Human and mouse tissue-engineered small intestine both demonstrate digestive and absorptive function

被引:75
作者
Grant, Christa N. [1 ,2 ]
Mojica, Salvador Garcia [1 ]
Sala, Frederic G. [1 ]
Hill, J. Ryan [1 ]
Levin, Daniel E. [1 ,2 ]
Speer, Allison L. [1 ,2 ]
Barthel, Erik R. [1 ,2 ]
Shimada, Hiroyuki [4 ]
Zachos, Nicholas C. [3 ]
Grikscheit, Tracy C. [1 ,2 ]
机构
[1] Childrens Hosp Los Angeles, Saban Res Inst, Dev Biol & Regenerat Med Program, Los Angeles, CA 90027 USA
[2] Childrens Hosp Los Angeles, USC Keck Sch Med, Div Pediat Surg, Los Angeles, CA 90027 USA
[3] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol & Hepatol, Baltimore, MD 21205 USA
[4] Childrens Hosp Los Angeles, Dept Pathol, USC Keck Sch Med, Los Angeles, CA 90027 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY | 2015年 / 308卷 / 08期
关键词
tissue engineering; regenerative medicine; intestinal failure; intestinal stem cell; short bowel syndrome; POSTNATAL PROGENITOR CELLS; SHORT-BOWEL SYNDROME; EPITHELIAL-CELLS; MURINE MODEL; IN-VIVO; CDC42; COLON; FORMS; DIFFERENTIATION; LOCALIZATION;
D O I
10.1152/ajpgi.00111.2014
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Short bowel syndrome (SBS) is a devastating condition in which insufficient small intestinal surface area results in malnutrition and dependence on intravenous parenteral nutrition. There is an increasing incidence of SBS, particularly in premature babies and newborns with congenital intestinal anomalies. Tissue-engineered small intestine (TESI) offers a therapeutic alternative to the current standard treatment, intestinal transplantation, and has the potential to solve its biggest challenges, namely donor shortage and life-long immunosuppression. We have previously demonstrated that TESI can be generated from mouse and human small intestine and histologically replicates key components of native intestine. We hypothesized that TESI also recapitulates native small intestine function. Organoid units were generated from mouse or human donor intestine and implanted into genetically identical or immunodeficient host mice. After 4 wk, TESI was harvested and either fixed and paraffin embedded or immediately subjected to assays to illustrate function. We demonstrated that both mouse and human tissue-engineered small intestine grew into an appropriately polarized sphere of intact epithelium facing a lumen, contiguous with supporting mesenchyme, muscle, and stem/progenitor cells. The epithelium demonstrated major ultrastructural components, including tight junctions and microvilli, transporters, and functional brush-border and digestive enzymes. This study demonstrates that tissue-engineered small intestine possesses a well-differentiated epithelium with intact ion transporters/channels, functional brush-border enzymes, and similar ultrastructural components to native tissue, including progenitor cells, whether derived from mouse or human cells.
引用
收藏
页码:G664 / G677
页数:14
相关论文
共 35 条
[1]   Identification of stem cells in small intestine and colon by marker gene Lgr5 [J].
Barker, Nick ;
van Es, Johan H. ;
Kuipers, Jeroen ;
Kujala, Pekka ;
van den Born, Maaike ;
Cozijnsen, Miranda ;
Haegebarth, Andrea ;
Korving, Jeroen ;
Begthel, Harry ;
Peters, Peter J. ;
Clevers, Hans .
NATURE, 2007, 449 (7165) :1003-U1
[2]   Tissue Engineering of the Intestine in a Murine Model [J].
Barthel, Erik R. ;
Speer, Allison L. ;
Levin, Daniel E. ;
Sala, Frederic G. ;
Hou, Xiaogang ;
Torashima, Yasuhiro ;
Wigfall, Clarence M. ;
Grikscheit, Tracy C. .
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2012, (70) :e4279
[3]  
Barthel ER, 2012, REGEN MED, V7, P807, DOI [10.2217/RME.12.91, 10.2217/rme.12.91]
[4]   RENEWAL OF PANETH CELLS IN SMALL INTESTINE OF MOUSE [J].
CHENG, H ;
MERZEL, J ;
LEBLOND, CP .
AMERICAN JOURNAL OF ANATOMY, 1969, 126 (04) :507-&
[5]   Studies of brush border enzymes, basement membrane components, and electrophysiology of tissue-engineered neointestine [J].
Choi, RS ;
Riegler, M ;
Pothoulakis, C ;
Kim, BS ;
Mooney, D ;
Vacanti, M ;
Vacanti, JP .
JOURNAL OF PEDIATRIC SURGERY, 1998, 33 (07) :991-996
[6]   ASSAY OF INTESTINAL DISACCHARIDASES [J].
DAHLQVIST, A .
ANALYTICAL BIOCHEMISTRY, 1968, 22 (01) :99-+
[7]   LOCALIZATION OF MYOSIN, ACTIN, AND TROPOMYOSIN IN RAT INTESTINAL EPITHELIUM - IMMUNOHISTOCHEMICAL STUDIES AT THE LIGHT AND ELECTRON-MICROSCOPE LEVELS [J].
DRENCKHAHN, D ;
GROSCHELSTEWART, U .
JOURNAL OF CELL BIOLOGY, 1980, 86 (02) :475-482
[8]   Intestinal distribution of human Na+/H+ exchanger isoforms NHE-1, NHE-2, and NHE-3 mRNA [J].
Dudeja, PK ;
Rao, DD ;
Syed, I ;
Joshi, V ;
Dahdal, RY ;
Gardner, C ;
Risk, MC ;
Schmidt, L ;
Bavishi, D ;
Kim, KE ;
Harig, JM ;
Goldstein, JL ;
Layden, TJ ;
Ramaswamy, K .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 1996, 271 (03) :G483-G493
[9]  
EVANS GS, 1992, J CELL SCI, V101, P219
[10]   Current Concepts: Intestinal Transplantation. [J].
Fishbein, Thomas M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2009, 361 (10) :998-1008