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6. Rekonstruksi Cartilago yang rusak dengan Stem Sel

REKONTRUKSI CARTILAGO YANG RUSAK DENGAN STEM SEL

Oleh Dr H Subagyo SpB - SpOT

 

Secara alamiah mahluk hidup telah dibekali dengan berbagai macam kemampuan untuk mempertahankan diri.Hal ini termasuk pula kemampuan dalam meregenerasikan bagian tubuhyang secara terus-menerus perlu diperbaharui, misalnya pada saat kulit terkelupas, sel-sel darah merah yang rusak. Tugas pembaharuan sel - sel ini diemban oleh stem sel; oleh karena itu stem sel memiliki peran vital dalam perkembangan, pertumbuhan, kelangsungan, dan perbaikan semua jaringan yang hidup termasuk otak, tulang, otot, saraf, darah, kulit, dan organ lainnya.

 

Gambar dari stem sel.

Sumber :http://www.odec.ca/projects/2004/mcgo4s0/public_html/t5/stem_cell.jpg

Akhir - akhir ini sering disinggung pengembangan stem sel dalam berbagai aspek terapi penyakit, baik penyakit keganasan, hematologi maupun penyakit degeneratif. Dalam laboratorium telah banyak dilakukan berbagai cara untuk memodifikasi sel ini sehingga dapat disimpan, diperbanyak, didiferensiasikan, bahkan dibuat agar menjadi suatu organ yang spesifik. Begitu pesat kemajuan di bidang pengembangan stem sel, sehingga seringkali kita dihadapkan pada pertanyaan - pertanyaan menggelitik mengenai apa sebetulnya stem sel itu.

DEFINISI STEM SEL

Stem sel adalah suatu jenis sel yang terdapat di dalam tubuh mahluk hidup, termasuk juga manusia. Stem sel tidak mempunyai fungsi spesifik seperti sel pada umumnya, tetapi pada saat dibutuhkan, stem sel dapat mengalami perubahan menjadi sel yang terspesialisasi. Faktor-faktor yang dapat mempengaruhi proses ini adalah berbagai mediator (termasuk juga sitokin dan faktor pertumbuhan) yang dilepaskan oleh sel pada saat mengalami kerusakan atau pada saat jaringan mengalami iskemi.

Stem sel mempunyai 2 sifat:

1. Kemampuan untuk berdiferensiasi menjadi sel lain (differentiate).

Dalam hal ini stem sel mampu berkembang menjadi berbagai jenis sel matang, misalnya sel saraf, sel otot jantung, sel otot rangka, sel pankreas, dan lain-lain.

2. Kemampuan untuk memperbaharui atau meregenerasi dirinya sendiri (self-regenerate/self-renew).

Dalam hal ini stem sel dapat membuat salinan sel yang persis sama dengan dirinya melalui pembelahan sel.

Berdasarkan kemampuan berdiferensiasi, stem sel dibagi menjadi:

1.      Totipotent.

Dapat berdiferensiasi menjadi semua jenis sel. Yang termasuk dalam stem sel totipotent adalah zigot (telur yang telah dibuahi).

2.      Pluripotent.

Dapat berdiferensiasi menjadi 3 lapisan germinal yaitu ektoderm, mesoderm, dan endoderm, tapi tidak dapat menjadi jaringan ekstraembrionik seperti plasenta dan tali pusat. Yang termasuk stem sel pluripotent adalah embryonic stem cells.

3.      Multipotent.

Dapat berdiferensiasi menjadi banyak jenis sel. Misalnya: hematopoietic stem cells.

 

Gambar dari totipotent, pluripotent, dan multipotent.

Sumber :http://www.nature.com/nrm/journal/v6/n9/images/nrm1713-f1.jpg

 

  1. 4.      Unipotent

Hanya dapat menghasilkan 1 jenis sel. Tapi berbeda dengan non-stem cell, stem cell unipoten mempunyai sifat dapat memperbaharui atau meregenerasi diri (self-regenerate/self-renew)

 

Gambar dari unipotent.

