Kardiyak Kök Hücreler

Yıl 2017, Cilt: 6 Sayı: 2, 505 - 508, 01.06.2017

Emrah İpek Recai Tunca

Öz

Özbilgi/Amaç: Yapı ve işlev bakımından birbirinden oldukça farklı olan kök hücreler, embriyo kök hücresi ve yetişkin kök hücreler olmak üzere iki ana başlık altında sınıflandırılır. Embriyo kök hücresi, embriyo gövdesine ait bütün hücre tabakalarını ve bu tabakalardan köken alan doku ve organları oluşturma yeteneğindedir. Dokuya özgü kök hücreler olarak da adlandırılan yetişkin kök hücreler ise, embriyo kök hücrelerine kıyasla daha sınırlı sayıda hücre türüne farklılaşabilir. Kemik iliği, deri, karaciğer, bağırsak gibi kendi kendini yenileme yeteneği yüksek olan organlarda dokuya özgü kök hücrelerin varlığı uzun süredir bilinmektedir. Kalpte bulunan kök hücrelere dair bilgiler ise oldukça yenidir. Geçmişte yenilenme yetkinliği olmadığı düşünülen kalp, günümüzde belli oranda yenilendiği kabul edilen bir organ olarak nitelenmektedir. Bu derlemenin amacı, kalpte şimdiye kadar tanımlanan kök hücreler, bu hücrelerin kalbi oluşturan hücrelere farklılaşma yetkinliği ve birtakım hastalık modellerinde tedavi edici etkinlikleri hakkında bilgi vermektir. Sonuç: Kalbin kendi kendini yenileme yeteneği konusunda görüş ayrılıkları olsa da, kalbin gerektiğinde belli oranda yenilenme yetkinliği olan bir organ olduğu birçok araştırmacı tarafından ortaya konmuştur. Kalpteki kök hücreler, hücre yüzey reseptörlerine göre c-kit+ kök hücreler, Sca-1+ kök hücreler ve yan küme hücreleri olarak sınıflandırılır. Bu yüzey reseptörüne sahip hücrelerin; kardiyak miyosit, endotel hücresi ve düz kas hücresine farklılaşma yeteneğinde olduğu in vitro ve in vivo çalışmalarla gösterilmiştir. Kardiyak kök hücreler kalp dokusunda niş adı verilen mikroçevrede bulunurlar. Kök hücreler burada çoğalabilir, kararlanabilir, farklılaşabilir ve gerektiğinde bu bölgeyi terk ederek onarım süreçlerine katılabilirler. Bu hücrelerin kalbi oluşturan hücrelere farklılaşma yetkinliğinin birçok araştırmacı tarafından ortaya konması günümüzde medikal yöntemlerle tedavi edilemeyen kalp hastalıklarının tedavisi için ümit kaynağı olmuştur. Bu alandaki deneysel ve klinik çalışmalar artarak devam etmektedir.

Anahtar Kelimeler

Kardiyak kök hücre, kardiyak niş, c-kit, Sca-1

Cardiac Stem Cells

Öz

Backround/Aim: Stem cells are often classified into one of two categories: embryonic stem ES cells and non-embryonic ‘somatic’ or ‘adult’ stem cells. ES cells derived from the inner cell mass of a blastocyst are capable of differentiating into all cells of the three germ layers and the tissues and organs that originate from these layers. Adult stem AS cells can generate only a limited set of specialized cells characteristic of a particular tissue located throughout the body. It is known that AS cells have been found in organs with high self-renewal ability, such as bone marrow, skin, liver, and intestine. However, the information about the stem cells in the heart is quite new. The heart, which is thought to have not been renewed in the past, is now regarded as an organ that is considered to be somewhat renewed. The aim of this review is to give information about the stem cells which are defined up to now in the heart, the ability of these cells to differentiate into the cardiac cells and their potential therapeutic activity in various disease models. Conclusion: Cardiac stem cells are classified into three cell types based on the cell surface markers expression: c-kit+ stem cells, Sca-1+ stem cells and side population cells. Scientists now have evidence that cells with these receptors have differentiate cardiac cells such as cardiomyocytes, endothelial cells and smooth muscle cells. Cardiac stem cells are found in the microenvironment called the niche in the heart. When needed cardiac stem cells participate the process of tissue healing including: proliferation, differentiation and migration. The ability of these cells to differentiate into the heart forming cells has been demonstrated by many researchers and has been new hope for the treatment of heart diseases.

