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"kegagalan hati. Organoid hati dapat digunakan sebagai bahan untuk BAL. Organoid hati merupakan rekonstruksi hati kultur 3D dari sel punca dan sel-sel lainnya yang menyerupai mikrostruktur hati in vivo dan memiliki fungsi hati. Organoid hati juga dapat digunakan untuk uji obat dan sebagai model unutk mempelajari penyakit hati.Metode : Organoid hati pada penelitian ini direkonstruksi dari hepatosit, sel stelata hepatika (LX2), sel punca mesenkimal asal tali pusat (UC-MSCs), dan sel punca hematopoiesis asal darah tali pusat (UCB-CD34+). Hepatosit primer tikus, LX2, UC-MSCs dan UCB-CD34+ diko-kultur dalam 11 formulasi rasio selama 2 hari. Formulasi rasio yang membentuk sferoid dikultur dalam 4 medium kultur selama 5 hari, dipanen dan dilakukan analisa viabilitas. Rasio dengan viabilitas tertinggi merupakan rasio optimal dalam medium kultur optimal untuk rekonstruksi organoid hati. Rasio hepatosit : LX2 : UC-MSCs : UCB-CD34+ optimal 5 : 1 : 2 : 2 diko-kultur dalam medium kultur optimal Williams E yang disuplementasi dengan PRP, ITS dan dexamethasone selama 14 hari dan dilakukan analisa morfologi, fungsi hati dan potensi angiogenesis.Hasil : Viabilitas organoid bertahan hingga hari ke-14 dan ekspresi protein albumin, ekspresi protein GOT dan ekspresi protein CD31 cukup stabil hingga hari ke-14. Ekspresi gen Albumin meningkat hingga hari ke-14 sedangkan ekspresi gen GOT menurun hingga hari ke-14. Sekresi urea menurun hingga hari ke-5 dan sekresi albumin menurun hingga hari ke-7.Kesimpulan : Organoid hati ini direkonstruksi dari hepatosit primer, LX2, UC-MSCs, UCB-CD34+ dengan rasio optimal 5 : 1 : 2 : 2 dalam medium kultur optimal sederhana dan ekonomis Williams E yang disuplementasi PRP, ITS dan dexamethasone. Organoid hati ini dapat mempertahankan viabilitas dan fungsi hingga hari ke-14. Organoid hati penelitian ini dapat digunakan sebagai model untuk uji obat dan dapat dikembangkan untuk menjadi bahan BAL.......Introduction : Bioartificial Liver (BAL) is being developed to be an alternative therapy for liver failure. Liver organoids can be used as prototype material for BAL. Liver organoids are 3D cultured liver reconstructions of stem cells and other cells that resemble the liver microstructure in vivo and perform liver function. Liver organoids also can be used for drug testing and as a model for liver disease pathogenesis.Methods : Liver organoids in this study were reconstructed from hepatocytes, hepatic stellate cells (LX2), human umbilical cord-mesenchymal stem cells (UC-MSCs), and human umbilical cord blood (UCB) hematopoiesis stem cells CD34+. Rat primary hepatocytes, LX2, UC-MSCs and UCB-CD34+ were co-cultured in 11 ratio formulations for two days. The ratio formed spheroid were cultured in four culture medium for five days, harvested and analyzed for viability. The ratio with the highest viability was the optimal ratio in the optimal culture medium for hepatic organoid reconstruction. The optimal ratio 5 : 1: 2 : 2 of Hepatocytes : LX2 : UC-MSCs : UCB-CD34+ was co-cultured in optimal culture medium Williams E supplemented with PRP, ITS and dexamethasone for 14 days and analyzed for morphology, liver function and angiogenesis potential.Results : Liver organoids viability maintained until day 14 and albumin protein expression, GOT protein expression and CD31 protein expression were quite stable until day 14. Albumin gene expression increased until day 14, while GOT gene expression decreased until day 14. Urea secretion decreased until day 5 and albumin secretion decreased until day 7. Conclusion : These liver organoids were reconstructed from optimal ratio 5 : 1 : 2 : 2 of primary hepatocytes, LX2, UC-MSCs, UCB-CD34+ in simple and economical optimal culture medium Williams E supplemented by PRP, ITS and dexamethasone. These liver organoids maintained viability and liver function until day 14. These liver organoids can be used as a model for drug testing and can be developed to become a BAL material for future application."