Sumber :http://www.allthingsstemcell.com/wp-content/uploads/2009/07/Unipotent-copy.png

 

Berdasarkan Sumbernya stem sel dapat ditemukan dalam berbagai jaringan tubuh, maka dari itu berdasarkan sumbernya, stem sel dibagi menjadi:

  1. Zygote.

Yaitu pada tahap sesaat setelah sperma bertemudengan sel telur.

 

Gambar dari zygote.

Sumber :http://www.blueridgeobg.com/images/zygote.jpg

  1. Embryonic stem cell.

Diambil dari inner cell mass darisuatu blastocyst (embrio yang terdiri dari 50  150 sel,kira-kira hari ke-5 pasca pembuahan).

1. Fetus :Dapat diperoleh dari klinik aborsi.

 

Gambar dari fetus.

Sumber :http://www.halalguide.info/wp-content/uploads/2009/05/human_fetus.jpg

2. Stem cell darah tali pusat.

Diambil dari darah plasenta dantali pusat segera setelah bayi lahir. Stem sel dari darah talipusat merupakan jenis hematopoietic stem cell, dan adayang menggolongkan jenis stem sel ini ke dalam adultstem cell.

3. Adult stem cell.

Diambil dari jaringan dewasa

Stem sel dapat bermigrasi menuju ke jaringan tertentu antara lain melalui dilepaskannya molekul SDF-1 oleh jaringan yang mengalami iskemi. Molekul SDF-1 merupakan homing factor yang merupakan ligan molekul CXCR4 yang terdapat pada permukaan stem sel.

Untuk dapat disebut sebagai stem sel, ada beberapa kriteria yang harus terpenuhi yaitu: sel tersebut belum mempunyai fungsi, belum terdiferensiasi, memiliki kemampuan untuk terus membelah dan memperbanyak diri (berproliferasi) menjadi sel yang identik dengan sel asalnya atau dalam suasana yang sesuai dapat berubah (berdiferensiasi) menjadi sel tipe lain dengan fungsi yang spesifik.

SUMBER STEM SEL

 

1.      STEM SEL EMBRIONIK

Adalah sel yang diambil dari hasil sel kultur inner cell mass (ICM) - suatu kumpulan sel yang terletak di satu sisi blastocyst yang berumur 5 hari dan terdiri dari 100 sel. Stem sel ini mempunyai sifat dapat berkembang biak secara terus menerus dalam media kultur optimal dan pada keadaan tertentu dapat diarahkan untuk berdiferensiasi menjadi berbagai sel yang terdiferensiasi.

Embryonic stem cell biasanya didapatkan dari sisa embrio yang tidak dipakai pada IVF (in vitro fertilization). Tapi saat ini telah dikembangkan teknik pengambilan embryonic stem cell yang tidak membahayakan embrio tersebut, sehingga dapat terus hidup dan bertumbuh. Untuk masa depan hal ini mungkin dapat mengurangi kontroversi etis terhadap embryonic stem cell.

Untuk mengisolasi ICM dari dalam kantung blastocoel, lapisan tropoblast perlu terlebih dahulu dilisiskan. Stem sel embrionik mulai banyak digunakan dalam berbagai penelitian pada tahun 1980an, diawali dengan keberhasilan mengisolasi inner cell mass dari blastosit mencit pada tahun 1981 oleh Evans, Kaufman dan Martin.

 

Gambar dari ICM.

Sumber :http://www.boncherry.com/blog/wp-content/uploads/2010/02/stem-cell-cultivation.gif

Mereka berhasil menemukan kondisi kulturin vitro yang dapatmenumbuhkan sel embrionik mencit hingga menghasilkan cell lines (sel yang telah diisolasi dan dikultur secara in vitro dengan tetap mempertahankan sifat-sifat yang dimilikinya). Keberhasilan tersebut kemudian menjadi acuan untuk mengembangkan kultur stem sel embrionik yang berasal dari embrio manusia. Hal ini terealisasi dengan keberhasilan James Thomson mendapatkan 5 cell lines dari sel punca embrionik manusia untuk pertama kalinya pada tahun 1998.

