APLIKASI TERAPI STEM CELL

AG. Soemantri
BAGIAN ILMU KESEHATAN ANAK FAKULTAS KEDOKTERAN UNDIP / RSUP DR KARIADI SEMARANG

PENDAHULUAN (1)
UU RI No. 36 tahun 2009 tentang kesehatan, yang menyangkut masalah transplantasi Pasal 64 ayat 1, ayat 2, ayat 3 Pasal 65 ayat 1, ayat 2, ayat 3 Pasal 66 Pasal 70 ayat 1, ayat 2, ayat 3

PENDAHULUAN (2)
“Frischzellenthherapeutica” (i.e. cell xenotransplants) are outside of regulatory controls of the State because they are neither drugs nor (therapeutica”, (“arzneimittel” in German), but are another form of medication, individually prepared by a physician, for his specific patient, by agreement with his patient, confirmed by the signed informed consent prescribed by law (February, 16, 2000) 2. They are prepared for one time use only
1.

PENDAHULUAN (3)
3. They have no “shelf-life” 4. They are not distributed through the

usual channels, i.e. through pharmacies 5. They have to be implanted on a date set prior to the start of their preparation 6. Their implantation has to be carried out by the same physician who wrote a prescription for the stem cell xenotransplants for the named patient.

PENDAHULUAN (4) BUNDESVERFASSUNGSGERICHT Der Bund ist nach Art. 19 GG nicht befugt. 74 Abs. 1 Nr. 16. 2009) . 2000) The International Xenotransplantation Association Consensus Statement on Conditions for Undertaking Clinical Trials of Porcine Islet Products in Type 1 Diabetes (July. 27. die der Arzt zur Anendung bei eigenen Patienten herstellt (February. die Herstellung solcher Arzneimittel zu regeln.

DEFINISI STEM CELL (SEL PUNCA) Stem Cell adalah sel yang mampu memperbanyak diri dalam waktu yang lama dan dapat berkembang menjadi berbagai sel khusus / spesifik yang membentuk jaringan. Potency kemampuan berdeferensiasi kearah sel tertentu Self-renewal kemampuan memperbanyak melalui siklus dari pembelahan sel sambil mempertahankan kondisi undifferentiated .

. Kemampuan untuk berproliferasi menjadi sel yang identik dengan sel asalnya 3.KRITERIA STEM CELL ( SEL PUNCA ) Belum mempunyai fungsi 2. Berubah menjadi sel tipe lain dengan fungsi yang spesifik 1.

Cell Cycle Control.Repopulating Patterns of Primitive Hemato poietic Stem Cell .Differentiated parental DNA Chain causes stem cell pattern of cell-type switching in Schizosaccharomyces pombe . Cheekpoints.Stem Cell Biology .On equivalence groups and the Notch/LIN-12 .Senescence of Dividing Somatic Cells .1. GENERAL ISSUES . and Stem Cell Biology .

The Drosophila Ovary : An in vivo stem cell system .Primordial Germ cells as stem cell . EARLY DEVELOPMENT .Trophoblast stem cells .Embryonic stem cells .Embryonal Carcinoma cells as embryonic stem cells .2.Male Germ-line stem cell .

The hemangioblast .Hematopoietic stem cell : Lymphopoiesis and the problem of commitment versus plasticity .Hematopoietic stem cell : molecular diversification and developmental irrelationships .Mesenchymal stem cells of human adult bone marrow .3.Fate mapping of stem cell . MESODERM .

Pancreatic stem cell . ENDODERM . ECTODERM .Stem cell and neurogenesis .Epidermal stem cell 5.Liver stem cell .4.Stem cells in the Epithelium of the small intestine and colon .

BASIC CONCEPT OF CELLULAR AND MOLECULAR BIOLOGY .

2 October 2003 .DOGMA CENTRAL DNA RNA Protein Mathematical Biosciences Institute (Ohio State Univ).

etc.) .3 MOLECULES OF LIFE All life depends on three critical molecules: DNAs – Hold information on how cell works RNAs – Act to transfer short pieces of information to different parts of cell – Provide templates to synthesize into protein Proteins – Form enzymes that send signals to other cells and regulate gene activity – Form body’s major components (e.g. hair. skin.