"Excessive hepatocyte apoptosis induced by bile acid accumulation occurred in severe obstructive jaundice, and impair the liver secretion function. The objective of this study is to determine whether the inhibition of bile acid accumulation through bile duct decompression affect the excessive hepatocyte apoptosis and caused improvement the liver secretion functions on human model. In this study we use a before and after study on severe obstructive jaundice patients due to extra hepatic bile duct tumor was decompressed. Bile duct decompression was performed as a model of the role ofinhibition of bile acid accumulation inhibition bile acid accumulation and excessive hepatocyte apoptosis. Bile acid and marker of liver secretion functions were serially measured. Liver biopsy pre and post decompression was performed for Hepatocyte apoptosis pathologic examination by TUNEL fluorescing, which measured by 2 people in double blinded system. Total bile acid, and liver secretion functions were measured by automated chemistry analyzer. The result ofthis study shows that twenty one severe obstructive jaundice patients were included. After decompression the hepatocyte apoptosis index decreased from an average of 53.1 (SD 105) to 11.7 (SD 13.6) (p < 0.05). Average of bile acid serum decreased from 96.4 (SD 53.8) to 19.9 (SD 39.5) until 13.0 (SD 12.6) μmol/L (p < 0.05) Total bilirubin decreased from 20.0 (SD 8.9) to 13.3 (SD 5.0) until 6.2 (SD 4.0) mg/dL (p < 0.05), while the phosphates alkaline (ALP) and γ-glutamil transpeptidase (γ-GT) activities also decreased significantly. In conclusion, bile acids accumulation and excessive hepatocyte apoptosis through bile duct decompression improve the liver secretion functions by inhibition mechanism."

"Latar Belakang: Fibrosis hati disebabkan cedera hati kronis akan menjadi sirosis. Vesikel ekstraseluler (VE) dan Hepatocyte Growth Factor (HGF) banyak dipelajari sebagai terapi fibrosis dan regenerasi hati. Penelitian ini memanfaatkan kombinasi VE dan recombinant human-HGF ( rh-HGF) sebagai terapi alternatif fibrosis hati pada model tikus ligasi duktus bilier (LDB).Metode: Sebelas tikus Sprague Dawley (SD) menjalani LDB, 5 tikus kontrol dan 6 tikus mendapat perlakuan injeksi VE 150 uL dan rh-HGF 0,1 mg intravena sejak 3 minggu pasca LDB, selama 7 hari. Satu tikus kontrol diterminasi 3 minggu pasca LDB sebagai data dasar. Tikus-tikus kelompok kontrol dan perlakuan diterminasi pada 1 hari dan 2 minggu setelah injeksi terakhir. Dilakukan penilaian skor Laennec hati serta kadar HGF, alanine aminotransferase (ALT) dan aspartate aminotransferase (AST).Hasil: Histopatologi 3 minggu pasca LDB menunjukkan skor Laennec 2. Skor fibrosis kelompok kontrol (KK) dan kelompok perlakuan (KP) 1 minggu dan 2 minggu pasca injeksi VE dan rh-HGF seluruhnya dengan skor 2. Kadar HGF pada KP lebih rendah secara signifikan dibandingkan dengan KK 1 hari pasca injeksi terakhir (1,35+0,06 vs 1,53+0,06; p<0,001), semakin menurun setelah 2 minggu pasca injeksi terakhir namun tidak bermakna secara statistik 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). Kadar AST 1 hari pasca injeksi terakhir; KK 1,66+0,05 KP 0,91+0,12 debgan p = 0,001. Setelah 2 minggu pasca injeksi; kadar AST pada kedua kelompok menurun 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021). Kadar ALT pada kelompok perlakuan lebih rendah secara signifikan pada 1 hari pasca injeksi dan 2 minggu pasca injeksi dengan nilai p<0,001 dan 0,033a......Background: Fibrosis of the liver due to a chronic liver injury will become cirrhosis at the end-stage. The Extracellular Vesicles (EV) and hepatocyte growth factor (HGF) are recently learned as much as fibrosis and liver regeneration therapy. This study aims to know the result of using a combination of EV and recombinant human HGF (rh-HGF) as an alternative therapy due to liver fibrosis on the rat bile duct ligation (BDL) model.Methods: Eleven BDL Sprague Dawley (SD) were divided into two groups, five mice as the untreated control group and six mice as the treatment group was getting an EV 150 ul and rh-hgf 0.1 mg intravenous injection three weeks after BDL, for seven days. One control rat is expanded three weeks after BDL as baseline data. The control and treatment group mice were projected at day one and two weeks after the final injection. This study was assessed from liver fibrosis by using Laennec score, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Hepatocyte Growth Factor (HGF) level.Results: Scoring of histopathology by using the Laennec score at 3 weeks after BDL was 2.Meanwhile scoring of fibrosis of the control group and treatment group at 1 week and 2weeks after ve and rh-hgf injection were 2. HGF level of the treatment group was lower significantly than control group at day 1 after last injection (1,35+0,06 vs 1,53+0,06; p<0,001), and within 2 weeks, the number of HGF levels decreased but statistically insignificant; 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). AST level at day 1 after last injection; control group vs treatment group ;1,66+0,05 vs 0,91+0,12, p value = 0,001. 