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PENDAHULUAN
Pada dekade terakhir perhatian dan penelitian dalam bidang sel punca (stem cells)
mengalami kemajuan yang amat pesat. Para peneliti menggunakan sel punca untuk mengetahui
dan mempelajari proses pertumbuhan dan perkembangan jaringan tubuh manusia serta
patogenesis penyakit-penyakit yang diderita. Disamping itu penggunaan sel punca dalam
perngobatan penyakit-penyakit yang sudah tidak mungkin untuk diobati lagi baik secara
konservatif maupun operatif khususnya penyakit degeneratif maupun kelainan lainnya seperti
trauma, keganasan dan sebagainya juga meningkat pesat. Dalam bidang farmakologi para peneliti
juga menggunakan sel punca untuk menguji obat-obat baru. Tentu saja penggunaan sel punca
dalam bidang penelitian dan pengobatan penyakit ini tidak terlepas dari potensi nilai bisnis yang
akan diraih manakala sel punca ini sudah dapat digunakan untuk mengobati penyakit-penyakit
atau kelainan-kelainan pada manusia.
Penggunaan dan pengembangan sel punca dalam bidang penelitian dan aplikasinya
diklinik dalam rangka mengobati penyakit tidak terlepas dari masalah etik yang mungkin
membayanginya, khususnya penggunaan dan pemanfaatan sel punca yang berasal dari embrio
(embryonic stem cells). Tanggal 12 Pebruari 2004 sejumlah peneliti di Korea telah
mengumumkan pembuatan stem cell manusia pertama dengan cara transplantasi sel somatik.
Walaupun pernyataan ini kemudian ditarik kembali dengan alasan manipulasi data atau perilaku
tidak etis para penelitinya, hal ini telah mendorong para peneliti untuk menggiatkan penelitian sel
punca dan pengkolnan embrio guna pemakaian dalam pengobatan penyakit-penyakit degeneratif.
_______________________________________________________________________
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** Dipresentasikan pada diskusi panel Realitas baru dan prospek perkembangan seputar terapi sel punca
(stem cell), R. Rapat PB IDI, Jakarta, Sabtu 24 Mei 2008
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 2
Penelitian dengan menggunakan embrio dan pengklonan embrio telah menyulut kontroversi dan
menjadi bahan perdebatan dibanyak negara, seperti Inggris, Amerika Serikat, Swedia dan
sebagainya.
Uraian dibawah ini akan membahas tentang pengertian, aspek biomedik dan potensi
penggunaannya di klinik serta masalah etik yang membayanginya
DEFINISI
Sel Punca atau stem cell adalah sel yang tidak/belum terspesialisasi dan
mempunyai kemampuan/potensi untuk berkembang menjadi berbagai jenis sel-sel yang
spesifik yang membentuk berbagai jaringan tubuh.
2. Pluripoten yaitu sel punca yang dapat berdifferensiasi menjadi 3 lapisan germinal
(ektoderm, mesoderm, dan endoderm) tetapi tidak dapat menjadi jaringan
ekstraembrionik seperti plasenta dan tali pusat. Yang termasuk sel punca pluripoten
adalah sel punca embrionik (embryonic stem cells).
3. Multipoten yaitu sel punca yang dapat berdifferensiasi menjadi berbagai jenis sel
misalnya sel punca hemopoetik (hemopoetic stem cells) yang terdapat pada sumsum
tulang yang mempunyai kemampuan untuk berdifferensiasi menjadi berbagai jenis sel
yang terdapat di dalam darah seperti eritrosit, lekosit dan trombosit. Contoh lainnya
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 4
adalah sel punca saraf (neural stem cells) yang mempunyai kemampuan berdifferensiasi
menjadi sel saraf dan sel glia.
4. Unipotent yaitu sel punca yang hanya dapat berdifferensiasi menjadi 1 jenis sel. Berbeda
dengan non sel punca, sel punca mempunyai sifat masih dapat memperbaharui atau
meregenerasi diri (self-regenerate/self renew) Contohnya erythroid progenitor cells
hanya mampu berdifferensiasi menjadi sel darah merah.
neuron, hepatosit dan sebagainya, sehingga dapat dipakai untuk transplantasi jaringan
yang rusak.
