title: Concise Review: The Potential Use of Intestinal Stem Cells to Treat Patients with Intestinal Failure.
abstract: Intestinal failure is a rare life-threatening condition that results in the inability to maintain normal growth and hydration status by enteral nutrition alone. Although parenteral nutrition and whole organ allogeneic transplantation have improved the survival of these patients, current therapies are associated with a high risk for morbidity and mortality. Development of methods to propagate adult human intestinal stem cells (ISCs) and pluripotent stem cells raises the possibility of using stem cell-based therapy for patients with monogenic and polygenic forms of intestinal failure. Organoids have demonstrated the capacity to proliferate indefinitely and differentiate into the various cellular lineages of the gut. Genome-editing techniques, including the overexpression of the corrected form of the defective gene, or the use of CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 to selectively correct the monogenic disease-causing variant within the stem cell, make autologous ISC transplantation a feasible approach. However, numerous techniques still need to be further optimized, including more robust ex vivo ISC expansion, native ISC ablation, and engraftment protocols. Large-animal models can to be used to develop such techniques and protocols and to establish the safety of autologous ISC transplantation because outcomes in such models can be extrapolated more readily to humans. Stem Cells Translational Medicine 2017;6:666-676.
authors.affiliation: Division of Gastroenterology and Nutrition, Department of Pediatrics, Mattel Children's Hospital and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.|Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Sung Noh
authors.initials: SN
authors.lastname: Hong
authors.affiliation: Division of Pediatric Surgery, Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: James C Y
authors.initials: JC
authors.lastname: Dunn
authors.affiliation: Department of Surgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.|Department of Surgery, Veterans Administration Greater Los Angeles Health System, Los Angeles, California, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Stelzner
authors.affiliation: Division of Gastroenterology and Nutrition, Department of Pediatrics, Mattel Children's Hospital and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
authors.forename: Martín G
authors.initials: MG
authors.lastname: Martín
mesh_terms: D000818:Animals; D064113:CRISPR-Cas Systems; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D000072669:Gene Editing / Q000379:methods*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007422:Intestines / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation*; D020127:Recovery of Function; D012038:Regeneration; D012307:Risk Factors; D012778:Short Bowel Syndrome / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D015398:Signal Transduction; D033581:Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
keywords: Congenital diarrhea; Congenital tufting enteropathy; Intestinal failure; Intestinal stem cell; Microvillus inclusion disease