Konjenital diyafragma hernisi tedavisinde doku mühendisliği

Yıl 2017, Cilt: 8 Sayı: 3, 124 - 129, 01.06.2017

Ulaş Kumbasar , Erkan Dikmen Serkan Uysal

https://doi.org/10.18663/tjcl.289871

Öz

Doğumsal diyafragmatik herni (CDH), en sık
karşılaşılan konjenital anomalilerden biri olup abdominal organların göğsüne herniyasyonuna
neden olan diyafram kusurunun varlığı olarak tanımlanmaktadır. Son yıllarda
ileri tedavi stratejileri getirilmesine rağmen hayatta kalma oran, % 70
civarında kalmışve geliştirilememiştir. KKH'de kötü sonuçların başlıca
belirleyicileri pulmoner hipoplazi ve pulmoner hipertansiyondur. Akciğer
fonksiyonlarını ve sağkalımı geliştirmek için çeşitli cerrahi müdahaleler ve
yeni tıbbi tedaviler denmektedir, ancak istenilen seviyeden daha az orandadır.
Protez materyali ile diyafragma defektinin onarımının, takip sırasında yüksek
komplikasyonlar ve rekürrens oranları ile ilişkili olduğu tespit edilmiştir. Bu
nedenle, rejeneratif ilaç hem hipoplazi akciğerlerde hücresel fonksiyonu
indükleyerek (kök hücre tedavisi) hem de işlevsel bir miyojenik yama (doku
mühendisliği) geliştirerek, CDH'de alternatif bir tedavi stratejisi olarak
düşünülmektedir.Solunum yetmezliğine sebep olan ciddi pulmoner hipoplazi ve
hipertansiyon ile doğan CDH'li yenidoğanların yaklaşık % 30'unun hayatta
kalması pulmoner hipoplazi derecesi ile ilişkili olduğundan, bu dereceyi
prenatal olarak değerlendirmek büyük önem taşır. Prenatal ultrasonografi (US)
ve manyetik rezonans görüntüleme (MRI) iki ana tanı aracıdır. CDH'de pulmoner
hipoplazi ve hipertansiyonu iyileştirmek için çeşitli doğum öncesi tedavi
stratejileri denendi. Vitamin A, kortikosteroidler, C vitamini, E,
N-asetilsistein, fosfodiesteraz inhibitörleri, glukagon benzeri peptit 1
agonistleri ve tirozin kinaz inhibitörleri gibi antioksidanlar hayvan
çalışmalarında analiz edildi ve değişken sonuçlar gösterdi. İnsanlar üzerinde
çok az çalışma olduğu için, bu terapilerin klinik yararlarını teyit edebilmek
için ileri aşama araştırmalar insanlar üzerinde olmalıdır. Doğumdan sonra
bebeğe destekleyici tedavisinin yanı sıra solunum yetmezliği durumunda tercihen
yüksek frekanslı salınımlı ventilasyon ile solunum desteği de uygulanmalıdır.
Eksojen kök hücreler, özellikle AFS hücreleri akciğer gelişimini hem çeşitli
pulmoner hücre tiplerine entegre ederek, hem de anti-inflamatuvar ve
immünomodülatör etkiler yoluyla parakrin modele göre veya doğal progenitör
hücreleri aktive ederek geliştirebilir. Ancak, akciğer hasarının altında yatan
mekanizmayı ve kök hücrelerin moleküler tepkisini anlamak için, özellikle de
insanlarda yapılacak daha ileri araştırmalara ihtiyaç vardır. Doğum öncesi
tarama yöntemlerindeki ilerlemeler sayesinde, artık gebelikteki en büyük
genetik bozuklukların çoğunu tespit etme ve postnatal dönemde optimal tedavi
stratejisi sunma olanaği bulunmaktadır. CDH'li çocukların tedavisinde
rejeneratif tıbbın uygulanmasına ilişkin hayvan çalışmalarının sonuçları
gelecek vadetmektedir. Yakın gelecekte özellikle güvenlik ve etik konular
çerçevesinde yoğunlaşan daha ileri çalışmaların 
desteğiyle, klinik olarak uygulanması için gerekli kanıtlar bu
çalışmalar ile sağlanacaktır.

Anahtar Kelimeler

doğumsal, diyafragma hernisi, doku mühendisliği

Tissue engineering in the treatment of congenital diaphragmatic hernia

Öz

Congenital
diaphragmatic hernia (CDH) is one of the most common major congenital anomalies
and is described as the presence of a diaphragmatic defect that leads the
herniation of abdominal organs into the chest. Although advanced treatment strategies are introduced over the recent years, they have not really
improved the survival rate which stayed at around 70%. Major determinants of
poor outcome in CHD are pulmonary hypoplasia and pulmonary hypertension.
Various surgical interventions and novel medical therapies
are attempted to improve lung function and survival but remains less than
desired. Repair of the diaphragmatic defect with prosthetic materials was found
to be associated with high rates of complications and recurrences during
follow-up. Therefore, regenerative medicine should be
considered as an alternative treatment strategy in CDH both by inducing
cellular function in the hypoplastic lungs (stem cell therapy) and by
developing a functional myogenic patch (tissue engineering). Nearly 30% of
infants who have CDH born with severe pulmonary
hypoplasia and hypertension which may lead to respiratory failure and prompt
mechanical support, since the survival of these newborns relate to the degree
of pulmonary hypoplasia, accurate prenatal evaluation of this degree is of paramount importance. The two main
diagnostic tools which could be used for this purpose are prenatal ultrasound
(US) and magnetic resonance imaging (MRI). Various prenatal treatment
strategies have been tried to cure pulmonary hypoplasia and hypertension in CDH. Vitamin A,
corticosteroids, antioxidants such as vitamin C, E,
N-acetylcystein, phosphodiesterase inhibitors, glucagon-like peptide 1 agonists
and tyrosine kinase inhibitors have all been analyzed in animal studies and
demonstrated variable results. Since there are very
few human studies, further researches should be performed in humans confirming
the clinical benefit of these therapies. Due to the advancements in prenatal
screening methods, we, now have the ability to detect most of the major genetic disorders in gestation and have chance to
provide optimal treatment strategy in the postnatal period. Results of the
animal studies regarding the application of regenerative medicine for treatment
of children with CDH are encouraging. Hopefully, with
the support of further studies focusing especially on safety and ethical
issues, the near future will provide us the evidence necessary for their
application in our clinical practice.  

Anahtar Kelimeler

congenital, diaphragmatic hernia, tissue engineering

Kaynakça

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