Tissue engineering in the treatment of congenital diaphragmatic hernia

KUMBASAR, Ulaş; UYSAL, SERKAN; DİKMEN, Erkan

Tissue engineering in the treatment of congenital diaphragmatic hernia

Ulaş KUMBASAR, (Department of Thoracic Surgery, Hacettepe University, Faculty of Medicine, Ankara,)

Erkan DİKMEN, (Department of Thoracic Surgery, Hacettepe University, Faculty of Medicine, Ankara,)

Serkan UYSAL (Department of Thoracic Surgery, Bülent Ecevit University, Faculty of Medicine, Zonguldak, TURKEY)

Turkish Journal of Clinics and Laboratory

1 0

Yıl: 2017 Cilt: 8 Sayı: 3 Sayfa Aralığı: 124 - 129 Metin Dili: Türkçe İndeks Tarihi: 29-07-2022

Tissue engineering in the treatment of congenital diaphragmatic hernia

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 Kelime:

Konular: Tıbbi Araştırmalar Deneysel Tıbbi Laboratuar Teknolojisi

Konjenital diyafragma herni tedavisinde doku mühendisliği

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 Kelime:

Konular: Tıbbi Araştırmalar Deneysel Tıbbi Laboratuar Teknolojisi

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

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APA	KUMBASAR U, DİKMEN E, UYSAL S (2017). Tissue engineering in the treatment of congenital diaphragmatic hernia. , 124 - 129.
Chicago	KUMBASAR Ulaş,DİKMEN Erkan,UYSAL SERKAN Tissue engineering in the treatment of congenital diaphragmatic hernia. (2017): 124 - 129.
MLA	KUMBASAR Ulaş,DİKMEN Erkan,UYSAL SERKAN Tissue engineering in the treatment of congenital diaphragmatic hernia. , 2017, ss.124 - 129.
AMA	KUMBASAR U,DİKMEN E,UYSAL S Tissue engineering in the treatment of congenital diaphragmatic hernia. . 2017; 124 - 129.
Vancouver	KUMBASAR U,DİKMEN E,UYSAL S Tissue engineering in the treatment of congenital diaphragmatic hernia. . 2017; 124 - 129.
IEEE	KUMBASAR U,DİKMEN E,UYSAL S "Tissue engineering in the treatment of congenital diaphragmatic hernia." , ss.124 - 129, 2017.
ISNAD	KUMBASAR, Ulaş vd. "Tissue engineering in the treatment of congenital diaphragmatic hernia". (2017), 124-129.

APA	KUMBASAR U, DİKMEN E, UYSAL S (2017). Tissue engineering in the treatment of congenital diaphragmatic hernia. Turkish Journal of Clinics and Laboratory, 8(3), 124 - 129.
Chicago	KUMBASAR Ulaş,DİKMEN Erkan,UYSAL SERKAN Tissue engineering in the treatment of congenital diaphragmatic hernia. Turkish Journal of Clinics and Laboratory 8, no.3 (2017): 124 - 129.
MLA	KUMBASAR Ulaş,DİKMEN Erkan,UYSAL SERKAN Tissue engineering in the treatment of congenital diaphragmatic hernia. Turkish Journal of Clinics and Laboratory, vol.8, no.3, 2017, ss.124 - 129.
AMA	KUMBASAR U,DİKMEN E,UYSAL S Tissue engineering in the treatment of congenital diaphragmatic hernia. Turkish Journal of Clinics and Laboratory. 2017; 8(3): 124 - 129.
Vancouver	KUMBASAR U,DİKMEN E,UYSAL S Tissue engineering in the treatment of congenital diaphragmatic hernia. Turkish Journal of Clinics and Laboratory. 2017; 8(3): 124 - 129.
IEEE	KUMBASAR U,DİKMEN E,UYSAL S "Tissue engineering in the treatment of congenital diaphragmatic hernia." Turkish Journal of Clinics and Laboratory, 8, ss.124 - 129, 2017.
ISNAD	KUMBASAR, Ulaş vd. "Tissue engineering in the treatment of congenital diaphragmatic hernia". Turkish Journal of Clinics and Laboratory 8/3 (2017), 124-129.