Pediatrik Kanser Hastalarında Fertilitenin Korunması
Özet
Pediatrik kanser hastalarında uygulanan kemoterapi ve radyoterapi tedavileri germ hücrelerine ciddi düzeyde zarar vererek bu hastaların yaklaşık %48'inde infertiliteye yol açmaktadır. Erişkin kanser hastalarında tedavi öncesinde sperm kriyoprezervasyonu standart ve etkili bir metot olarak uygulanırken, henüz puberteye girmemiş çocuklarda sperm üretimi başlamadığı için fertilitenin korunmasında spermatogonyal kök hücre (SKH) temelli tedavi yaklaşımları öne çıkmaktadır. Kanser tedavisi başlatılmadan önce hastalardan alınan testis biyopsileri testiküler hücre süspansiyonu (THS) veya testiküler doku (TD) şeklinde dondurularak muhafaza edilebilmektedir. Kriyoprezervasyon süreçlerinde kontrollü yavaş dondurma (CSF), kontrollü olmayan yavaş dondurma (USF) ve vitrifikasyon teknikleri ile DMSO, EG, PrOH, GLY ve sükroz gibi çeşitli kriyoprotektan ajanlar tercih edilmektedir. Testis niş ortamında yer alan Sertoli, Leydig, peritübüler miyoid, makrofaj ve endotel hücreleri; GDNF, bFGF, CSF1 gibi büyüme faktörleri ve hormonlar salgılayarak SKH'lerin kendini yenileme, çoğalma ve farklılaşma süreçlerini düzenlemektedir. Maymun ve insan testis biyopsileriyle yürütülen deneysel çalışmalar, çözme işleminin ardından SKH'lerin canlılıklarını ve fonksiyonel niteliklerini koruduğunu, hatta primatlarda otogreftleme yöntemiyle fonksiyonel sperm ve canlı yavru doğumunun sağlandığını kanıtlamıştır. Ancak pediatrik biyopsi örneklerinin küçüklüğü nedeniyle SKH sayısının yetersiz olması, in vitro kültür aşamasında ksenojenik kontaminasyon riski ve olası kanser hücrelerinin hastaya yeniden transplante edilme tehlikesi, klinik uygulamalara geçilmeden önce bertaraf edilmesi gereken başlıca engellerdir.1
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