 

Gambar dari James Thomson

Sumber :http://upload.wikimedia.org/wikipedia/commons/thumb/e/e9/JamesThomson(1822-1892).JPG/300px-JamesThomson(1822-1892).JPG

Embrio yang utuh memiliki sifat totipoten yaitu dapat berkembang menjadi suatu individu baru, sedangkan stem sel embrionik disebut memiliki sifat pluripoten yaitu dapat berkembang menjadi sel yang berasal dari 3 galur (ektoderm, mesoderm, dan endoderm). Hal ini hingga saat ini masih membatasi penggunaan stem sel embrionik dalam transplantasi, yaitu kekhawatiran akan terbentuknya teratoma (keganasan yang terdiri dari berbagai tipe jaringan berasal dari galur ectoderm, mesoderm, dan endoderm).

Stem sel embrionik mempunyai kemampuan untuk berproliferasi secara terus menerusdalam kultur optimal dan dalam keadaan tertentu mampu berdiferensiasi menjadi berbagai tipesel jaringan, seperti otot polos, kardiomiosit, neuron, sel beta pankreas, khondrosit, dan sebagainya. Karena sifat ini maka stem sel embrionik ini dapat dipakai untuk mengobati berbagai penyakit degeneratif yang sekarang termasuk dalam bidang kedokteran regeneratif.

 

Gambar dari inner stem cell.

Sumber :http://www.csa.com/discoveryguides/stemcell/images/pluri.jpg

Dalam beberapa tahun lagi stem sel embrionik manusia ini dapat dipakai untuk transplantasi berbagai organ yang rusak, seperti ginjal, hati, jantung, tulang dan sebagainya. Penggunaan stem cell embrionik masih dibayangi oleh berbagai masalah etik dan masih dilarang di beberapa negara seperti di AS, Jerman, dan Perancis, sehingga menghambat kemajuan penelitian. Tetapi di berbagai negara lain seperti, UK, Singapura, Korea, India, dan China, penggunaan sel stem embrionik manusia untuk kedokteran regeneratif diperbolehkan, sehingga penelitian di negara-negara tersebut telah mengalami banyak kemajuan.

Untuk mencegah kontroversi ini, maka alternatif lain adalah menggunakan humanUmbilical Cord Blood (hUBC)yang mengandung banyak adult stem cellsdan mempunyai kemampuan proliferasi lebih baik daripada sel stem sumsum tulang, human Bone Marrow (hBM). Di Indonesia keadaannya masih belum jelas.

 

Gambar dari preparat hUBC.

Sumber :http://www.luvdebbie.com/wp-content/uploads/2007/08/dsc00034.JPG

 1. Stem sel dewasa ( Adult stem cells )

Stem sel yang berada di dalam organ setelah individu dilahirkan, disebut stem sel dewasa. Stem sel tipe ini memiliki kemampuan untuk berdiferensiasi menjadi sel tipe lain tergantung pada daerah tempatnya berada.

Selain terdapat di dalam sumsum tulang dan dalam darah tepi, stem sel terdapat pada setiap bagian tubuh termasuk di dalam organ jantung, liver, ginjal, paru-paru, pulpa gigi, usus, lapisan lemak subkutis, bahkan otak. Namun untuk memperoleh stem sel dalam jumlah banyak, saat ini pengambilan stem sel masih tergantung pada sumber-sumber di bawah ini.


 

Gambar dari stem sell yang berasal dari sum sum tulang belakang.

Sumber :http://www.xcell-center.com/media/7679/stem_cell_specialisation.jpg

a)      Sumsum tulang

Pada umumnya dilakukan aspirasi sumsum tulang pada bagian crista iliaca.

 

Gambar dari aspirasi dari sumsum tulang.

Sumber :http://www.klikdokter.com/userfiles/transp_4.JPG

 b)      Darah tepi

Baik dengan pengambilan darah seperti pada proses donor darah, maupun dengan menggunakan alat apheresis( untuk mengekstrak stem sel dari tubuh ). Dengan pheresis atau apheresis (asal kata dari Greek "aphairesis" yang artinya pengeluaran dari sel - sel), maka darah akan disaring melalui mesin, pada saat itu stem sel akan diambil, dan darah dikembalikan ke dalam sirkulasi. Stem sel kemudian dapat digunakan langsung untuk transplantasi sumsum tulang atau disimpan dalam cairan nitrogen sampai diperlukan.


 

Gambar dari apheresis.