ANOTHER VIEW OF CENTRAL DOGMA A gene is expressed in 3 steps: 1) Transcription: RNA synthesis 2) Splicing: removal of intron sequence from RNA 3) Translation: Protein synthesis .

us/science/ps/sci/ibbio/chem/nucleic . • The sequence of nucleotides on DNA template determines the sequence on RNA by following the rule of base-pair complementarity.e. RNA polymerase II. G – C. A – U. • Transcription continues until entire gene is copied to RNA.or..A. i. C – G. T.TRANSCRIPTION • Transcription is initiated by a complex of transcription factors binding to the promoter site located upstream of the gene •An enzyme.gresham.k12. travels along the gradually unzipped DNA template and polymerizes nucleotides into an RNA. Animation Source of diagram: http://ghs.

SPLICING pre mRNA Exon 1 Intron 1 Exon 2 Intron 2 Exon 3 mature mRNA .

UAG. and ends with any of UAA. • Genetic code: three base pairs of RNA (called a codon) determine one amino acid based on a fixed table. • Translation always starts at AUG (start codon). the nucleotide sequence on mRNA determines the amino acid sequence by genetic code. or UGA (stop codon) .TRANSLATION (1) • By translation.

wiley. the tRNA with the anticodon CGG corresponds with the codon GCC and attaches alanine amino acid onto the peptide chain. Most of the tRNAs function as carriers of amino acids and participate in protein synthesis. For example. Ribosome: a complex of protein and rRNA Animation Source of diagram: http://www.com/legacy/college/boyer/0470003790/structure/tRNA/ .TRANSLATION (2) Transfer RNAs (tRNAs): small RNA molecules.

in 2010 Individualized Ther. Diabetes Alzheimers Parkinson .MODERN TECHNOLOGY IN MEDICINE Modern technology: Diagnostic Early Screening Prognostic Follow up Human genome: Gene ther. Stem cell Antisense Biomedical Engineering New approaches: Genome Analysis: Expression gene analysis Micro Array Protein analysis New hopes: Cancer Vascular/Heart dis.

000 cells that is 100 billion km of DNA .HOW MUCH DNA DO WE HAVE? humans have 2 x 23 chromosomes EACH cells contains 6 billion bases DNA that is 1 meter of DNA a human being has >100.000.000.000.

CELL – CELL COMMUNICATION Receptors Signal transductions Second messengers molecules Nuclear transcription factors Gene activations Protein  Respons .

CELLS CAN WITHDRAW FROM THE CELL CYCLE AND DISMANTLE THE REGULATORY MACHINERY G0 is a quiescent state Cdks and cyclins disappear Some cells enter G0 temporarily and divide infrequenty (I.e. hepatocytes) Other differentiated cell types (neurons) spend their life in G0 .

and consists of: – Mitosis (division of nucleus) – Cytokinesis (division of cytoplasm) Cells Apoptosis (cell death) decreases the number of cells.Cell division increases the number of somatic (body) cells. . Both cell division and apoptosis occur during normal development and growth.

“Start” checkpoint •Controls G1/S transition •Commits cell to another round of cell division G2/M checkpoint •Checks that DNA is fully replicated M checkpoint •Is DNA division (chromosome segregation) progressing correctly? .

diploid) . 6 x 109 bp • ~1.8 meters total length • total length reduced via associates with proteins • individual DNA molecules condensed into chromosomes • humans have 22 pairs + X/X or X/Y (ie.CHROMOSOMES • genomic DNA is very long • humans.

upstream exon intron exon downstream Initiation codon termination codon 5’ 3’ 5’ 3’ .

bioinfbook.org/ .CENTRAL DOGMA OF MOLECULAR BIOLOGY DNA Sequence (splited by genes) RNA Amino Acid sequence protein phenotype Adapted from http://www.

CENTRAL DOGMA Gene Transcription Genome RNA Transcriptome Translation Protein Proteome .

.

enzym repair – dll RNA RNA RNA RNA RNA RNA .REGULATORS : PROLIFERATION. p53. APOPTOSIS. DIFFERENTIATION.CDKI – GF : GM-CSF. caspase – Gadd. REPAIR Genome : Genes : – Cell cycle – Differentiati o – Apoptosis – Repair – Metabolism – etc Transcriptome Proteome Protein: – cyclin. FGF – Bcl-2. CDK.

