Intestinal Regeneration
Short bowel syndrome is a life-threatening condition characterized by the functional loss of a large proportion of the small bowel. It continues to be an unmet clinical need despite progress in the surgical field, and parenteral nutrition and transplantat
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Tracy Grikscheit and Paolo De Coppi
Abbreviations
Introduction
BMP CBCCs ENS ESCs FGF GLP-2 Ihh iPSCs ISCs OUs PDGF PGA PLLA SBS Shh TA TESI TPN VEGF
The small intestine is a vital organ that achieves homeostasis through tissue growth and maintenance. Its loss may lead to variable degrees of absorption debilities, such as short bowel syndrome (SBS). In previous chapters, we have looked at alternative therapeutic options to treat SBS; however, this is an area of unmet clinical need. While strategies such as the increase of intestinal surface area could help by partly restoring the absorption level to that of the healthy organ, at the moment only total parenteral nutrition (TPN) and bowel transplantation are real long-term options for these patients. However, as discussed in this volume, TPN is associated with line infections, deep venous thrombosis, and liver failure, while intestinal transplantation is limited by organ shortage and the need for immunosuppression. Therefore, there is a need for innovative solutions which would allow a better quality of life and a higher survival rate for patients with SBS [1]. The intestine, similar to other epithelial organs, undergoes constant epithelial renewal, thanks to the presence of highly proliferative resident stem cells. Intestinal stem cells (ISCs) are present in the crypt and maintain the pool of precursor and differentiated cells, which are shed from the tip of the villi after a journey of 7–10 days from their production at the base of the crypt [2]. This highly specified environment,
Bone morphogenetic protein Crypt base columnar cells Enteric nervous system Embryonic stem cells Fibroblast growth factor Glucagon-like peptide-2 Indian hedgehog Induced pluripotent stem cells Intestinal stem cells Organoid units Platelet-derived growth factor Polyglycolic acid Poly-l-lactic acid Short bowel syndrome Sonic hedgehog Transit amplifying Tissue-engineered small intestine Total parenteral nutrition Vascular endothelial growth factor
T. Grikscheit, MD, PhD Developmental Biology and Regenerative Medicine Program, Saban Research Institute, Children’s Hospital Los Angeles, Los Angeles, CA, USA P. De Coppi, MD, PhD (*) Stem Cells and Regenerative Medicine, DBC, Institute of Child Health, University College London, and Great Ormond St. Hospital for Children, 30 Guilford Street, London WC1N 1EH, UK e-mail: [email protected]
© Springer International Publishing Switzerland 2016 R.J. Rintala et al. (eds.), Current Concepts of Intestinal Failure, DOI 10.1007/978-3-319-42551-1_12
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Cell isolation Biomolecules
Implantation
Biorectors
Natural or synthetic scaffold
Fig. 12.1 Tissue engineering. A tissue-engineered intestinal construct may be created by the combination of a scaffold and cells, grown in a bioreactor and transplanted in patients. A three-dimensional scaffold may be created from synthetic material, collagen, or a decellularized
matrix. Cells for the use of tissue engineering are derived from a number of sources such as t
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