Autologous Hematopoietic Stem Cell Therapy in Liver Cirrhosis

  • Slides: 20
Download presentation
소화기내과 목요세미나 Autologous Hematopoietic Stem Cell Therapy in Liver Cirrhosis 이 윤 빈

소화기내과 목요세미나 Autologous Hematopoietic Stem Cell Therapy in Liver Cirrhosis 이 윤 빈

Stem Cells § Definition of stem cell § Self-renewal: the ability to go through

Stem Cells § Definition of stem cell § Self-renewal: the ability to go through numerous cycles of cell division § Potency: the capacity to differentiate into specialized cell types Omnipotent / Pluripotent / Multipotent / Oligopotent / Unipotent Bone Marrow-derived Stem Cells Adipose Stem Cells Embryonic Stem Cells ES cells Placenta Stem Cells Cord Blood Stem Cells Fetal Stem Cells Induced Pluripotent Stem Cells i. PSCs

Embryonic Stem Cells § From inner cell mass (ICM) in pre-implanted blastocyst § 1981,

Embryonic Stem Cells § From inner cell mass (ICM) in pre-implanted blastocyst § 1981, from mouse § 1998, from human § Characteristics § Self-renewal § Pluripotency § Clonality Evans MJ, Kaufman MH. Nature 1981; 292: 154 -6 Thomson JA et al. Science 1998; 282: 1145 -7

Induced Pluripotent Stem Cells § Reprogramming of somatic cells with four defined transcription factors

Induced Pluripotent Stem Cells § Reprogramming of somatic cells with four defined transcription factors § § Oct 3/4 Sox 2 Klf 4 c-Myc Shinya Yamanaka Nobel Prize in Physiology and Medicine, 2012 Takahashi K, Yamanaka S. Cell 2006; 126: 663 -76

Adult Stem Cells § § From various tissues – “resident” stem cells Called as

Adult Stem Cells § § From various tissues – “resident” stem cells Called as “somatic stem cells” Multipotent – restricted to differentiation Trans-differentiation § Types of adult stem cells § § § Hematopoietic stem cells Neural stem cells Satellite cells (Skeletal stem cells) Cord blood-derived stem cells Mesenchymal stem cells

Bone Marrow–Derived Stem Cell Subpopulations Houlihan DD et al. Gastroenterology 2008; 135: 438 -50

Bone Marrow–Derived Stem Cell Subpopulations Houlihan DD et al. Gastroenterology 2008; 135: 438 -50

G-CSF Therapy in Acute-on-Chronic Liver Failure § N=47, Randomized controlled trial § India §

G-CSF Therapy in Acute-on-Chronic Liver Failure § N=47, Randomized controlled trial § India § December 2008–August 2010 § 5 μg/kg G-CSF subcutaneously (12 doses; group A, n=23) or placebo (group B, n=24) plus standard medical therapy Garg V et al. Gastroenterology 2012; 142: 505– 512

Purified (c-kit+/sca 1+/lin-) HSCs and S 1 P Inhibition αSMA staining Picrosirius red staining

Purified (c-kit+/sca 1+/lin-) HSCs and S 1 P Inhibition αSMA staining Picrosirius red staining King A et al. Gastroenterology 2017; 153: 233 -248

Newsome PN et al. Lancet Gastroenterol Hepatol 2018; 3: 25– 36 Guo C et

Newsome PN et al. Lancet Gastroenterol Hepatol 2018; 3: 25– 36 Guo C et al. Clinical Gastroenterology and Hepatology 2019; 17: 1175– 1182

Stem Cell Research in Liver Diseases § Type and source of stem cells §

Stem Cell Research in Liver Diseases § Type and source of stem cells § HSC vs Mesenchymal stem cells vs Pluripotent stem cells § Autologous vs Allogeneic § Clinical translation § Stem cell transplantation vs Organoids § Disease modeling and mechanistic study § Optimal indication of stem cell therapy § End-stage liver disease § Compensated liver cirrhosis § Nonalcoholic fatty liver disease § Adequate endpoints in clinical trials

Bone Marrow-derived Mesenchymal Stem Cells Effect of MSCs and MDHs on histopathological changes in

Bone Marrow-derived Mesenchymal Stem Cells Effect of MSCs and MDHs on histopathological changes in recipient liver Mesenchymal stem cell–derived hepatocyte Changes in No. of donor-derived cells in recipient liver Direct differentiation into functional hepatocytes << Paracrine effect Kuo TK et al. Gastroenterology 2008; 134: 2111 -21

BM-MSCs: Phase 2 Clinical Trial Suk KT and Yoon JH et al. Hepatology 2016;

BM-MSCs: Phase 2 Clinical Trial Suk KT and Yoon JH et al. Hepatology 2016; 64: 2185 -2197

BM-MSCs: Phase 2 Clinical Trial Suk KT and Yoon JH et al. Hepatology 2016;

BM-MSCs: Phase 2 Clinical Trial Suk KT and Yoon JH et al. Hepatology 2016; 64: 2185 -2197

Placenta-Derived Stem Cells § Characteristics and Advantages of PDSCs § Great potential for proliferation,

Placenta-Derived Stem Cells § Characteristics and Advantages of PDSCs § Great potential for proliferation, differentiation, and self-renewal § Readily available and easily procured without invasive procedures § Massive numbers and have strong immunologic privileges § Classification of PDSCs § § Chorionic plate-derived MSCs (CP-MSCs) Amniotic MSCs (AMSCs) Chorionic villi-derived MSCs (CV-MSCs) Wharton’s jelly derived MSCs (WJ-MSCs) Lee MJ et al. J Cell Biochem 2010; 111: 1453– 1463

CP-MSCs: Preclinical Studies Rat model of CCl 4 -induced liver injury Lee MJ et

CP-MSCs: Preclinical Studies Rat model of CCl 4 -induced liver injury Lee MJ et al. J Cell Biochem. 2010; 111: 1453– 1463

CP-MSCs: Preclinical Studies Rat model of bile duct ligation CP-MSCs WI-38 Lee YB et

CP-MSCs: Preclinical Studies Rat model of bile duct ligation CP-MSCs WI-38 Lee YB et al. Stem Cells Int. 2017; 2017: 5180579

CP-MSCs in NAFLD High-fat diet (HFD)-fed mouse model Lee YB et al. Unpublished Data

CP-MSCs in NAFLD High-fat diet (HFD)-fed mouse model Lee YB et al. Unpublished Data

Liver Bud Takanori Takebe Nature 2013; 499: 481 -4 Nature 2017; 546: 533 -538

Liver Bud Takanori Takebe Nature 2013; 499: 481 -4 Nature 2017; 546: 533 -538

Stem Cell Research in Liver Diseases § Type and source of stem cells §

Stem Cell Research in Liver Diseases § Type and source of stem cells § HSC vs Mesenchymal stem cells vs Pluripotent stem cells § Autologous vs Allogeneic § Clinical translation § Stem cell transplantation vs Organoids § Disease modeling and mechanistic study § Optimal indication of stem cell therapy § End-stage liver disease § Compensated liver cirrhosis § Nonalcoholic fatty liver disease § Adequate endpoints in clinical trials