kırıkkale üni tıp derg The Journal of Kırıkkale University Faculty of Medicine 2148-9645 Kırıkkale Üniversitesi 10.24938/kutfd.1804010 Health Care Administration Sağlık Kurumları Yönetimi Radyoterapi Almış Ratlarda Mezenkimal Kök Hücre Tedavisinin Kolon Anastomozuna Etkileri THE EFFECTS OF MESENCHYMAL STEM CELL THERAPY ON COLON ANASTOMOSIS IN RATS SUBJECTED TO RADIOTHERAPY https://orcid.org/0000-0002-2244-9875 Topuk Kübra Department of General Surgery, Bilecik State Hospital, Bilecik, Türkiye https://orcid.org/0000-0003-2817-1920 Şafak Adem Division of Transplantation, Department of General Surgery, Faculty of Medicine, Başkent University, ANKARA, TÜRKİYE https://orcid.org/0000-0003-3795-5794 Aydın Hüseyin Onur Independent Researcher, Department of General Surgery, ANKARA, TÜRKİYE https://orcid.org/0000-0002-5735-4315 Yıldırım Sedat Division of Transplantation, Department of General Surgery, Faculty of Medicine, Başkent University, ANKARA, TÜRKİYE https://orcid.org/0000-0001-6236-0050 Uysal Çağrı Ahmet Department of Plastic, Reconstructive and Aesthetic Surgery, Faculty of Medicine, Başkent University, ANKARA, TÜRKİYE https://orcid.org/0000-0001-8565-0667 Börcek Pelin Department of Pathology, Faculty of Medicine, Gazi University, ANKARA, TÜRKİYE https://orcid.org/0000-0001-9019-423X İncekaş Caner Department of Biostatistics, Faculty of Medicine, Başkent University, ANKARA, TÜRKİYE https://orcid.org/0000-0002-0294-6874 Yavuz Çolak Meriç Department of Biostatistics, Faculty of Medicine, Başkent University, ANKARA, TÜRKİYE https://orcid.org/0000-0001-9481-6307 Yavaş Güler Department of Radiation Oncology, Etlik City Hospital, University of Health Sciences, ANKARA, TÜRKİYE https://orcid.org/0000-0001-6543-4043 Özturan Özer Huriye Eda Department of Biochemistry, Faculty of Medicine, Başkent University, ANKARA, TÜRKİYE https://orcid.org/0000-0003-4805-1918 Türkoğlu Emine Suna Department of Biochemistry, Faculty of Medicine, Başkent University, ANKARA, TÜRKİYE 04 27 2026 28 1 77 83 10 15 2025 12 17 2025 Copyright © 1999, Kırıkkale Üniversitesi Tıp Fakültesi Dergisi 1999 Kırıkkale Üniversitesi Tıp Fakültesi Dergisi

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.

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.

 Colorectal neoplasms radiotherapy anastomotic leak mesenchymal stem cells wound healing. Kolorektal neoplaziler radyoterapi anastomoz kaçağı mezenkimal kök hücreler yara iyileşmesi. This study supported by Baskent University Research Fund. DA 22/01 Frattini M, Balestra D, Suardi S, et al. Different genetic features associated with colon and rectal carcinogenesis. Clin Cancer Res. 2004;10(12 Pt 1):4015-4021. Yang Q, Qu R, Lu S, Zhang Y, Zhang Z, Fu W. Biological and Clinical Characteristics of Proximal Colon Cancer: Far from Its Anatomical Subsite. Int J Med Sci. 2024;21(10):1824-1839. Pommergaard HC, Gessler B, Burcharth J, Angenete E, Haglind E, Rosenberg J. Preoperative risk factors for anastomotic leakage after resection for colorectal cancer: a systematic review and meta-analysis. Colorectal Dis. 2014;16(9):662-671. Wang H, Wei XZ, Fu CG, Zhao RH, Cao FA. Patterns of lymph node metastasis are different in colon and rectal carcinomas. World J Gastroenterol. 2010;16(42):5375-5379. Cammà C, Giunta M, Fiorica F, Pagliaro L, Craxì A, Cottone M. Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA. 2000;284(8):1008-1015. Kruschewski M, Rieger H, Pohlen U, Hotz HG, Buhr HJ. Risk factors for clinical anastomotic leakage and postoperative mortality in elective surgery for rectal cancer. Int J Colorectal Dis. 2007;22(8):919-927. Telem DA, Chin EH, Nguyen SQ, Divino CM. Risk factors for anastomotic leak following colorectal surgery: a case-control study. Arch Surg. 2010;145(4):371-376. Kapiteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001;345(9):638-646. Marijnen C a. M, Kapiteijn E, van de Velde CJH, et al. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial. J Clin Oncol. 2002;20(3):817-825. Tibbs MK. Wound healing following radiation therapy: a review. Radiother Oncol. 1997;42(2):99-106. Dormand EL, Banwell PE, Goodacre TEE. Radiotherapy and wound healing. Int Wound J. 2005;2(2):112-127. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211-228. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279-4295. Ceelen W, El Malt M, Cardon A, Berrevoet F, De Neve W, Pattyn P. Influence of preoperative high-dose radiotherapy on postoperative outcome and colonic anastomotic healing: experimental study in the rat. Dis Colon Rectum. 2001;44(5):717-721. Yoo JH, Shin JH, An MS, et al. Adipose-tissue-derived Stem Cells Enhance the Healing of Ischemic Colonic Anastomoses: An Experimental Study in Rats. J Korean Soc Coloproctol. 2012;28(3):132-139. Gursel MF, Malazgirt Z, Gursel B, Cakir S, Eren Z, Isildak I. Effects of preoperative conventional and hyperfractionated radiotherapy on the healing of rat colonic anastomoses. Onkologie. 2009;32(6):326-330. Yang Y, Wang Q, Luo J, et al. Superoxide Dismutase Mimic, MnTE-2-PyP Enhances Rectal Anastomotic Strength in Rats after Preoperative Chemoradiotherapy. Oxid Med Cell Longev. 2020;2020:3509859. Agren MS, Andersen TL, Mirastschijski U, et al. Action of matrix metalloproteinases at restricted sites in colon anastomosis repair: an immunohistochemical and biochemical study. Surgery. 2006;140(1):72-82. Waddell A, Ahrens R, Steinbrecher K, et al. Colonic eosinophilic inflammation in experimental colitis is mediated by Ly6C(high) CCR2(+) inflammatory monocyte/macrophage-derived CCL11. J Immunol. 2011;186(10):5993-6003.