Therapeutic cloning atau disebut Somatic Cell Nuclear Transfer (SCNT) adalah
suatu teknik yang bertujuan untuk menghindari resiko penolakan atau rejeksi. Pada teknik
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 7
ini inti sel telur donor dikeluarkan dan diganti dengan inti sel resipien. Sel yang telah
dimanipulasi ini kemudian akan membelah diri dan setelah menjadi blastokista maka
inner cell massnya akan diambil sebagai embryonic stem cells. Stem cells ini kemudian
akan dimasukkan kembali kedalam tubuh resipien dan stem cells ini kemudian akan
berdifferensiasi menjadi sel organ (sel beta pankreas, sel otot jantung dan lain-lain).
Tanpa reaksi penolakan karena sel tersebut mengandung materi genetik resipien.
sifat self renewing pada stem cell menyebabkan pemberian stem cells yang
mengandung transgen tidak perlu dilakukan berulang-ulang. Selain itu
hematopoetic stem cells juga dapat berdifferensiasi menjadi bermacam-macam sel
sehingga transgen tersebut dapat menetap diberbagai macam sel.
2. Penelitian untuk mempelajari proses-proses biologis yang terjadi pada organisma
termasuk perkembangan organisma dan perkembangan kanker
3. Penelitian untuk menemukan dan mengembangkan obat-obat baru terutama
untuk mengetahui efek obat terhadap berbagai jaringan
4. Terapi sel (cell based therapy)
Stem cell dapat hidup diluar tubuh manusia, misalnya di cawan Petri. Sifat ini
dapat digunakan untuk melakukan manipulasi pada stem cells yang akan
ditransplantasikan ke dalam organ tubuh untuk menangani penyakit-penyakit
tertentu tanpa mengganggu organ tubuh.
Penggunaan sel punca embrionik untuk mengobati cidera pada medula spinalis
(spinal cord)
Cidera pada medula spinalis disertai demielinisasi menyebabkan hilangnya fungsi
neuron. Sel punca dapat mengembalikan fungsi yang hilang dengan cara melakukan
remielinisasi . Percobaan dengan sel punca embrionik tikus dapat menghasilkan
oligodendrosit yang kemudian dapat menyebabkan remielinisasi akson yang rusak
KEPUSTAKAAN
1. McNeish, J. (2004) Embryonic Stem Cells in Drug Discovery Nat. Rev. Drug
Discov. 3, 70-80
2. Davila, J.C., Cezar, G.G., Thiede, M., Strom, S., Miki, T., Trosko J. (2004) Use
and Application of Stem Cells in Toxicology. Toxicol. Sci. 79, 214-223
3. The stem Cell- Stem cell information- The Official national Institute of Health
Resource for Stem Cell Research .
4. Anatomy 101: Stem cell-Reeve Irvine Research Center- http/
www.reeve.uci.edu/anatomy/stem cells.php.
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 12
5. Sell, S. (2004) Stem cells. Stem Cell Handbook ed. by Sell, S. 1-18.
6. FOXNews.com - New Stem-Cell Procedure Doesn't Harm Embryos, Company
Claims - Biology | Astronomy | Chemistry | Physics
7. Therapeutic use of cell nuclear replacement: Therapeutic cloning-Research in
focus- MRC (Medical Research Council)
8. For review: Floss,T., Wurst, W. (2002) Functional Genomics by Gene-trapping in
ES cells. Embryonic Stem Cells Methods and Protocols ed. by Turksen, K. 347-
379
9. What are stem eclls? – CSA guide to discovery – http://www.csa.com/discovery
guide/stem cell//overview.php
10. Liu S, Qu Y, Stewart TJ et al. Embryonic stem cells differentiate into
oligodendrocyts and myelinated in culture and after spinal cord transplantation.