Sumber :http://merumerume.wordpress.com/2010/03/01/stem-cell/

 

Gambar dari apheresis.

Sumber :http://www.omsusa.org/as104.jpg

c)      Darah tali pusat

Diambil melalui v.umbilicalis di bagian tali pusat yang melekat pada plasenta setelah bayi dilahirkan.

 

Gambar dari vena umbilicalis.

Sumber :http://2.bp.blogspot.com/_lvjMrBfb-xk/S43le7aPRzI/AAAAAAAAAF4/d-KG_Y0dOcA/s320/plasenta5.jpg

d)      Lipoaspirat

Limbah sisa liposuction.

 

Gambar dari liposuction.

Sumber :http://www.weightlossforgood.co.uk/images/liposuction.gif

Di luar sumber - sumber di atas, telah banyak dilaporkan berbagai penelitian ilmiah menggunakan stem sel yang berasal dari sumber - sumber lain. Namun hingga kini, sumber - sumber lain tersebut hanya dapat memberikan stem sel dalam jumlah yang sangat terbatas. Sumber-sumber tersebut antara lain adalah:

a)      Darah menstruasi

b)      Pulpa gigi

c)      Jaringan tulang rawan (cartilage)

d)      Jaringan tulang keras (osseous)

e)      Parenkim hepar

f)       Jaringan ventrikel jantung

 

Gambar dari pulpa gigi.

Sumber :http://yayanakhyar.files.wordpress.com/2009/01/tooth-anatomy.jpg

 Dibandingkan stem sel dari sumber lainnya, stem sel darah tali pusat memiliki beberapa kelebihan. Kelebihan tersebut antara lain adalah pengambilannya yang tidak invasif (bahkan apabila tidak dimanfaatkan, darah tali pusat ini seringkali ikut terbuang bersama plasenta), pada penggunaan secara alogenik (donor dan resipien yang berbeda) risiko rejeksi sel punca darah tali pusat lebih rendah dibandingkan dengan stem sel sumsum tulang maupun darah tepi. Lebih lanjut, sel punca darah tali pusat juga dapat disimpan dengan teknik cryopreservation dalam bank darah tali pusat.

 

Gambar dari cryopreservation.

Sumber :http://www.isisrfc.com/images/cryopreservation.jpg

2. Sel stem embrionik maupun sel stem dewasa

Besar potensinya untuk mengobati berbagai penyakit degeneratif, seperti infark jantung, stroke, penyakit Parkinson, diabetes, berbagai macam kanker terutama kanker darah, osteoarthritis dan sebagainya.

 

Gambar dari stem sel embrionik.

Sumber :http://profile.ak.fbcdn.net/object3/1998/9/n45488889814_8386.jpg

Sel stem embrionik sangat elastis dan mudah dikembangkan menjadi berbagai macam jaringan sel, seperti neuron, kardiomiosit, osteoblast, fibroblast dan sebagainya, sehingga dapat dipakai untuk transplantasi jaringan yang rusak. Lagipula immunogenicity nya rendah, selama belum mengalami diferensiasi.

Sel stem dewasa juga bisa dipakai untuk mengobati berbagai penyakit degeneratif, tetapi elastisitasnya sudah berkurang. Mengingat masalah etik, maka banyak negara lebih mengutamakan penelitian pemanfaatan sel stem dewasa pada berbagai penyakit degeneratif, sehingga tidak dihadapkan pada masalah dan kontroversi etika.

Karena sel stem tali pusat (Umbilical cord blood = UCB) mudah didapat dan ternyata banyak mengandung sel stem, maka sekarang banyak diteliti mengenai manfaatnya untuk mengatasi berbagai penyakit degeneratif. Sel stem UCB mudah diperbanyak, immunogenicitynya rendah dan elastisitasnya cukup baik.

 

Gambar dari adult stem cell.

Sumber :http://repairstemcell.files.wordpress.com/2009/02/stem_cell1.jpg

 3. Somatic cell nuclear transfer (SCNT)

Merupakan teknik untuk menghasilkan klon sel stem embrionik yang seratus persen sama seperti donor nukleusnya. Bilamana oosit manusia dikeluarkan nukleusnya (enukleasi) kemudian pada oosit tersebut dimasukkan nukleus somatik dari seorang donor dan kemudian pada oosit tersebut diberi aliran listrik, maka oosit mengalami “reprogramming” DNA, sehingga berkembang biak menjadi embrio.

