Mezenkimal Kök Hücreler ve İmmünomodülasyon Fonksiyonları

Yıl 2020, Cilt: 6 Sayı: 3, 324 - 333, 01.01.2020

Erhan Cebeci Türkan Yanık Emre Çetindağ Kerem Yanar Gizem Korkmaz Emin Türkay Korgun

Öz

Mezenkimal kök hücreler MKH kendilerini yenileme ve özellikle mezoderm kaynaklı hücreler olan osteoblastlar, adipositler ve kondrositlere olmak üzere, ektodermal ve endodermal kaynaklı hücrelere de farklılaşabilme yeteneği ile tanınmaktadırlar. Farklılaşma yeteneklerinden dolayı, MKH’ler doku mühendisliğinde terapötik uygulamalar için umut verici adaylar olarak ortaya çıkmaktadır. Ayrıca plasental MKH’ler; plasentanın doğumdan sonra atılan bir doku olması, hücre izolasyonunun kolay olması, etik tartışmalara yol açmaması ve kültür ortamında yüksek bölünme kapasitesi gibi özellikleri nedeniyle oldukça fazla tercih edilen kök hücrelerdir. İmmünosüpresif etkisi bulunan mezenkimal kök hücrelerin bağışıklık yanıtının düzenlenmesinde rol oynadığı ve bağışıklık yanıtı baskıladığı kanıtlanmıştır. Biz bu derlemede MKH’lerin başta T hücreler olmak üzere dendritik hücre DH ve diğer immün sistem hücreleri üzerine olan immünomodülatör etkilerini tartıştık. Bu bağlamda, MKH’ler dendritik hücrelerin olgunlaşmasını, sitokin üretimini ve T hücre uyarıcı kapasitesini etkin bir şekilde inhibe eder. Ayrıca, doğal öldürücü hücrelerin NK ve T lenfositlerin proliferasyonunu, sitokin sekresyonunu ve sitotoksik potansiyelini belirgin şekilde bozarlar. Çeşitli hayvan modelleri, MKH’lerin immün düzenleyici özelliklerini doğrular. Bu nedenle uygulanan MKH’ler, akut graft versus-host hastalığının GVHD tedavisinde kullanılabilmektedirler. Şiddetli akut GVHD hastalarıyla yapılan klinik çalışmalar, MKH’lerin uygulanmasının önemli klinik yanıtlarla sonuçlandığını ortaya koymaktadır. In-vitro miks-lenfosit çalışmalarında, kültüre mezenkimal kök hücrelerinin ilave edilmesi ile birlikte alloreaktif T hücre yanıtının baskılandığı saptanmıştır. Bu özelliği ile allojeneik hematopoietik kök hücre nakillerinde mezenkimal kök hücre infüzyonu sadece engrafmanı hızlandırmayıp, aynı zamanda akut ve kronik Graft-Versus-Host Hastalığı sıklığını da azaltmaktadır. İmmünomodülatör yetenekleri ve düşük immünojenisiteleri nedeniyle, MKH’ler, immün aracılı hastalıkların önlenmesi ve tedavisi için umut verici adaylardır

Anahtar Kelimeler

Mezenkimal Kök Hücre, Plasenta, İmmünomodülasyon

Mesenchymal Stem Cells and Immunomodulatory Functions

Öz

Mesenchymal stem cells MSC are known for their regeneration ability and differentiation into various cell types, especially mesodermal cells such as osteoblasts, adipocytes and chondrocytes, but also ectodermal and endodermal cell types. Due to their differentiation abilities, MDGs are emerging as promising candidates for therapeutic applications in tissue engineering. Placental MSCs are highly preferred because the placenta is easy to obtain as it is discarded after birth, it is easy to isolate the MSCs, the process does not lead to ethical discussions, and the dividing capacity in culture medium is high. Mesenchymal stem cells with an immunosuppressive effect have been proven to play a role in regulating the immune response by suppressing it. Here, we reviewed the immunomodulatory effects of MSCs on dendritic cells DH , and other immune system cells, especially T cells. In this context, MSCs effectively inhibit the maturation of dendritic cells, cytokine production, and the stimulus capacity of T cells. In addition, MSCs significantly impair the proliferation, cytokine secretion and cytotoxic potential of natural killer cells NK and T lymphocytes. Various animal models have confirmed the immunoregulatory properties of MSCs. Therefore, MSC treatment can be used for acute graft versus host disease GVHD . Clinical studies on severe acute GVHD patients suggest that the application of MSCs results in significant clinical responses. In-vitro mix-lymphocyte studies revealed that the alloreactive T cell response was suppressed by the addition of mesenchymal stem cells to the culture. With this feature, mesenchymal stem cell infusion in allogeneic hematopoietic stem cell transplantation not only accelerates the engraftment but also reduces the frequency of acute and chronic Graft-Versus-Host Disease. Because of their immunomodulatory abilities and low immunogenicity, MSCs are promising candidates for the prevention and treatment of immune-mediated diseases.

Anahtar Kelimeler

Mesenchymal stem cells, Placenta, Immunomodulation

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