PNAS 2000: 97(11):6126-6131
11. Li Y, Chen J, Chen XG, et al. Human marrow stromal cell therapy for stroke in
rat: neurotrophins and functional recovery Neurology 2002;59:514 –523
12. Zhao LR, Duan WM, Reyes M, et al. Human bone marrow stem cells exhibit
neural phenotypes and ameliorate neurological deficits after grafting into the
ischemic brain of rats. ExpNeurol 2002;174:11–20)
13. Bartinek J, Vanderheyden M, Vandekerchove B et al., Intracoronary injection of
CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery
after recent myocardial infarction. Circulation 2005; 112 (9 suppl): 78-83
14. Stem cells transplantation in myocard infarction: A status report- Ann Intern.
Med. 2004 May: 140(9): 729-737
15. Setiawan B, Aplikasi teraupetik sel stem embrionik pada berbagai penyakit
degeneratif. Cermin Dunia Kedokteran 2006; 153: 5-8
16. Tadjudin MK, Aspek bioetika penelitin stem cell. Cermin Dunia Kedokteran
2006; 153: 9-12.
17. Kaligis RWM, Aplikasi terapi stem cell pada infark miokard akut. Cermin Dunia
Kedokteran 2006; 153: 13
18. Reksodiputro AH, Stem cell therapy in hematologic malignancies. Cermin Dunia
Kedoketran 2006; 153: 14-15
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 13
ES cells from mouse embryos have been cultured since the 1980s by various groups of
researchers working independently.10 These pioneers established murine embryonic stem
cells lines that could differentiate into several different cell types.11 ES cell lines have
been established from other mammals (hamsters, rats, pigs, and cows). Thompson and
colleagues at the University of Wisconsin reported isolation of primate ES cells in 1995
and human ES cells in 1998.12
What are the uses of Cultured Stem cells? The most prominent is cell therapy for treating
conditions such as spinal cord injuries and for curing disease. Stem cells are used to
investigate questions to further basic and clinical research. Here are the major
applications to date:
types from all three germ layers. The desired cells are isolated and cultured and
the differentiated cells are then used for therapy. ES cells have been induced to
differentiate into neurons, cardiomyocytes and endoderm cells.
back to article
12. Thompson, J.A., Kalishman, J., Golos, T.G., Durning, M., Harris, C.P., Becker,
R.A., Hearn, J.P. (1995) Isolation of a Primate Embryonic Stem Cell Line. Proc.
Natl. Acad. Sci. USA 86, 7844-7848; Thomson, J.A, Itskovitz-Eldor, J., Shapiro,
S.S., Waknitz, M.A., Swiergiel, J.J., Marshal, V.S., Jones, J.M. (1998) Embryonic
Stem Cell Lines Derived from Human Blastocysts. Science 282, 1145-1147.
13. Amit, M., Segev, H., Manor, D., Itskovitz-Eldor, J. (2003) Subcloning and
Alternative Methods for the Derivation and Culture of Human Embryonic Stem
Cells. Human Embyronic Stem Cells ed. by Chiu, M., Rao, M.S. 127-141.
14. Carpenter, M.K., Xu, C., Daigh, C.A., Antosiewicz, J.E., Thomson, J.A. (2003)
Protocols for the Isolation and Maintenance of Human Embryonic Stem Cells.
Human Embyronic Stem Cells ed. by Chiu, M., Rao, M.S.
15. Drukker M., Benvenisty, N. (2003) Genetic Manipulation of Human Embryonic
Stem Cells. Human Embryonic Stem Cells ed. by Chiu, A.Y., Rao, M.S. 265-284.
back to article
16. Shamblott, M.J., Axelman, J., Wang, S., Bugg, E.M., Littlefield, J.W., Donovan,
P.J., Blumenthal, P.D., Huggins, G. R., Gearhart J.D., (1998) Derivation of
Pluripotent Stem Cells from Cultured Human Primordial Germ CellS. Proc. Natl.
Acad. Sci.USA 95, 13726-13731.
17. Doyonnas, R., Blau, H.M. (2004) What is the Future of Stem Cell Research?
Stem Cell Handbook ed. by Sell, S. 491-499.