Keberhasilan SCNT masih sangat rendah dan embrio yang dihasilkan banyak mengalami kelainan kongenital. Tetapi bilamana berhasil maka embrio ini akan merupakan klon dari donor nukleus, sehingga DNA donor nukleus dan embrio seratus persen sama, sehingga jika dilakukan transplantasi tidak akan terjadi penolakan terhadap transplan Teknik SCNT teoretis dapat dipergunakan untuk transplantasi berbagai organ dan jaringan tubuh manusia.

 

Gambar dari SCNT

Sumber :http://magazine.wustl.edu/Spring05/images/p25.gif

 

KELOMPOK STEM SEL

Berdasarkan tipe sel yang dihasilkan, stem sel dapat dikelompokanmenjadi:

  1. Stem sel hematopoetik
  2. Stem sel mesenkimal

TINJAUAN PUSTAKA

STEM SEL HEMATOPOETIK

Stem sel hematopoetik dalam perkembangannya dapat menghasilkan sel pembentuk darah. Sel tipe hematopoetik merupakan tipe sel punca yang sejak lama telah digunakan dalam terapi keganasan darah (leukemia).Strategi terapi ini memungkinkan dilakukannya kemoterapi dosis tinggi yang dapat mengeliminasi sel abnormal (ablasi) pada penderita keganasan.

Populasi sel yang tereliminasi oleh kemoterapi akan digantikan oleh stem sel hematopoetik yang ditransplantasikan. Namun perlu diperhatikan bahwa selama populasi sel belum tergantikan, pasien berada dalam kondisi yang sangat rentan untuk terkena infeksi sehingga diperlukan perawatan di fasilitas “isolasi terbalik” yang dapat menjamin kondisi yang aseptik. Saat ini fasilitas ruang “isolasi terbalik” masih jarang dimiliki oleh rumah sakit di Indonesia dan hal ini seringkali membuat biaya transplantasi stem sel menjadi sangat tinggi.

Stem sel hematopoetik memiliki molekul yang khas pada permukaan selnya, yaitu molekul glikoprotein CD34. Molekul penanda ini dapat digunakan sebagai sarana untuk menghitung jumlah sel punca hematopoetik yang berhasil diisolasi dari berbagai sumber di atas. Bahkan dalam penggunaannya dalam terapi keganasan, telah ditentukan jumlah CD34 yang direkomendasikan oleh ASBMT (American Society for Blood and Marrow Transplantation)

dan ISCT (International Society for Cellular Therapy) bahwa untuk meningkatkan angka keberhasilan engraftment dari sel yang ditransplantasikan diperlukan setidaknya 5 x 106 CD34+ cells/kg berat badan. Oleh karena itu, fasilitas laboratorium terpercaya yang dapat menghitung jumlah sel CD34+ (CD34 enumeration) menjadi mutlak diperlukan untuk transplantasi jenis ini.

 

Gambar dari ASBMT.

Sumber :http://www.nbmtlink.org/images/logos/ASBMT%20Logo.jpg

Dalam beberapa tahun terakhir, dilaporkan bahwa + 80% dari sel punca CD34+ juga mengekspresikan penanda CD133.Sel dalam populasi CD34+/CD133+ dikenal dengan sebutanhemangioblast yang dalam perkembangannya dapat berdiferensiasi menjadi turunan sel hematopoetik (heme) dan sel pembangun pembuluh darah (angio).

Hal ini dipertegas dengan temuan Asahara et al yang melaporkan bahwa populasi sel tersebut merupakan sel tipe Endothelial Progenitor Cell/EPC.Lebih lanjut, EPC merupakansel progenitor yang bertugas meregenerasikan sel endotel dalampembuluh darah .Oleh karena itu, jumlah EPCdalam sirkulasi peredaran darah dilaporkan mengindikasikanbesarnya risiko terjadinya artherosclerosis maupun kejadian cardiovaskular mayor.

