ONUR UYSAL, Tuğba SEVİMLİ, Sibel GÜNEŞ, Ahmad TOKHİ, Ceren ÖZEL, Ayla SARIBOYACI

İnsan Amniyon Sıvısı Kökenli Mezenkimal Kök Hücrelerin İmmunosupresyon Etkileri: Treg Regülasyonu

Amaç: Mezenkimal kök hücreler (MKH), rejeneratif, immunosupresif, non-immunojenik, anjiyojenik, antiapoptotik ve antiinflamatuvar özellikleri sayesinde hem preklinik araştırmalarda hem de kilinikte önem taşımaktadır. MKH’lerin immunosupresif fonksiyonlarının keşfi, otoimmün hastalıklarda patojenik immun yanıtı düşürmek için yeni terapötik araç olarak araştırmalara konu olmuştur. Plasenta, göbek kordonu ve amniyon sıvısı; kemik iliği ve yağ kökenli MKH’lere göre non-invazif eldesi ve pluripotensi kapasitesiyle avantajlı kök hücre kaynakları arasındadır. Bu çalışmada immün yanıtların incelenmesi için in vitro bir model kullanılarak insan amniyotik sıvı kökenli MKH’lerin (iAS-MKH), fitohemaglütinin ile aktive edilmiş T-hücreleri (PHA-T hücreleri) üzerindeki etkisini; hücre proliferasyonu, apoptoz, sitokin düzeyleri ve regülatuar T hücre (Treg) farklılaşması açısından analiz edilmesi amaçlandı.Gereç ve yöntem: Periferik kandan immunoseleksiyon yöntemi ile izole edilen T-hücreleri karakterize edilip PHA ile uyarıldıktan sonra, iAS-MKH’ler ile insertler kullanılarak indirekt yolla 4 gün ko-kültür (transwell) edildi. Kültür sonrasında PHA-T-hücreleri flow sitometri ve ELISA ile hücre canlılığı ve proliferasyon, sitokin düzeyleri, Treg-farklılaşması ve apoptotik açıdan analiz edildi.Bulgular: iAS-MKH'lerin; in vitroda ko-kültür edildikleri PHA-T hücrelerinin sitokin profilini değiştirerek, canlılık ve proliferasyonu azaltarak ve apoptoz ve Treg farklılaşmasını indükleyerek immunosupresif etki gösterdiği gözlendi. Sonuç: Erken dönemde (prenatal-natal) ve non-invazif tekniklerle eldesi ve atık bir doku olması şeklinde avantajları olan amniyon sıvısındaki bu kök hücrelerin, immunosupresif etkileri olduğu ve ileriye yönelik olarak daha ayrıntılı analizlerle ve in vivo çalışmalarla desteklenmesi gerektiği sonucuna varıldı.

Anahtar Kelimeler:

insan amniyon sıvısı, mezenkimal kök hücre, immunosupresyon

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