HOW TO UNDERSTOOD ?? GENE: Cytogenetics FISH DNA analysis Southern blot +/PCR – specific MLPA Sequencing : SSCP Gene activ: RNA Northern blot RT.PCR RNA-se protection Assay Micro array R-ISH Gene active : Protein Western Blot SDS-PAGE ELISA FISH .

APLIKASI STEM CELL (SEL PUNCA) Tidak semua dibicarakan satu persatu tentang aplikasi Yang disinggung yang pernah dijalankan oleh RSUP Dr Kariadi / FK UNDIP .

BERDASAR ASAL SEL YANG DIPAKAI • Autotransplantasi Dari satu bagian tubuh ke bagian tubuh yang lain pada individu yang sama • Allotransplantasi Antar individu pada spesies yang sama • Xenotransplantasi Antar spesies yang berbeda .

Metoda Autolog .Metoda Allolog . yang digunakan untuk cangkok sumsum tulang .MESODERM Sel yang berasal dari Mesoderm ini yaitu Mesenchymal Stem Cells of Human Adult Bone Marrow.

2 kasus dengan autolog untuk penderita dengan diagnosis AML M(2) Salah satu sudah lulus Sarjana Kedokteran dan Ekonomi Satu kasus dengan metoda allolo untuk penderita β thallasemia homo zygote . Kariadi tahun 1987.Cangkok Sumsum Tulang telah dilaksanakan di RSUP Dr.

ENDODERM Cangkok hati dilaksanakan di RSUP Dr Kariadi pada tanggal 1 Oktober 2006 dengan atresia billier. anak “A” laki-laki umur 7 tahun dengan donor sukarela. . Cangkok hati II dilaksanakan di RSUP Dr Kariadi pada Juni 2009 dengan Allagile Syndrome. anak “U” laki-laki umur 15 bulan dengan donor dari ibu kandungnya.

European Community Council directive 2001/83/EC. UU seluruh negara Uni eropa Jaminan keamanan (+) Hewan yang dipakai (kelinci) memenuhi persyaratan yang dikeluarkan oleh : Guidelines on Infectious Disease Issues in Xenotransplantasi Merupakan hewan dari galur tertutup yang diisolasi dan diawasi dari kemungkinan tertular penyakit (diawasi 7 turunan ) .XENOTRANSPLANTASI  AMANKAH ?? Legalitas (+) Keputusan MA German No 1 BvR420/97.

indeks volume otak. perkembangan motorik Evaluasi mental dan psikologis 83 penderita SD yang diterapi : terjadi penurunan hiperaktivitas.EVIDENBASED HASIL PENELITIAN TERAPI CANGKOK STEM CELL 3000 penderita SD yang diterapi  25% bisa sekolah secara normal Outcome terapi : terjadi peningkatan TB. LK. perkembangan mental. peningkatan konsentrasi dan peningkatan kemampuan bahasa ekspresif Evaluasi imunologis : terjadi peningkatan IgA dan penurunan IgG  Menurunnya frekuensi dan beratnya infeksi bakteri . IQ.

EVIDENCE BASED Pada Cangkok Stem Cell (CST) usia ≤ 3½ tahun kenaikan MDI > 50 point terjadi pada :  17 % bila tidak di CST  58 % pada CST I  71 % pada CST II Pada usia 4-9 tahun kenaikan 25-49 point .

Phosphorylation targets of DYRK1A. which have been implicated in a number of biological processes and DSassociated phenotypes. . including endocytosis and AD.Figure 2. The Hsa21-encoded kinase DYRK1A has been shown to phosphorylate a multitude of targets.

siklus sel Definisi dan jenis-jenis. cangkok hati. cangkok stem cell . kriteria stem cell (sel punca) Dasar hukum Dasar keberhasilan asosiasi stem cell Aplikasi yang pernah dilakukan di RSUP Dr Kariadi/FK UNDIP : cangkok sumsum tulang.RINGKASAN Telah diutarakan konsep dasar biomolekuler.

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