title: Human tissue-engineered small intestine forms from postnatal progenitor cells.
abstract: OBJECTIVE
  Tissue-engineered small intestine (TESI) represents a potential cure for short bowel syndrome (SBS). We previously reported full-thickness intestine formation using an organoid units-on-scaffold approach in rodent and swine models. Transplanted intestinal xenografts have been documented to survive from human fetal tissue but not from postnatal tissue. We now present the first report of human TESI from postnatal tissue.
  
  
  METHODS
  Organoid units (OU) were prepared from human small bowel resection specimens, loaded onto biodegradable scaffolds and implanted into NOD/SCID gamma chain-deficient mice. After 4 weeks, TESI was harvested and immunostained for β2-microglobulin to identify human tissue, villin for enterocytes, lysozyme for Paneth cells, chromogranin-A for enteroendocrine cells, mucin-2 for goblet cells, smooth muscle actin and desmin to demonstrate muscularis, and S-100 for nerves.
  
  
  RESULTS
  All TESI was of human origin. Immunofluorescence staining of human TESI reveals the presence of all four differentiated cell types of mature human small intestine, in addition to the muscularis and the supporting intestinal subepithelial myofibroblasts. Nerve tissue is also present.
  
  
  CONCLUSIONS
  Our technique demonstrates survival, growth, and differentiation of postnatally derived human small intestinal OU into full thickness TESI in murine hosts. This regenerative medicine strategy may eventually assist in the treatment of SBS.
authors: Division of Pediatric Surgery, Children's Hospital Los Angeles, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90027, USA.
authors: Daniel E
authors: DE
authors: Levin
authors: Erik R
authors: ER
authors: Barthel
authors: Allison L
authors: AL
authors: Speer
authors: Frédéric G
authors: FG
authors: Sala
authors: Xiaogang
authors: X
authors: Hou
authors: Yasuhiro
authors: Y
authors: Torashima
authors: Tracy C
authors: TC
authors: Grikscheit
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D015415:Biomarkers / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D007421:Intestine, Small / Q000033:anatomy & histology / Q000254:growth & development* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009940:Organoids / Q000637:transplantation*; D012778:Short Bowel Syndrome / Q000601:surgery; D023822:Tissue Engineering / Q000295:instrumentation / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D001672:Biocompatible Materials; D015415:Biomarkers