2 weeks after injection; AST level for both group were become lower 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021), and ALT level on treatment group was significantly lower at day 1 and 2 weeks after injection with p value <0,001 and 0, 033a"

"ABSTRAKLatar Belakang : Hepatocyte Progenitor Cell(HPC) merupakan stem cell dari hati yang akan muncul bila terjadi kerusakan hati yang kronis hingga sirosis hati seperti pada penderita hepatitis B kronik. Aktifnya HPC sebagai usaha untuk meregenerasi sel hati akan diikuti oleh migrasi dari Haematopoietic Stem Cell(HSC) ke sel hati dengan tujuan membantu proses regenerasi sel hatiTujuan : Penelitian ini bertujuan mengetahui adakah korelasi antara HPC dan HSC pada derajat Metavir baik nekroinflamasi ataupun fibrosis sebagai dasar untuk melakukan terapi stem cell pada penderita hepatitis B kronik dengan menggunakan HPC dan HSC.Metode : Penderita hepatitis B kronik yang sudah memenuhi kriteria inklusi dan sudah menjalani biopsi hati diperiksa parafin bloknya kemudian dibagi berdasarkan derajat metavirnya yaitu ringan-sedang dan berat. Kemudian dilakukan pewarnaan immunohistokimia untuk HPC dengan CK-19 dan HSC dengan CD34+. setelah itu dihitung jumlah HPC dan HSC dan kemudian dianalisis datanya.Hasil : Didapatkan 17 penderita dengan fibrosis ringan-sedang dan 13 dengan fibrosis berat, serta 21 dengan nekroinflamasi ringan-sedang dan 9 dengan nekroinflamasi berat. Pada fibrosis ringan-sedang dan berat didapatkan perbedaan kadar HPC yang signifikan dgn p=0.003 dan perbedaan kadar HSC yang signifikan dengan p=0.001. Pada nekroinflamasi ringan-sedang dan berat didapatkan perbedaan kadar HPC yang signifikan dengan p=0.014 dan perbedaan kadar HSC yang signifikan dengan p=0.012. Hanya korelasi antara HPC dan HSC pada fibrosis ringan-sedang yang signifikan dengan p=0.003Kesimpulan : Rerata HPC dan HSC pada nekroinflamasi berat lebih tinggi dibandingkan pada nekroinflamasi ringan-sedang. Rerata HPC dan HSC pada fibrosis berat lebih tinggi dibandingkan pada fibrosis ringan-sedang Tidak didapatkan korelasi antara HPC dan HSC pada nekroinflamasi ringan- sedang dan berat. Terdapat korelasi antara HPC dengan HSC pada derajat fibrosis ringan-sedang. Tidak didapatkan korelasi antara HPC dan HSC pada derajat fibrosis berat.

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ABSTRACTBackground :Hepatocyte progenitor Cell (HPC) is a stem cell from the liver that will arise in the event of chronic liver damage such as chronic hepatitis B to cirrhosis of the liver. HPC as an active attempt to regenerate liver cells followed by migration of Haematopoietic Stem Cell (HSC) to liver cells with the goal of helping the regeneration of liver cells.Aims :This study aims to determine the correlation between HPC and HSC as the basis for the conduct of stem cell therapy in patients with chronic hepatitis B by using the HPC and HSC.Methods:Patients with chronic hepatitis B who meet the inclusion criteria which had undergone liver biopsies examined paraffin blocks which divided by degrees of metavir as mild and severe. Then performed immunohistochemical staining for HPC with CK-19 and HSC with CD34+ .After the calculated amount of HPC and HSC and then analyzed the data.Results:There were 17 patients with mild-moderate fibrosis and 13 with severe fibrosis, and 21 with mild-moderate nekroinflamasi and 9 with severe nekroinflamasi. In mild- moderate and severe fibrosis obtained mean significant HPC with p = 0.003 and mean significant HSC with p = 0.001. In nekroinflamasi obtained mean mild- moderate and severe HPC significant with p = 0.014 and the mean HSC significant with p = 0.012. There is a statistically significant correlation between HPC and HSC on mild-moderate fibrosis with p = 0.003.Conclusions:Average of HPC and HSC in severe nekroinflamasi is higher than in mild - moderate nekroinflamasi . Average of HPC and HSC in severe fibrosis is higher than in mild - moderate fibrosis There were no correlation between HPC and HSC on nekroinflamasi mild- moderate and severe . There is a correlation between HSC and HPC in the mild - moderate fibrosis . There were no correlation between HPC and HSC on the degree of severe fibrosis."

