vi

DAFTAR ISI

HALAMAN JUDUL ........................................................................................ i

HALAMAN PENGESAHAN .......................................................................... ii

SURAT PERNYATAAN................................................................................. iii

PRAKATA .................................................................................................... iv

DAFTAR ISI .................................................................................................... vi

DAFTAR SINGKATAN ................................................................................. ix

DAFTAR GAMBAR ....................................................................................... xi

DAFTAR TABEL ............................................................................................ xiii

DAFTAR LAMPIRAN .................................................................................... xiiii

INTISARI .................................................................................................... xivi

BAB I PENDAHULUAN................................................................................ 1

1.1. Latar Belakang .............................................................................. 1

1.2. Rumusan Masalah ......................................................................... 3

1.3. Tujuan Penelitian........................................................................... 3

1.3.1 Tujuan Umum ..................................................................... 3

1.3.2 Tujuan Khusus .................................................................... 3

1.4. Manfaat Penelitian......................................................................... 4

1.4.1 Manfaat Teoritis .................................................................. 4

1.4.2 Manfaat Praktis ................................................................... 4

BAB II TINJAUAN PUSTAKA ...................................................................... 5

2.1. Proliferasi Hematopoietic Stem Cell ............................................. 5

vii

2.2. Siklus Sel ....................................................................................... 8

2.2.1 Fase ..................................................................................... 8

2.2.1 Interaksi Antara Protein Yang Terlibat Dalam Siklus Sel . 12

2.3. Hematopoietic Stem Cell ............................................................... 15

2.3.1 Sumber Hematopoietic Stem Cell ....................................... 15

2.3.1 Peripheral Blood Hematopoietic Stem Cell ........................ 16

2.4. Faktor-Faktor yang Mempengaruhi Proliferasi Stem Cell ............ 18

2.5. Usia ................................................................................................ 19

2.4.1 Definisi ................................................................................ 19

2.4.2 Konsep Bertambah Usia (Menua) ....................................... 20

2.4.3 Senescence ........................................................................... 21

2.6. Hubungan antara Usia terhadap Proliferasi Hematopoietic

Stem Cell ....................................................................................... 22

2.7. Kerangka Teori .............................................................................. 24

2.8. Kerangka Konsep .......................................................................... 24

2.9. Hipotesis ........................................................................................ 24

BAB III METODE PENELITIAN................................................................... 25

3.1 Jenis dan Rancangan Penelitian .................................................... 25

3.2 Variabel dan Definisi Operasional ................................................ 25

3.2.1. Variabel ............................................................................. 25

3.2.2. Definisi Operasional .......................................................... 25

3.2.2.1. Usia...................................................................... 25

viii

3.2.2.2. Proliferasi ............................................................ 26

3.3 Subyek dan Sampel Penelitian ...................................................... 26

3.3.1. Subyek Penelitian .............................................................. 26

3.3.2. Sampel Penelitian .............................................................. 27

3.4 Alat dan Bahan Penelitian ............................................................. 28

3.4.1. Alat Penelitian ................................................................... 28

3.4.1.1. Alat Kultur........................................................... 28

3.4.1.2. Alat Kultur Hematopoietic Stem Cell.................. 28

3.4.1.3. Incubation and Working Culture Area ................ 28

3.4.1.4. Alat Lain .............................................................. 28

3.4.2. Bahan Penelitian ................................................................ 29

3.5 Prosedur Penelitian ........................................................................ 29

3.5.1 Perolehan Ethical Clearance ............................................. 29

3.5.2 Pengambilan Sample Darah .............................................. 29

3.5.3 Teknik Isolasi Hematopoietic Stem Cell ........................... 30

3.5.4 Kultur sel ........................................................................... 31

3.5.5 Pemanenan Sel .................................................................. 31

3.5.6 Penghitungan hematopoietic stem cell .............................. 31

3.5.7 Proses Pemanenan Sel ....................................................... 32

3.5.8 Penghitungan Proliferasi Hematopoietic Stem Cell .......... 32

3.6 Tempat dan Waktu Penelitian ....................................................... 33

3.6.1 Tempat Penelitian .............................................................. 33

3.6.2 Waktu Penelitian ............................................................... 33

ix

3.7 Analisis Data ................................................................................. 33

3.8 Alur Penelitian............................................................................... 34

BAB IV HASIL PENELITIAN DAN PEMBAHASAN ................................. 35

4.1 Hasil Penelitian ............................................................................. 35

4.2 Pembahasan Penelitian .................................................................. 38

BAB V KESIMPULAN DAN SARAN ........................................................... 41

4.1 Kesimpulan.................................................................................... 41

4.2 Saran .............................................................................................. 41

DAFTAR PUSTAKA ...................................................................................... 42

LAMPIRAN .................................................................................................... 46

x

DAFTAR SINGKATAN

CDK : Cyclin-Dependent Kinase

DDR : DNA damage response

DNA : Deoxyribonucleic Acid

DSB : Double-strand breaks ()

E2F : E2 Factor

G1 : Gap 1

G2 : Gap 2

mRNA : Messenger Ribonucleic acid

NIH : National Institutes of Health

p53 : Tumor Protein p53

Rb : Retinoblastoma

S : Synthesis

xi

DAFTAR GAMBAR

Gambar 2.1 Model pembelahan Stem Cell. ........................................................... 7

Gambar 2.2 Skema siklus Sel. ............................................................................... 9

Gambar 2.3 Nasib Stem Cell yang mengalami kerusakan DNA. .......................... 9

Gambar 3.1 Alur penelitian. ................................................................................ 34

Gambar 4.1 Morfologi Hematopoietic Stem Cell ............................................... 35

Gambar 4.2 Grafik rerata jumlah proliferasi Hematopoietic Stem Cell pada pasien

usia 20 tahun dan 50 tahun .............................................................. 36

xii

DAFTAR TABEL

Tabel 4.1 Hasil Uji Normalitas Kelompok ......................................................... 37

Tabel 4.2 Hasil Uji Homogenitas Kelompok ..................................................... 37

Tabel 4.3 Hasil Uji Independent Sample T-Test................................................. 37

xiii

DAFTAR LAMPIRAN

Lampiran 1 Hasil Uji Deskriptif Data Hasil Uji Deskriptif Jumlah Proliferasi

Hematopoietic Stem Cell ................................................................. 46

Lampiran 2 Hasil Uji Normalitas dan Homogenitas Jumlah Proliferasi

Hematopoietic Stem Cell ................................................................. 47

Lampiran 3 Hasil Uji Perbedaan Antar Kelompok Dengan Independent

Sample T-Test .................................................................................. 48

Lampiran 4 Dokumentasi Penelitian ................................................................... 49

Lampiran 5 Ethical Clearance ............................................................................ 50

Lampiran 6 Surat Keterangan Penelitian ............................................................. 51