Anahtar Kelimeler

Cardiac stem cells, cardiac niche, c-kit, Sca-1

Kaynakça

• Anversa P, Leri A, Kajstura J (2006). Cardiac regeneration. J Am Coll Cardiol. 47(9):1769-76.
• Anversa P, Kajstura J, Rota M, Leri A (2013). Regenerating new heart with stem cells. J Clin Invest. 123(1):62-70.
• Bearzi C, Rota M, Hosoda T, Tillmanns J, Nascimbene A, De Angelis A, Yasuzawa-Amano S, Trofimova I, Siggins RW, Lecapitaine N, Cascapera S, Beltrami AP, D’Alessandro DA, Zias E, Quaini F, Urbanek K, Michler RE, Bolli R, Kajstura J, Leri A, Anversa P (2007). Human cardiac stem cells. Proc Natl Acad Sci USA. 104(35):14068-73.
• Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, Nadal- Ginard B, Silvestri F, Leri A, Beltrami CA, Anversa P (2001). Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med. 344(23):1750-7.
• Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, Kasahara H, Rota M, Musso E, Urbanek K, Leri A, Kajstura J, Nadal- Ginard B, Anversa P (2003). Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 114(6):763-76.
• Bergmann O, Bhardwaj RD, Bernard S, Zdunek S, Barnabé-Heider F, Walsh S, Zupicich J, Alkass K, Buchholz BA, Druid H, Jovinge S, Frisén J (2009). Evidence for cardiomyocyte renewal in humans. Science. 324(5923):98-102.
• Bersell K, Arab S, Haring B, Kühn B (2002). Neuregulin1/ErbB4 signaling induces cardiomyocyte proliferation and repair of heart injury. Cell. 138(2):257-70.
• Bu L, Jiang X, Martin-Puig S, Caron L, Zhu S, Shao Y, Roberts DJ, Huang PL, Domian IJ, Chien KR (2009). Human ISL1 heart progenitors generate diverse multipotent cardiovascular cell lineages. Nature. 460(7251):113-7.
• Can A. Kök Hücre Biyolojisi, Türleri ve Tedavide Kullanımları
• Can A (2009). Kök Hücre Tanımları. Kök Hücre Biyolojisi ve Klinik Uygulamalar. TÜBA Kök Hücre Çalışma Grubu Ankara, Türkiye Bilimler Akademisi. 20 pp:15-22
• Chen X, Wilson RM, Kubo H, Berretta RM, Harris DM, Zhang X, Jaleel N, MacDonnell SM, Bearzi C, Tillmanns J, Trofimova I, Hosoda T, Mosna F, Cribbs L, Leri A, Kajstura J, Anversa P, Houser SR (2007). Adolescent feline heart contains a population of small, proliferative ventricular myocytes with immature physiological properties. Circ Res. 100(4):536-44.
• Cliffe LJ, Humphreys NE, Lane TE, Potten CS, Booth C, Grencis RK (2005). Accelerated intestinal epithelial cell turnover: a new mechanism of parasite expulsion. Science. 308(5727):1463-5.
• Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, Jiang H, Wang Y, Keating MT (2005). p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev. 19(10):1175-87.
• Fuchs E, Tumbar T, Guasch G (2004). Socializing with the neighbors: stem cells and their niche. Cell. 116(6):769-78.
• Goldberg GS, Valiunas V, Brink PR (2004). Selective permeability of gap junction channels. Biochim Biophys Acta. 1662(1-2):96-101.
• Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P (1998). Myocyte proliferation in end-stage cardiac failure in humans. Proc Natl Acad Sci USA. 95(15):8801-5.
• Kajstura J, Urbanek K, Perl S, Hosoda T, Zheng H, Ogórek B, Ferreira- Martins J, Goichberg P, Rondon-Clavo C, Sanada F, D’Amario D, Rota M, Del Monte F, Orlic D, Tisdale J, Leri A, Anversa P (2010). Cardiomyogenesis in the adult human heart. Circ Res. 107(2):305- 15.
• Kasahara H, Bartunkova S, Schinke M, Tanaka M, Izumo S (1998). Cardiac and extracardiac expression of Csx/Nkx2.5 homeodomain protein. Circ Res. 82(9):936-46.