"Latar Belakang: Fibrosis hati disebabkan cedera hati kronis akan menjadi sirosis. Vesikel ekstraseluler (VE) dan Hepatocyte Growth Factor (HGF) banyak dipelajari sebagai terapi fibrosis dan regenerasi hati. Penelitian ini memanfaatkan kombinasi VE dan recombinant human-HGF ( rh-HGF) sebagai terapi alternatif fibrosis hati pada model tikus ligasi duktus bilier (LDB).Metode: Sebelas tikus Sprague Dawley (SD) menjalani LDB, 5 tikus kontrol dan 6 tikus mendapat perlakuan injeksi VE 150 uL dan rh-HGF 0,1 mg intravena sejak 3 minggu pasca LDB, selama 7 hari. Satu tikus kontrol diterminasi 3 minggu pasca LDB sebagai data dasar. Tikus-tikus kelompok kontrol dan perlakuan diterminasi pada 1 hari dan 2 minggu setelah injeksi terakhir. Dilakukan penilaian skor Laennec hati serta kadar HGF, alanine aminotransferase (ALT) dan aspartate aminotransferase (AST).Hasil: Histopatologi 3 minggu pasca LDB menunjukkan skor Laennec 2. Skor fibrosis kelompok kontrol (KK) dan kelompok perlakuan (KP) 1 minggu dan 2 minggu pasca injeksi VE dan rh-HGF seluruhnya dengan skor 2. Kadar HGF pada KP lebih rendah secara signifikan dibandingkan dengan KK 1 hari pasca injeksi terakhir (1,35+0,06 vs 1,53+0,06; p<0,001), semakin menurun setelah 2 minggu pasca injeksi terakhir namun tidak bermakna secara statistik 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). Kadar AST 1 hari pasca injeksi terakhir; KK 1,66+0,05 KP 0,91+0,12 debgan p = 0,001. Setelah 2 minggu pasca injeksi; kadar AST pada kedua kelompok menurun 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021). Kadar ALT pada kelompok perlakuan lebih rendah secara signifikan pada 1 hari pasca injeksi dan 2 minggu pasca injeksi dengan nilai p<0,001 dan 0,033a......Background: Fibrosis of the liver due to a chronic liver injury will become cirrhosis at the end-stage. The Extracellular Vesicles (EV) and hepatocyte growth factor (HGF) are recently learned as much as fibrosis and liver regeneration therapy. This study aims to know the result of using a combination of EV and recombinant human HGF (rh-HGF) as an alternative therapy due to liver fibrosis on the rat bile duct ligation (BDL) model.Methods: Eleven BDL Sprague Dawley (SD) were divided into two groups, five mice as the untreated control group and six mice as the treatment group was getting an EV 150 ul and rh-hgf 0.1 mg intravenous injection three weeks after BDL, for seven days. One control rat is expanded three weeks after BDL as baseline data. The control and treatment group mice were projected at day one and two weeks after the final injection. This study was assessed from liver fibrosis by using Laennec score, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and Hepatocyte Growth Factor (HGF) level. Results: Scoring of histopathology by using the Laennec score at 3 weeks after BDL was 2. Meanwhile scoring of fibrosis of the control group and treatment group at 1 week and 2 weeks after ve and rh-hgf injection were 2. HGF level of the treatment group was lower significantly than control group at day 1 after last injection (1,35+0,06 vs 1,53+0,06; p<0,001), and within 2 weeks, the number of HGF levels decreased but statistically insignificant; 0,83 (0,73-0,84) vs 0,76 (0,73-0,80) p=0,248). AST level at day 1 after last injection; control group vs treatment group ;1,66+0,05 vs 0,91+0,12, p value = 0,001. 2 weeks after injection; AST level for both group were become lower 1,12 (1,11-1,22) vs (0,96+0,03); p=0,021), and ALT level on treatment group was significantly lower at day 1 and 2 weeks after injection with p value <0,001 and 0, 033a"