STEM SEL MESENKIMAL

Stem sel mesenkimalmerupakan tipe sel punca yang dalamperkembangannya dapat menghasilkan tendon, stromasumsum tulang, tulang rawan, tulang keras, dan sel adiposa. Seltipe ini memiliki sifat khas yaitu tidak memiliki molekul HLA kelasII, sedangkan HLA kelas I hanya diekspresikan dalam tingkatsangat rendah.Hal ini memungkinkan penggunaan sel puncamesenchymal secara alogenik tanpa perlu pencocokan HLAterlebih dahulu.Lebih lanjut, sel punca mesenchymal ini justrumemiliki kemampuan untuk meningkatkan populasi sel Tregulatory, yang bersifat mensupresi imunitas yang berlebih.

Dalam beberapa tahun terakhir telah dilaporkan penggunaan stem selmesenkimal pada pasien dengan GVHD (Graft versusHost Disease) dan pasien autoimunitas.Mekanisme imunosupresi stem sel mesenkimal masih terusdipelajari, namun hingga saat ini diperkirakan bahwa stem selini mampu menghasilkan beberapa mediator antara lainindoleamine 2,3,-dioxygenase dan Galectin-1 yang memiliki efekimunosupresi.

Stem selmesenkimal dalam kondisi yang sesuai dapatmenghasilkan sel tulang rawan (chondrocyte), sel pembangun tulang keras(osteoblast), dan sel lemak (adipocyte).Saat ini stem sel telah dikembangkan sebagai terapi berbagaipenyakit termasuk kelainan hematologi (leukemia, anemia, thalasemia, dan sebagainya), penyakit degeneratif (gangguan pembuluhdarah, infark jantung, penyembuhan luka), terapi kerusakancartilage pada cedera sendi, stem selmesenkimal digunakandalam metode pencegahan terjadinya graft vs host reactionpada transplantasi allogenic, serta pemanfaatan sifat imunosupresipada penderita penyakit autoimun.

 

Gambar dari chondrocyte.

Sumber :http://www.gentaur.com/images/013625fig6-10.gif

Saat ini penelitian sel punca terus berkembang dan begitubanyak penemuan baru yang dilaporkan setiap harinya. Olehkarena itu untuk memperoleh informasi terkini masyarakatkhususnya para dokter perlu terus memantau setiap publikasiilmiah yang dihasilkan dari pengembangan stem sel ini.

MEKANISME KERJA STEM SEL

Yaitu melalui 3 mekanisme :

  1. Menciptakan lingkungan mikro yang kondusif untuk regenerasi sel endogen jaringan,
  2. Transdiferensiasi (sel stem dewasa akan berubah menjadi seljaringan pengganti yang rusak)
  3. Dan melalui fusi sel.

Memang sampai sekarang pertanyaan yang timbul adalah bagaimana tubuh kita dapat memperbaiki jaringan yang rusak? Pada tanaman dan organisme sederhana seperti hydra, planaria, atau salamander dan newt, jika cabang pohon dipotong atau kaki salamander dipotong maka secara otomatis akan tumbuh kembali.

Telah terbukti pada organisme sederhana ini sel stem sangat besar peranannya. Dengan penemuan bahwa sel stem embrionik dan dewasa dapat berkembang biak secara tidak terbatas dan dapat mengalami transdiferensiasi, maka sekarang sudah jelas bahwa perbaikan kerusakan jaringan tubuh dapat diperbaiki oleh sel stem dewasa yang beredar dalam darah dan sel stem yang terdapat dalam setiap organ.

Dengan penemuan ini maka teoritis setiap kerusakan dapat diperbaiki dengan melakukan infus sel stem eksogen karena sel stem endogen tidak cukup banyak untuk dapat melakukan regenerasi. Sumber sel stem endogen yang paling mudah didapatkan adalah sel stem sumsum tulang dan sel stem UCB, jika kita menghendaki sel stem otolog. Karena itu pengambilan dan penyimpanan sel stem UCB akan sangat bermanfaat, tidak hanya untuk pengobatan kanker pasca radiasi atau pemberiankemoterapi dosis tinggi, tetapi juga untuk memperbaiki kerusakan jaringan dan organ tubuh. Sel stem ini dapat dipergunakan untuk melakukan rejuvenasi dan regenerasi jaringan dan organ tubuh yang rusak.

