Molecular Manipulations and Intestinal Stem Cell-Derived Organoids in Inflammatory Bowel Disease

被引：10

作者：

Boye, Theresa Louise ^{[1
]}

Steenholdt, Casper ^{[1
]}

Jensen, Kim Bak ^{[2
,3
]}

Nielsen, Ole Haagen ^{[1
]}

机构：

[1] Univ Copenhagen, Herlev Hosp, Dept Gastroenterol, Borgmester Ib,Juuls Vej 1, DK-2730 Herlev, Denmark

[2] Univ Copenhagen, Novo Nordisk Fdn Ctr Stem Cell Med, Fac Hlth & Med Sci, Copenhagen, Denmark

[3] Univ Copenhagen, Biotech Res & Innovat Ctr BRIC, Copenhagen, Denmark

来源：

STEM CELLS | 2022年 / 40卷 / 05期

关键词：

CRISPR; Cas9; system; DNA methylation; epigenetics; histone modification; inflammatory bowel disease; intestinal stem cells; organoids; BUTYRATE-PRODUCING BACTERIA; DNA METHYLATION; ULCERATIVE-COLITIS; CHROMATIN ACCESSIBILITY; EPITHELIAL-CELLS; HUMAN COLON; IN-VITRO; CROHNS; GENETICS; DIAGNOSIS;

D O I：

10.1093/stmcls/sxac014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

The pathogenesis of inflammatory bowel diseases (IBD) involves genetic predisposition, environmental factors, and a broadly dysregulated intestinal immune response to the commensal intestinal microflora. The interface between genetic predisposition and environmental factors is reflected in the epigenetic regulation at the transcriptional level. Treatment targets now involve mucosal and histological healing, but the future might additionally include normalization of intestinal cellular functions also at the molecular level, for example comprising complete restoration of phenotypic, genotypic, and epigenetic states. Recent developments in patient-derived epithelial intestinal stem cell (ISC) organoid technologies have opened exciting new therapeutic opportunities to potentially attain molecular healing by combining stem cell therapy with molecular manipulations using (epi)drugs and/or CRISPR/Cas9 genome editing. Here, we are the first to discuss the possibility for phenotypic, genotypic, and epigenetic restoration via molecular manipulations and stem cell therapy in IBD from a clinical perspective.

引用

页码：447 / 457

页数：11

共 89 条

[61] Diagnosis of Ulcerative Colitis Before Onset of Inflammation by Multivariate Modeling of Genome-wide Gene Expression Data [J].

Olsen, Jorgen ;

Gerds, Thomas A. ;

Seidelin, Jakob B. ;

Csillag, Claudio ;

Bjerrum, Jacob T. ;

Troelsen, Jesper T. ;

Nielsen, Ole Haagen .

INFLAMMATORY BOWEL DISEASES, 2009, 15 (07) :1032-1038

[62] Gene activation precedes DNA demethylation in response to infection in human dendritic cells [J].

Pacis, Alain ;

Mailhot-Leonard, Florence ;

Tailleux, Ludovic ;

Randolph, Haley E. ;

Yotova, Vania ;

Dumaine, Anne ;

Grenier, Jean-Christophe ;

Barreiro, Luis B. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (14) :6938-6943

[63] A microbial signature for Crohn's disease [J].

Pascal, Victoria ;

Pozuelo, Marta ;

Borruel, Natalia ;

Casellas, Francesc ;

Campos, David ;

Santiago, Alba ;

Martinez, Xavier ;

Varela, Encarna ;

Sarrabayrouse, Guillaume ;

Machiels, Kathleen ;

Vermeire, Severine ;

Sokol, Harry ;

Guarner, Francisco ;

Manichanh, Chaysavanh .

GUT, 2017, 66 (05) :813-822

[64] Defining Disease Severity in Inflammatory Bowel Diseases: Current and Future Directions [J].

Peyrin-Biroulet, Laurent ;

Panes, Julian ;

Sandborn, William J. ;

Vermeire, Severine ;

Danese, Silvio ;

Feagan, Brian G. ;

Colombel, Jean-Frederic ;

Hanauer, Stephen B. ;

Rycroft, Beth .

CLINICAL GASTROENTEROLOGY AND HEPATOLOGY, 2016, 14 (03) :348-+

[65] Is histological healing a feasible endpoint in ulcerative colitis? [J].

Rath, Timo ;

Atreya, Raja ;

Neurath, Markus F. .

EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY, 2021, 15 (06) :665-674

[66] Colonic microbiota is associated with inflammation and host epigenomic alterations in inflammatory bowel disease [J].

Ryan, F. J. ;

Ahern, A. M. ;

Fitzgerald, R. S. ;

Laserna-Mendieta, E. J. ;

Power, E. M. ;

Clooney, A. G. ;

O'Donoghue, K. W. ;

McMurdie, P. J. ;

Iwai, S. ;

Crits-Christoph, A. ;

Sheehan, D. ;

Moran, C. ;

Flemer, B. ;

Zomer, A. L. ;

Fanning, A. ;

O'Callaghan, J. ;

Walton, J. ;

Temko, A. ;

Stack, W. ;

Jackson, L. ;

Joyce, S. A. ;

Melgar, S. ;

DeSantis, T. Z. ;

Bell, J. T. ;

Shanahan, F. ;

Claesson, M. J. .

NATURE COMMUNICATIONS, 2020, 11 (01)

[67] Human DNA methylomes of neurodegenerative diseases show common epigenomic patterns [J].

Sanchez-Mut, J. V. ;

Heyn, H. ;

Vidal, E. ;

Moran, S. ;

Sayols, S. ;

Delgado-Morales, R. ;

Schultz, M. D. ;

Ansoleaga, B. ;

Garcia-Esparcia, P. ;

Pons-Espinal, M. ;

de lagran, M. M. ;

Dopazo, J. ;

Rabano, A. ;

Avila, J. ;

Dierssen, M. ;

Lott, I. ;

Ferrer, I. ;

Ecker, J. R. ;

Esteller, M. .

TRANSLATIONAL PSYCHIATRY, 2016, 6 :e718-e718

[68] Induced organoids derived from patients with ulcerative colitis recapitulate colitic reactivity [J].

Sarvestani, Samaneh K. ;

Signs, Steven ;

Hu, Bo ;

Yeu, Yunku ;

Feng, Hao ;

Ni, Ying ;

Hill, David R. ;

Fisher, Robert C. ;

Ferrandon, Sylvain ;

DeHaan, Reece K. ;

Stiene, Jennifer ;

Cruise, Michael ;

Hwang, Tae Hyun ;

Shen, Xiling ;

Spence, Jason R. ;

Huang, Emina H. .

NATURE COMMUNICATIONS, 2021, 12 (01)

[69]

Sarvestani Samaneh K, 2018, Oncotarget, V9, P28717, DOI 10.18632/oncotarget.25617

[70] Growing Self-Organizing Mini-Guts from a Single Intestinal Stem Cell: Mechanism and Applications [J].

Sato, Toshiro ;

Clevers, Hans .

SCIENCE, 2013, 340 (6137) :1190-1194

← 1 2 3 4 5 6 7 8 9 →