperatively to the nRT groups. Each rat received a total of approximately 1 × 10⁶ adipose-derived MSCs in 0.1 mL; in the local MSC group, the entire dose was administered subserosally to the anastomotic site, whereas in the combined group, half of the dose was administered locally and the remaining half intraperitoneally. Anastomotic healing was assessed using burst pressure (BP), histopathological evaluation, and biochemical analyses. Results: Rats receiving nRT demonstrated significant weight loss and lower BP values. In the MSC-treated groups, BP values were higher compared with the nRT-only group, although these differences did not reach statistical significance. Histopathological and biochemical parameters did not differ significantly among the groups. Notably, gross anastomotic separation was observed only in the nRT-only group, whereas no such separation was detected in the MSC-treated groups. Fluorescent imaging confirmed the presence of differentiated MSCs at the anastomotic site. Conclusion: Although MSC therapy did not result in statistically significant improvements in biochemical or histopathological parameters, the absence of gross anastomotic separation and the tendency toward higher burst pressure values suggest that MSCs may support local anastomotic healing after neoadjuvant radiotherapy. These findings indicate a potential role for MSC therapy as an adjunctive strategy, warranting further experimental and clinical investigation.

Keywords

• Colorectal neoplasms
• radiotherapy
• anastomotic leak
• mesenchymal stem cells
• wound healing.

Supporting Institution

This study supported by Baskent University Research Fund.

Project Number

DA 22/01

Ethical Statement

This study was approved by Baskent University Ethical Committee for Experimental Resarch on Animals

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