Gambar dari stem sel sumsum tulang.

Sumber :http://stemcells.nih.gov/StaticResources/info/scireport/images/figure43.jpg

Sel stem mesenkimal dapat membentuk chondroblast yang tertanam di matriks dan menjadi chondrocytes, dan stem sel pun dapat membentuk osteoblastdan melalui tissue engineering sel stem dapat diarahkan sedemikian rupa sehingga dapat membentuk jaringan tulang rawan / kartilago, yang dapat dimasukkan ke dalam sendi sehingga dapat berfungsi sebagai pengganti tulang rawan yang rusak. Jika kerusakan tulang rawan masih ringan maka sel stem dapat langsung dimasukkan ke dalam sendi; sel stem akan berubah menjadi chondroblast dan membentuk lapisan tulang rawan baru.

Dua atau lebih chondrocytes akan membentuk lacunae. Selompok chondrocytes disebut cell nests atau isogenous cell groups. Mereka memiliki inti euchromatic dan noda oleh zat warna dasar.

 

Gambar dari kartilago.

Sumber :http://www.ouhsc.edu/histology/Glass%20slides/71_03a.jpg

 

Gambar dari osteoblast.

Sumber :http://www.btec.cmu.edu/tutorial/cells/osteoblast%20cells.jpg

Cara pemberian stem sel yaitu dengan penyuntikan stem sel secara langsung, dimana setelah itu stem sel dibiarkan tumbuh dan beregenerasi menjadi organ yang rusak, dan tidak ada obat untuk menumbuhkan stem sel.

 

Gambar dari tulang.

Sumber :http://stke.sciencemag.org/content/develop/vol135/issue11/images/large/DEV018044F7.jpeg

 

B A B   V I I

P E N U T U P

Sendi lutut merupakan persendian yang paling besar pada tubuh manusia. Sendi ini terletak  pada  kaki  yaitu  antara  tungkai atas dan tungkai bawah. Pada dasarnya sendi lutut ini terdiri dari dua articulatio condylaris diantara condylus femoris medialis dan lateralis dan condylus tibiae yang terkait dan sebuah sendi pelana , diantara patella dan fascies patellaris femoris. Gerakan yang dapat dilakukan oleh sendi lutut yaitu gerakan fleksi , ekstensi dan sedikit rotatio.

Fungsi dari sendi lutut ini adalah untuk mengatur pergerakan dari kaki, dan untuk menggerakkan kaki ini diperlukan koordinasi berikut ini :

  • Otot- otot yang membantu menggerakkan sendi.
  • Capsul sendi yang berfungsi untuk melindungi bagian tulang yang bersendi supaya jangan lepas bila bergerak.
  • Adanya permukaan tulang yang dengan bentuk tertentu yang mengatur luasnya gerakan.
  • Adanya cairan dalam rongga sendi yang berfungsi untuk mengurangi gesekan antara tulang – tulang rawan pada permukaan sendi.
  • Ligamentum - ligamentum yang ada di sekitar sendi lutut yang merupakan penghubung kedua buah tulang yang bersendi sehingga tulang menjadi kuat untuk melakukan gerakan-gerakan tubuh.

Hampir semua sendi dapat dilakukan arthroscopy, namun, sendi - sendi yang paling sering dilakukan arthroscopy adalah pada sendi lutut, bahu dan pergelangan tangan.Arthroscope merupakan instrumen yang sensitif, diameternya kurang dari 5 milimeter, memiliki sebuah sumber cahaya dengan serat fiber, dan terdapat kaca pembesar pada ujungnya.

Instrumen - instrumen arthroscopy mempunyai kemampuan untuk memotong atau mencukur material isi sendi yang dapat dimasukkan melalui portal yang lain pada sendi. Jika diperlukan, sebuah kamera kecil dapat disambungkan pada arthroscope sehingga gambaran sendi dapat dilihat pada layar monitor untuk memudahkan pemeriksaan.

