Kök hücrede gen transferi ile istenen bir genin aktivasyonu veya susturulması uygulamalarının rejeneratif tıpta kullanımı
Öz
Özet
İnsan kök hücresi kendine benzeyen hücreler oluşturabilen ve farklılaşma potansiyeline sahip özellikte hücrelerdir. Embriyonik kök hücreler farlı hücre tiplerine dönüşebildiği için kök hücre biyolojisinde ve rejeneratif tıpta paha biçilmez bir araçtır. Yeni gelişen gen teknolojileri ile ökaryot hücreye gen aktarımı mümkündür. Bu teknolojiler ile hücrede istenilen genlerin aktiflenmesi veya susturulması olasıdır. Uygun ortam sağlandığında normalde kapalı olan bazı genlerin aktif formlarının hücre çekirdeğine aktarılması ile farklanmış bir insan hücresinden indüklenmiş pluripotent kök hücreler elde edilmektedir. Bilindiği gibi, “small interference RNA” ve “micro RNA” lar hücrede gen fonksiyonlarını düzenlerler. Bu moleküller ökaryot hücrede gen susturulması amacı ile genellikle viral ve viral olmayan metodlar ile aktarılarak kullanılırlar. Gen susturulması teknolojisi, embriyonik kök hücre veya indüklenmiş pluripotent kök hücrelerin istenilen yönde örneğin bir nöron, pankreas veya kalp hücresi yönünde farklanmasında önemli bir araçtır. Tüm bu gelişmeler bize doku mühendisliği alanında hasta bazlı rejeneratif tıp uygulamalarının yapılabileceğini, kişiye özgü doku ve organ temininin mümkün olabileceğini göstermektedir.
Anahtar sözcükler: Embriyonal kök hücre, indüklenmiş pluripotent kök hücre, si RNA, mi RNA, rejeneratif tıp, gen transferi
Abstract
Human stem cell is a kind of special cell type which has self renewal capasity and differentiation potential. Embriyonic stem cells are an invaluable tool for stem cell biology and regenerative medicine as they have the capacity to differentiate into various functional cells. With the new gene technologies improved in recent years, it is possible to transfer a gene into a eukaryote cell. A desired gene can be activated or silenced via these technologies. In an appropriate condition, a differentiated human cell can be transformed into induced pluripotent stem cell by transforming the active form of some genes into the cell nucleus which are normally in inactivated form. As known, small interference RNA and micro RNA’s regulate the gene function in the cell. These molecules are generally transfected to eukaryote cells for gene silencing by using viral and non-viral transfection methodologies. Gene silencing technology is an important tool to drive induced pluripotent stem cell into a desired pathway becoming a differentiated neuronal cell, a pancreatic cell or a cardiac cell. These improvements may represent us a possibility of regeneration therapy applications in the future. This technology may provide us tissue and organ requirement in personal based conditions.
Keywords: Embriyonal stem cell, induced pluripotent stem cell, si RNA, mi RNA, regenerative medicine, gene transfection
Anahtar Kelimeler
Embriyonal stem cell induced pluripotent stem cell si RNA mi RNA regenerative medicine gene transfection
Kaynakça
- Verfaillie CM, Pera MF, Lansdorp PM. Stem cells: hype and reality. Hematology Am Soc Hematol Educ Program 2002: 369-91.
- Ogawa M. Differentiation and proliferation of hematopoietic stem cells. Blood 1993; 81: 2844-53.
- Banerjee P, Crawford L, Samuelson E, Feuer G. Hematopoietic stem cells and retroviral infection. Retrovirology 2010; 7: 8.
- Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-7.
- Stewart R, Yang C, Anyfantis G, Przyborski S, Hole N, Strachan T, Stojkovic M, Keith WN, Armstrong L, Lako M. Silencing of the expression of pluripotent driven-reporter genes stably transfected into human pluripotent cells. Regen Med 2008; 3: 505-22.
- Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 66376
- Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-72.
- Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-11.
- Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003; 3: 895-902.
- Haim S, Mitelman F. Cancer Cytogenetics, chromosomal and molecular genetic aberrations of the tumor cells. Wiley Blackwell Publications. 3 th ed. New Jersey 200 Takada T, Nemoto K, Yamashita A, Kato M, Kondo Y, Torii R. Efficient gene silencing and cell differentiation using siRNA in mouse and monkey ES cells. Biochem Biophys Res Commun 2005; 331: 1039-44.
- Mancheño-Corvo P, Martín-Duque P. Viral gene therapy. Clin Transl Oncol 2006; 8: 858-67.
- Ko BS, Chang TC, Shyue SK, Chen YC, Liou JY. An efficient transfection method for mouse embryonic stem cells. Gene Therapy 2009; 16: 154-8. Güran Ş. Kalp yetmezliğinde anjiyogenezis ve gen tedavisi. Gülhane Tıp Dergisi 2004; 46: 84-7.
- Lakshmipathy U, Pelacho B, Sudo K, Linehan JL, Coucouvanis E, Kaufman DS, Verfaillie CM. Efficient transfection of embryonic and adult stem cells. Stem Cells 2004; 22: 531-43.
- Matin MM, Walsh JR, Gokhale PJ, Draper JS, Bahrami AR, Morton I, Moore HD, Andrews PW. Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells 2004; 22: 659-68.
- Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M. Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells 2005; 23: 1035-43.
