Mezenkimal Kök Hücre Üretiminde İn Vitro Temelli Metabolomik ve Analizler

Karaağaç Akyol, T. Metabolomic And Analyzes In In-Vitro Based On The Production Of Mesenchimal Stem Cells, Hacettepe University Graduate School of Health Sciences Stem Cells Program Doctor of Philosophy Thesis, Ankara, 2020. In our study, the effects of different additions MSC’s exposed to FBS, PL, PPP and BMP and also inflammatory environment in the presence of LPS were investigated. These serum additions’s effects on MSC proliferation, differentiation characteristics and metabolomic profile of cells and culture medium were studied. As a result of analysis, 479 metabolites changed significantly and 242 metabolites were identified intracellularly. 605 extracellular metabolites were detected in culture supplements, culture media and cell culture supernatants and 116 of them have been identified. MSCs in PL-containing media are mostly directed to glycolytic metabolism, glutamine consumption is high and cells are directed to glutaminolysis and this is thought that these pathways may have a role in the case of inflammation and MSCs may have more immunosuppressive, antiinflammatory and senescence inhibitory properties in PL. In general FBS-containing medium’s amino acid levels were higher than other additions and it has been determined that methionine, threonine and alanine are consumed more in FBS medium, glutamic acid and aspartic acid are consumed more in the PL medium. LysoPC, which has been shown to be important in determining the immunological properties of cells was higher in PL, LysoPE was higher in FBS and it was thought that the immunomodulatory properties of the cells grown with these additives may be different. Findings obtained as a result of LPS stimulation supported this, too.Karaağaç Akyol, T., Mezenkimal Kök Hücre Üretiminde In Vitro Temelli Metabolomik Ve Analizler, Hacettepe Üniversitesi Sağlık Bilimleri Enstitüsü Kök Hücre Programı Doktora Tezi, Ankara, 2020. Çalışmamızda MKH’ler FBS, PL, PPP ve KİP varlığında ve ayrıca LPS varlığında inflamatuvar ortama maruz bırakılarak farklı eklentilerin etkisi araştırılmıştır. Eklentilerinin MKH proliferasyonu, farklılaşma özelliklerine etkileri, hücrelerin ve kültür ortamının metabolomik profili çalışılmıştır. Analizler sonucunda 479 metabolit anlamlı değişmiş, intrasellüler 242 metabolit tanımlanmıştır. Besiyerleri ve hücre kültürleri süpernatanlarında 605 ekstrasellüler metabolit saptanmış, bunların 116’sı tanımlanmıştır. PL içeren ortamda MKH’lerin daha çok glikolitik metabolizmaya yöneldiği, glutamin tüketiminin yüksek olup hücrelerin glutaminolizise yöneldiği ve inflamasyon durumunda bu yolakların rolü olabileceği, MKH’lerin PL ortamında daha immünsupresif, antiinflamatuvar ve senesensi önleyici özelliğe sahip olabileceği düşünülmüştür. FBS içeren besiyeri ortamında genel olarak amino asit seviyeleri diğer eklentilere göre daha yüksek bulunmuş, metionin, treonin ve alaninin FBS ortamında, glutamik asit ve aspartik asitin ise PL ortamında daha fazla tüketildiği saptanmıştır. Hücrelerin immünolojik özelliklerini belirlemede önemi gösterilmiş olan LysoPC PL’ta, LysoPE FBS’de daha yüksek bulunmuş, bu eklentilerle çoğaltılan hücrelerin immünmodulatuvar özelliklerinin farklı olabileceği düşünülmüştür. LPS uyarımı sonucu elde edilen bulgular da bunu desteklemiştir

A nation-wide survey of patients with homozygous familial hypercholesterolemia phenotype undergoing LDL-apheresis in Turkey (A-HIT 1 registry)

Background and aims: Homozygous familial hypercholesterolemia (HoFH) is a genetic condition characterized by lethally high levels of low-density lipoprotein cholesterol (LDL-C) from birth, and requires rapid and aggressive intervention to prevent death due to coronary heart disease and/or atherosclerosis. Where available, lipoprotein apheresis (LA) is the mainstay of treatment to promote survival

Mental status and physical activity in patients with homozygous familial hypercholesterolemia: A subgroup analysis of a nationwide survey (A-HIT1 registry)

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening disease due to high serum low-density lipoprotein (LDL) cholesterol levels. LDL cholesterol-lowering interventions are fundamental for patients with HoFH

What have we learned from Turkish familial hypercholesterolemia registries (A-HIT1 and A-HIT2)?

Background and aims: Familial hypercholesterolemia (FH) is a common genetic disease of high-level cholesterol leading to premature atherosclerosis. One of the key aspects to overcome FH burden is the generation of largescale reliable data in terms of registries. This manuscript underlines the important results of nation-wide Turkish FH registries (A-HIT1 and A-HIT2)