Tunç AKKOÇ, Pınar Kahraman KOYTAK, Deniz GENÇ, Kayıhan ULUÇ, Tülin TANRIDAĞ, Noushin ZİBANDEH, Muazzez GÖKALP

Dental Folikül Mezenkimal Kök Hücreleri Amyotrofik Lateral Skleroz Hastalarının Lenfositlerinde CD4+Foxp3+ T-Regülatör Hücreleri Arttırdı

Amaç: Amyotrofik lateral skleroz (ALS) motor nöronların dejenerasyonuna sebep olan bir hastalıktır. Günümüzde ALS tedavisinde kullanılan tek ilaç riluzoldür; ancak bu ilacın faydası sınırlıdır. Kök hücre temelli tedaviler ALS için yeni bir tedavi seçeneğidir ve bu hastalık üzerin anti-inflamatuar etkisi olduğu gösterilmiştir. Bu çalışmada dental folikül mezenkimal kök hücrelerin (DFSCs) ALS hastalarından izole edilen periferal kan mononükleer hücreler (PBMC) üzerindeki immün baskılayıcı etkisi araştırılmıştır. Yöntemler: Sağlıklı bireylerin molar dişlerinden izole edilen DFSCs’ler PBMC izolasyonundan 48 saat önce 48 kuyulu hücre kültür plaklarına ekildi. ALS hastalarının ve sağlıklı bireylerin venöz kan örneklerinden PBMC izolasyonu yapıldı ve DFSCs’nin varlığında ve yokluğunda kültürü yapıldı. 72 saatlik kültür süresinin sonunda lenfosit proliferasyonu, apoptoz ve CD4+FoxP3+ regulator T hücre oranları analiz edildi. Bulgular: DFSCs ile birlikte kültürü yapılan ALS hastalarının lenfositlerinde CD4+FoxP3+ regulator T hücre oranlarının arttığı ve lenfosit proliferasyonunda azalma olduğu gösterilmiştir. Bunun yanı sıra DFSCs’ler ALS hastalarının lenfositlerinde apoptotik etkiyi arttırırken sağlıklı bireylerin lenfositlerinde hücre canlılığını koruduğu gözlemlenmiştir. Sonuç: Çalışmamızda DFSCs’in ALS hastalarının lenfositlerinde inflamatuar yanıt üzerinde baskılayıcı etkisi olduğu gösterilmiştir ve ALS dahil diğer nöroinflamatuar hastalıkların tedavisinde yeni bir seçenek olarak kullanılabilir.

Anahtar Kelimeler:

Amyotrofik lateral skleroz, dental folikül mezenkimal kök hücreler, immün baskılama

Dental Follicle Mesenchymal Stem Cells Enhance CD4+Foxp3+ Regulatory T Cells in the Lymphocytes of Amyotrophic Lateral Sclerosis Patients

Objective: Amyotrophic lateral sclerosis (ALS) is a disorder that causes the degeneration of motor neurons. Currently, riluzole is the only effective drug used to treat ALS; however, it has limited clinical benefits. Stem cell-based therapy has been studied as a potential novel treatment strategy for ALS and has shown to have an anti-inflammatory effects when treating this disease. In this study, we studied the immunosuppressive effect of dental follicle mesenchymal stem cells (DFSCs) on peripheral blood mononuclear cells (PBMCs) of ALS patients. Methods: DFSCs were isolated from the third molar teeth of healthy individuals, and cells were seeded in the 48 well plate 48 hours prior to PBMC isolation. PBMCs were isolated from venous blood samples of ALS patients and healthy volunteers and were cultured in the presence or absence of DFSCs. After 72 h of culture period lymphocyte proliferation, apoptosis and CD4+FoxP3+ regulatory T-cell ratios were analyzed. Results: Analysis revealed an increase in the number of CD4+FoxP3+ regulatory T cells and a decrease in the proliferative responses of lymphocytes with DFSCs. In addition, DFSCs enhanced the apoptotic effect of the lymphocytes of ALS patients, but increased cell survival in healthy individuals. Conclusion: Our study showed that DFSCs regulate inflammatory responses of lymphocytes in ALS patients and that they can be a novel therapeutic approach for treating neuroinflammatory diseases including ALS.

Keywords:

Amyotrophic lateral sclerosis, dental follicle mesenchymal stem cells, immunosuppression,

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