- Velkey JM, O'Shea KS. Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. Genesis 2003; 37: 18-24. Prakash S, Khan A, Paul A. Nanoscaffold based stem cell regeneration therapy: recent advancement and future potential. Expert Opin Biol Ther 2010; 10: 16496
- Hemmat S, Lieberman DM, Most SP. An introduction to stem cell biology. Facial Plast Surg 2010; 26: 343-9.
- Poss KD. Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat Rev Genet 2010; 11: 710-22.
Öz
SUMMARY Human stem cell is a kind of special cell type which has self renewal capasity and differentiation potential. Embriyonic stem cells are an invaluable tool for stem cell biology and regenerative medicine as they have the capacity to differentiate into various functional cells. With the new gene technologies improved in recent years, it is possible to transfer a gene into a eukaryote cell. A desired gene can be activated or silenced via these technologies. In an appropriate condition, a differentiated human cell can be transformed into an embryonic stem cell like type (induced pluripotent stem cell) by transforming the active form of some genes into the cell nucleus which are normally in inactivated form. As known, small interference RNA and micro RNA’s regulate the gene function in the cell. These molecules are generally transfected to eukaryote cells for gene silencing by using viral and non-viral transfection medhodologies. Gene silencing technology is an important tool to drive an embryonic stem cel or induced pluripotent stem cell into a desired pathway becoming a differentiated neuronal cell, a pancreatic cell or a cardiac cell. These improvements may represent us a possibility of regeneration therapy applications in the future. This technology may provide us tissue and organ requirement in personal based conditions.
Anahtar Kelimeler
Embriyonal kök hücre indüklenmiş pluripotent kök hücre si RNA mi RNA rejeneratif tıp gen transferi
Kaynakça
- Verfaillie CM, Pera MF, Lansdorp PM. Stem cells: hype and reality. Hematology Am Soc Hematol Educ Program 2002: 369-91.
- Ogawa M. Differentiation and proliferation of hematopoietic stem cells. Blood 1993; 81: 2844-53.
- Banerjee P, Crawford L, Samuelson E, Feuer G. Hematopoietic stem cells and retroviral infection. Retrovirology 2010; 7: 8.
- Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM. Embryonic stem cell lines derived from human blastocysts. Science 1998; 282: 1145-7.
- Stewart R, Yang C, Anyfantis G, Przyborski S, Hole N, Strachan T, Stojkovic M, Keith WN, Armstrong L, Lako M. Silencing of the expression of pluripotent driven-reporter genes stably transfected into human pluripotent cells. Regen Med 2008; 3: 505-22.
- Takahashi K, Yamanaka S. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 2006; 126: 66376
- Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 2007; 131: 861-72.
- Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2001; 414: 105-11.
- Pardal R, Clarke MF, Morrison SJ. Applying the principles of stem-cell biology to cancer. Nat Rev Cancer 2003; 3: 895-902.
- Haim S, Mitelman F. Cancer Cytogenetics, chromosomal and molecular genetic aberrations of the tumor cells. Wiley Blackwell Publications. 3 th ed. New Jersey 200 Takada T, Nemoto K, Yamashita A, Kato M, Kondo Y, Torii R. Efficient gene silencing and cell differentiation using siRNA in mouse and monkey ES cells. Biochem Biophys Res Commun 2005; 331: 1039-44.
- Mancheño-Corvo P, Martín-Duque P. Viral gene therapy. Clin Transl Oncol 2006; 8: 858-67.
- Ko BS, Chang TC, Shyue SK, Chen YC, Liou JY. An efficient transfection method for mouse embryonic stem cells. Gene Therapy 2009; 16: 154-8. Güran Ş. Kalp yetmezliğinde anjiyogenezis ve gen tedavisi. Gülhane Tıp Dergisi 2004; 46: 84-7.
- Lakshmipathy U, Pelacho B, Sudo K, Linehan JL, Coucouvanis E, Kaufman DS, Verfaillie CM. Efficient transfection of embryonic and adult stem cells. Stem Cells 2004; 22: 531-43.
- Matin MM, Walsh JR, Gokhale PJ, Draper JS, Bahrami AR, Morton I, Moore HD, Andrews PW. Specific knockdown of Oct4 and beta2-microglobulin expression by RNA interference in human embryonic stem cells and embryonic carcinoma cells. Stem Cells 2004; 22: 659-68.
- Hyslop L, Stojkovic M, Armstrong L, Walter T, Stojkovic P, Przyborski S, Herbert M, Murdoch A, Strachan T, Lako M. Downregulation of NANOG induces differentiation of human embryonic stem cells to extraembryonic lineages. Stem Cells 2005; 23: 1035-43.
- Velkey JM, O'Shea KS. Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. Genesis 2003; 37: 18-24. Prakash S, Khan A, Paul A. Nanoscaffold based stem cell regeneration therapy: recent advancement and future potential. Expert Opin Biol Ther 2010; 10: 16496
- Hemmat S, Lieberman DM, Most SP. An introduction to stem cell biology. Facial Plast Surg 2010; 26: 343-9.
- Poss KD. Advances in understanding tissue regenerative capacity and mechanisms in animals. Nat Rev Genet 2010; 11: 710-22.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Bölüm | Derlemeler |
| Yazarlar | |
| Yayımlanma Tarihi | 22 Mart 2013 |
| Yayımlandığı Sayı | Yıl 2013Cilt: 35 Sayı: 1 |