18. Draper, J.S. Moore, H., Andrews, P.W. (2003) Embryonal Carcinoma Cells.
Human Embryonic Stem Cells ed. Chiu, A. Y., Rao, M.S. 63-87.
19. Adult Stem Cells ed. Turksen, K. (2004) For reviews of hematopoietic stem cells:
http://stemcells.nih.gov/info/scireport/chapter5.asp;
http://www.stemcell.com/technical/Hema%20SC%20MiniReview.pdf; for
mesenchymal stem cells: http://www.stemcell.com/technical/MSC
%20MiniReview.pdf; for neural stem cells:
http://www.stemcell.com/technical/Neurocult%20MiniReview.pdf
20. Nosrat, I.V., Smith, C. A., Mullally, P., Olson, L., Nosrat C.A. (2004) Dental Pulp
Cells Provide Neurotrophic Support for Dopaminergic Neurons and Differentiate
into Neurons in vitro; implications for Tissue Engineering and Repair in the
Nervous System. Eur. J. of Neurosci. 19, 2388-2398.
back to article
21. Shen, C-N., Horb, M.E., Slack, J.M.W., Tosh,D. (2003) Transdifferentiation of
Pancreas to Liver. Mech. Dev.120, 107-116.
22. Priller, J. (2004) From Marrow to Brain. Adult Stem Cells ed. by Turksen, K.
215-233.
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 17
23. de Wynter, E.A. (2003) What is the future of Cord blood stem cells? Cytotech.
41, 133-138.
24. Gossler, A., Doetschman, T.C., Eistattaer, H., Katz, M., Schmidt, W., Kemler, R.
(1986) Transgenesis by means of Blastocyst Derived Embryonic Stem Cell Lines.
Proc. Natl. Acad. Sci. USA 83, 9065-9069.
25. Thomas, K.R., Capecchi, M.R. (1987) Site-directed Mutagenesis by Gene
Targeting in Mouse Embryo-derived Stem Cells. Cell 51, 503-512.; Koller, B.H.,
Hageman, L.J., Doetschman, T.C., Hagaman, J.R., Huang, S., Williams, P.J., et.
al. (1989) Proc. Natl. Acad. Sci. USA 86, 8924-8931.
back to article
back to article
31. Barker, R.A., Jain, M., Armstrong, R.J.E., Caldwell, M.A. (2003) Stem Cells and
Neurological Disease. J. Neurol. Neurosurg. Psychiat. 74, 553-557.
32. http://www.who.int/cardiovascular_diseases/resources/atlas/en/
33. Jackson, K.A., Goodell, M.A. (2004) Generation and Stem Cell Repair of Cardiac
Tissue. Stem Cell Handbook, edited by Sell, S. 259-266.
34. Kehat, I., Khimovich, L., Caspi, O., Gepstein, A., Shofti, R., Arbel, G., Huber, I.,
Satin, J., Itskovitz-Eldor, J., Gepstein, L. (2004) Electromechanical Integration of
Cardiomyocytes Derived from Human Embryonic Stem Cells . Nature
Biotechnol. 22, 1282-1289.
35. Fraser, J.K., Schreiber, R.E., Zuk, P.A., Hedrick, M.H. (2004) Adult Stem Cell
Therapy for the Heart. Intl. J. Biochem. Cell Biol. 36, 658-666.
back to article
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 18
36. Cohen, S., Leor, J. (2004) Rebuilding Broken Hearts. Scientific American Nov.
2004, 45-51.
37. http://stemcells.nih.gov/info/scireport/chapter7.asp; Street, C.N., Sipione, S.,
Helms, L., Binette, T., Rajotte, R.V., Bleackley, R.C., Korbutt, G.S. (2004) Stem
Cell-based Approaches to Solving the Problem of Tissue Supply for Islet
Transplantation in Type I Diabetes. Intl. J. Biochem. Cell Biol. 36, 667-683.