Pada masa kini dan merupakan tantangan bagi para ahli adalah untuk mencegah MRI pada pasien - pasien yang secara pasti membutuhkan arthroscopy terapeutik dan mencegah arthroscopy yang invasif ketika terdapat lesi yang tidak dapat diterapi secara bedah.Keuntungan menggunakan arthroscopy sangatlah banyak, dan berlawanan dengan kerugiannya yang sangat sedikit.

Lutut dapat dibagi menjadi beberapa kompartemen untuk pemeriksaan, yaitu kantung suprapatelar dan sendi patelofemoral; “gutter” medial; kompartemen medial; fisura intercondilaris; kompartemen posteromedial; kompartemen lateral, dan “gutter” lateral.

Sebagian besar, meniscus adalah avascular, yang artinya tidak ada aliran pembuluh darah.Hanya permukaan luar dari meniscus saja yang mendapat sedikit pasokan darah, dan daerah ini disebut zona merah. Bagian meniscus, paling dekat dengan pusat lutut, disebut juga zona putih, yang tidak memiliki aliran pembuluh darah sama sekali. Meskipun tepi luar meniscus ( zona merah ) memiliki peluang bagus penyembuhan, namun kerusakan lebih lanjut sehingga menuju ke bagian pusat meniscus, tidak akan sembuh dengan sendirinya. Kerusakan zona putih meniscus sering membutuhkan pembedahan.

Cedera meniscus, biasanya akan menimbulkan rasa nyeri tajam pada sisi lutut yang mengalami cedera. Nyeri awal dan bengkak akan hilang, akan tetapi akan terus mererus merasakan nyeri tajam ketika berputar mendadak. Lutut mungkin akan terkunci ketika bergerak fleksi atau ekstensi, atau anda mungkin tidak akan mampu bergerak fleksi atau ekstensi secara bebas.

Prosedur pembedahan cedera meniscus dapat menggunakan berbagai macam cara, yaitu partial menisectomi, jahitan perbaikan, jahitan anchor, biostringer insertion technique with bio – absorbable device, fast – fix meniscal repair system, dan transplantasi meniscal.

Secara alamiah mahluk hidup telah dibekali dengan berbagai macam kemampuan untuk mempertahankan diri. Hal ini termasuk pula kemampuan dalam meregenerasikan bagian tubuh yang secara terus-menerus perlu diperbaharui, Tugas pembaharuan sel - sel ini diemban oleh stem sel; oleh karena itu stem sel memiliki peran vital dalam perkembangan, pertumbuhan, kelangsungan, dan perbaikan semua jaringan yang hidup termasuk otak, tulang, otot, saraf, darah, kulit, dan organ lainnya.

Stem sel tergantung pada sumsum tulang, darah tepi, darah tali pusat, lipoaspirat, darah menstruasi, pulpa gigi, jaringan tulang rawan (cartilage), jaringan tulang keras (osseous), parenkim hepar, dan jaringan ventrikel jantung. Berdasarkan tipe sel yang dihasilkan, stem sel dapat dikelompokanmenjadi stem sel hematopoetik dan stem sel mesenkimal.

Stem sel bekerja melalui 3 mekanisme :

  1. Menciptakan lingkungan mikro yang kondusif untuk regenerasi sel endogen jaringan,
  2. Transdiferensiasi (sel stem dewasa akan berubah menjadi sel jaringan pengganti yang rusak)
  3. Dan melalui fusi sel.

Sel stem mesenkimal dapat membentuk chondroblast yang tertanam di matriks dan menjadi chondrocytes, dan stem sel pun dapat membentuk osteoblastdan melalui tissue engineering sel stem dapat diarahkan sedemikian rupa sehingga dapat membentuk jaringan tulang rawan / kartilago, yang dapat dimasukkan ke dalam sendi sehingga dapat berfungsi sebagai pengganti tulang rawan yang rusak. Jika kerusakan tulang rawan masih ringan maka sel stem dapat langsung dimasukkan ke dalam sendi; sel stem akan berubah menjadi chondroblast dan membentuk lapisan tulang rawan baru.

Dua atau lebih chondrocytes akan membentuk lacunae. Selompok chondrocytes disebut cell nests atau isogenous cell groups. Mereka memiliki inti euchromatic dan noda oleh zat warna dasar.

D A F T A R   P U S T A K A

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