• Kondo M1, Wagers AJ, Manz MG, Prohaska SS, Scherer DC, Beilhack GF, Shizuru JA, Weissman IL (2003). Biology of hematopoietic stem cells and progenitors: implications for clinical application. Annu Rev Immunol. 21:759-806.
• Kubin T, Pöling J, Kostin S, Gajawada P, Hein S, Rees W, Wietelmann A, Tanaka M, Lörchner H, Schimanski S, Szibor M, Warnecke H, Braun T (2011). Oncostatin M is a major mediator of cardiomyocyte dedifferentiation and remodeling. Cell Stem Cell. 9(5):420-32.
• Laflamme MA, Murry CE (2011). Heart regeneration. Nature. 473(7347):326-35.
• Linke A, Müller P, Nurzynska D, Casarsa C, Torella D, Nascimbene A, Castaldo C, Cascapera S, Böhm M, Quaini F, Urbanek K, Leri A, Hintze TH, Kajstura J, Anversa P (2005). Stem cells in the dog heart are self-renewing, clonogenic, and multipotent and regenerate infarcted myocardium, improving cardiac function. Proc Natl Acad Sci USA. 102(25):8966-71.
• Matsuura K, Honda A, Nagai T, Fukushima N, Iwanaga K, Tokunaga M, Shimizu T, Okano T, Kasanuki H, Hagiwara N, Komuro I (2009). Transplantation of cardiac progenitor cells ameliorates cardiac dysfunction after myocardial infarction in mice. J Clin Invest. 119(8):2204-17.
• Molkentin JD, Lin Q, Duncan SA, Olson EN (1997). Requirement of the transcription factor GATA4 for heart tube formation and ventral morphogenesis. Genes Dev. 11(8):1061-72.
• Morrison SJ, Wandycz AM, Akashi K, Globerson A, Weissman IL (1996). The aging of hematopoietic stem cells. Nat Med. 2(9):1011-6.
• Perez-Moreno M, Jamora C, Fuchs E (2003). Sticky business: orchestrating cellular signals at adherens junctions. Cell. 112(4):535-48.
• Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, Kajstura J, Leri A, Anversa P (2002). Chimerism of the transplanted heart. N Engl J Med. 346(1):5-15.
• Sellers SE, Tisdale JF, Agricola BA, Metzger ME, Donahue RE, Dunbar CE, Sorrentino BP (2001). The effect of multidrug-resistance 1 gene versus neo transduction on ex vivo and in vivo expansion of rhesus macaque hematopoietic repopulating cells. 97(6):1888-91.
• Smith AG (2001). Embryo-derived stem cells: of mice and men. Annu Rev Cell Dev Biol. 17:435-62.
• Smith RR, Barile L, Cho HC, Leppo MK, Hare JM, Messina E, Giacomello A, Abraham MR, Marbán E (2007). Regenerative potential of cardiosphere-derived cells expanded from percutaneous endomyocardial biopsy specimens. Circulation. 115(7):896-908.
• Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, Leri A, Kajstura J, Quaini E, Anversa P (2003). Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA. 100(18):10440-5.
• Urbanek K, Torella D, Sheikh F, De Angelis A, Nurzynska D, Silvestri F, Beltrami CA, Bussani R, Beltrami AP, Quaini F, Bolli R, Leri A, Kajstura J, Anversa P (2005). Myocardial regeneration by activation of multipotent cardiac stem cells in ischemic heart failure. Proc Natl Acad Sci USA. 102(24):8692-7.
• Urbanek K, Cesselli D, Rota M, Nascimbene A, De Angelis A, Hosoda T, Bearzi C, Boni A, Bolli R, Kajstura J, Anversa P, Leri A (2006). Stem cell niches in the adult mouse heart. Proc Natl Acad Sci USA. 103(24):9226-31.
• Watt FM, Lo Celso C, Silva-Vargas V (2006). Epidermal stem cells: an update. Curr Opin Genet Dev. 16(5):518-24.
• Weissman IL, Anderson DJ, Gage F (2001). Stem and progenitor cells: origins, phenotypes, lineage commitments, and transdifferentiations. Annu Rev Cell Dev Biol. 17:387-403.