38. Bouwens, L. (2004) Islet Cells. Stem Cell Handbook ed. by Sell, S. 429-438.
39. Seaberg, R.M., Smukler, S.R., Kieeffer, T.J., Enikolopov, G., Asghar, Z., Wheeler
M.B., Korbutt, G., van der Kooy, D. (2004) Clonal Identification of Multipotent
Precursors from Adult Mouse Pancreas that Generate Neural and Pancreatic
Lineages. Nat. Biotechnol. 22, 1115-1124.; SeNakajima-Nagata, N., Sakurai, T.,
Mitaka, T., Katakai, T., Yamaot, E., Miyazaki, J., Tabata, Y., Sugai, M., Shimzu,
A.. (2004) In vitro Induction of Adult Hepatic Progenitor Cells into Insulin-
producing Cells. Biochem. Biophys. Res. Commun. 318, 625-630.
40. http://www.parkinson.org/site/pp.asp?c=9dJFJLPwB&b=71125
back to article
41. http://stemcells.nih.gov/info/scireport/chapter8.asp
42. Baier, P.C., Schindehutte HJ., Thinane, K., Flugge G., Fuchs, E., Mansouri, A.,
Paulus, W., Gruss, P.,Trenwalder, C.(2004) Behavioral Changes in Unilaterally 6-
Hydroxy-Dopamine Lesioned Rats after Transplantation of Differentiated Mouse
Embryonic Stem Cells without Morphological Integration. Stem Cells 22, 396-
404.
43. Lindvall O., Bjorklund, A. (2004) Cell Therapy in Parkinson's Disease. NeuroRx.
1, 382-393.
44. Zheng, X., Cai, J., Chen, J., Luo, Y., Zhi-Bing Y., Fotter, E., Wang, Y., Harvey,
B., Miura, T., Backman, C., Chen, G-J., Rao, M.S., Freed. W.J. (2004)
Dopaminergic Differentiation of Human Embryonic Stem Cells. Stem Cells 22,
925-940; Wilmut, I., Paterson, L.A. (2004) Stem cells and Cloning. Stem Cell
Handbook ed. by Sell, S. 75-80.
Barker, R.A., Widner, H. (2004). Immune Problems in the Central Nervous System Cell
Therapy. NeuroRx. 1, 472-481.
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 19
Embryonic stem cells (ES cells) were first derived from mouse embryos in 1981 by
Martin Evans and Matthew Kaufman and independently by Gail R. Martin. Gail R.
Martin is credited with coining the term 'Embryonic Stem Cell'.[3][4] A breakthrough in
human embryonic stem cell research came in November 1998 when a group led by James
Thomson at the University of Wisconsin-Madison first developed a technique to isolate
and grow the cells when derived from human blastocysts.[5]
On August 23, 2006, the online edition of Nature scientific journal published a letter by
Dr. Robert Lanza (medical director of Advanced Cell Technology in Worcester, MA)
stating that his team had found a way to extract embryonic stem cells without destroying
the actual embryo.[9] This technical achievement would potentially enable scientists to
work with new lines of embryonic stem cells derived using public funding. Federal
funding is currently limited to research using embryonic stem cell lines derived prior to
August 2001.
Professor Yamanaka had a recent breakthrough[10] in which the skin cells of laboratory
mice were genetically manipulated back to their embryonic state. This work was
confirmed by two other groups, demonstrating that the addition of just 4 genes (Oct3/4,
Sox2, Klf4, and c-Myc) could reprogram mouse skin cells into embryonic stem like cells.
The ability to reproduce such findings are very important in science and the stem cell
field, especially after Hwang Woo-Suk from Korea fabricated data, claiming to have
generated human ES cells from cloned embryos. These cells produced by Yamanaka as
well as the other laboratories demonstrated all the hallmarks of embryonic stem cells
including the ability to form chimeric mice and contribute to the germ-line. One issue
with this work is that the mice generated from these ES lines were prone to develop
cancer due to the use of Myc, which is a known oncogene.
On 20th of November, 2007, two research teams, one of which was headed by Professor
Yamanaka and the other by James Thomson[11] announced a similar breakthrough with
ordinary human skin cells that were transformed into batches of cells that look and act
like embryonic stem cells. This may enable the generation of patient specific ES cell lines
that could potentially be used for cell replacement therapies. In addition, this will allow
the generation of ES cell lines from patients with a variety of genetic diseases and will
provide invaluable models to study those diseases.
While this work is a huge accomplishment for science, there is still much work to be
done before this technology can be used for the treatments of disease. First, the genes
used to reprogram the skin cells into ES-like cells were added by the use of retroviruses
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 20
that can cause mutations and lead to the risk of possible cancers, although recent research
by professor Yamanaka's research group has made advances in avoiding this particular
problem.[12]
In addition, as shown with the mouse work, one of the genes used to reprogram, Myc, can
also cause cancer. The group led by Thomson did not use Myc to reprogram and may not
have this difficulty. Future work is aimed at attempting to reprogram without permanent
genetic manipulation of the cells with viruses. This could be accomplished by either
small molecules or other methodologies to express these reprogramming genes.
However, as a first indication that the induced pluripotent stem (iPS) cell technology can
in rapid succession lead to new cures, it was used by a research team headed by Rudolf
Jaenisch of the Whitehead Institute for Biomedical Research in Cambridge,
Massachusetts, to cure mice of sickle cell anemia, as reported by Science journal's online
edition on 6th of December.[13]
On January 16, 2008, a California based company, Stemagen, announced that they had
created the first mature cloned human embryos from single skin cells taken from adults.
These embryos can be harvested for patient matching embryonic stem cells.[14]
1. ^ Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto
University, Kyoto (August 25, 2006). "Induction of Pluripotent Stem Cells from Mouse
Embryonic and Adult Fibroblast Cultures by Defined Factors". Cell.
2. ^ Andrews P, Matin M, Bahrami A, Damjanov I, Gokhale P, Draper J (2005).
"Embryonic stem (ES) cells and embryonal carcinoma (EC) cells: opposite sides of the
same coin.". Biochem Soc Trans 33 (Pt 6): 1526-30. PMID 16246161.
3. ^ Evans M, Kaufman M (1981). "Establishment in culture of pluripotential cells from
mouse embryos.". Nature 292 (5819): 154-6. doi:10.1038/292154a0. PMID 7242681.
4. ^ Martin G (1981). "Isolation of a pluripotent cell line from early mouse embryos
cultured in medium conditioned by teratocarcinoma stem cells.". Proc Natl Acad Sci U S
A 78 (12): 7634-8. doi:10.1073/pnas.78.12.7634. PMID 6950406.
5. ^ Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V, Jones J
(1998). "Embryonic stem cell lines derived from human blastocysts.". Science 282
(5391): 1145-7. doi:10.1126/science.282.5391.1145. PMID 9804556.
6. ^ "Derivation of embryonic germ cells and male gametes from embryonic stem cells"
(January 8, 2004). Nature 427: 148-154. doi:10.1038/nature02247.
7. ^ Access to articles : Nature Medicine
8. ^ Lancet Medical Journal
9. ^ Klimanskaya I, Chung Y, Becker S, Lu SJ, Lanza R. (2006). "Human embryonic stem
cell lines derived from single blastomeres.". Nature 444 (7118): 481-5. PMID 16929302.
10. ^ "Human stem cells may be produced without embryos ‘within months’", Zangani, July
17, 2007.
11. ^ "Embryonic stem cells made without embryos", Reuters, November 21, 2007.
12. ^ "Researchers get closer to safe stem cell treatments", AFP, February 14, 2008.
13. ^ Rick Weiss. "Scientists Cure Mice Of Sickle Cell Using Stem Cell Technique: New
Approach Is From Skin, Not Embryos", Washington Post, December 7, 2007, pp. A02.
14. ^ Helen Briggs. "US team makes embryo clone of men", BBC, January 17, 2008,
pp. A01.
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 21
Embryonic stem cell lines (ES cell lines) are cultures of cells derived from the epiblast
tissue of the inner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[6] A
blastocyst is an early stage embryo—approximately four to five days old in humans and
consisting of 50–150 cells.
Nearly all research to date has taken place using mouse embryonic stem cells (mES) or
human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet
they require very different environments in order to maintain an undifferentiated state.
Mouse ES cells are grown on a layer of gelatin and require the presence of Leukemia
Inhibitory Factor (LIF).[7] Human ES cells are grown on a feeder layer of mouse
embryonic fibroblasts (MEFs) and require the presence of basic Fibroblast Growth Factor
(bFGF or FGF-2).[8] Without optimal culture conditions or genetic manipulation,[9]
embryonic stem cells will rapidly differentiate.
A human embryonic stem cell is also defined by the presence of several transcription
factors and cell surface proteins. The transcription factors Oct-4, Nanog, and SOX2 form
the core regulatory network that ensures the suppression of genes that lead to
differentiation and the maintenance of pluripotency.[10] The cell surface antigens most
commonly used to identify hES cells are the glycolipids SSEA3 and SSEA4 and the
keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell
includes many more proteins and continues to be a topic of research.[11]
The signals that lead to reprogramming of cells to an embryonic-like state are also being
investigated. These signal pathways include several transcription factors including the
oncogene c-Myc. Initial studies indicate that transformation of mice cells with a
combination of these anti-differentiation signals can reverse differentiation and may
allow adult cells to become pluripotent.[24] However, the need to transform these cells
with an oncogene may prevent the use of this approach in therapy.
There exists a widespread controversy over human embryonic stem cell research that
emanates from the techniques used in the creation and usage of stem cells. Human
Aspek Dasar Sel Punca Embrionik (Embryonic Stem Cells) dan Potensi Pengembangannya 22
embryonic stem cell research is controversial because, with the present state of
technology, starting a stem cell line requires the destruction of a human embryo and/or
therapeutic cloning. However, recently, it has been shown in principle that embryonic
stem cell lines can be generated using a single-cell biopsy similar to that used in
preimplantation genetic diagnosis that may allow stem cell creation without embryonic
destruction.[29] It is not the entire field of stem cell research, but the specific field of
human embryonic stem cell research that is at the centre of an ethical debate.
Opponents of the research argue that embryonic stem cell technologies are a slippery
slope to reproductive cloning and can fundamentally devalue human life. Those in the
pro-life movement argue that a human embryo is a human life and is therefore entitled to
protection.
Contrarily, supporters of embryonic stem cell research argue that such research should be
pursued because the resultant treatments could have significant medical potential. It is
also noted that excess embryos created for in vitro fertilisation could be donated with
consent and used for the research.
The ensuing debate has prompted authorities around the world to seek regulatory
frameworks and highlighted the fact that stem cell research represents a social and ethical
challenge.
• 1960s - Joseph Altman and Gopal Das present scientific evidence of adult
neurogenesis, ongoing stem cell activity in the brain; their reports contradict
Cajal's "no new neurons" dogma and are largely ignored.
• 1963 - McCulloch and Till illustrate the presence of self-renewing cells in mouse
bone marrow.
• 1968 - Bone marrow transplant between two siblings successfully treats SCID.
• 1978 - Haematopoietic stem cells are discovered in human cord blood.
• 1981 - Mouse embryonic stem cells are derived from the inner cell mass by
scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is
attributed for coining the term "Embryonic Stem Cell".
• 1992 - Neural stem cells are cultured in vitro as neurospheres.
• 1997 - Leukemia is shown to originate from a haematopoietic stem cell, the first
direct evidence for cancer stem cells.
• 1998 - James Thomson and coworkers derive the first human embryonic stem cell
line at the University of Wisconsin-Madison.
• 2000s - Several reports of adult stem cell plasticity are published.
• 2001 - Scientists at Advanced Cell Technology clone first early (four- to six-cell
stage) human embryos for the purpose of generating embryonic stem cells.[30]
• 2003 - Dr. Songtao Shi of NIH discovers new source of adult stem cells in
children's primary teeth.[31]
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