Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury

TY - JOUR

T1 - Transplantation of Expanded Fetal Intestinal Progenitors Contributes to Colon Regeneration after Injury

AU - Fordham, Robert P

AU - Yui, Shiro

AU - Hannan, Nicholas R F

AU - Soendergaard, Christoffer

AU - Madgwick, Alison

AU - Schweiger, Pawel J

AU - Nielsen, Ole H

AU - Vallier, Ludovic

AU - Pedersen, Roger A

AU - Nakamura, Tetsuya

AU - Watanabe, Mamoru

AU - Jensen, Kim B

N1 - Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2013/12/5

Y1 - 2013/12/5

N2 - Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region-specific differentiation markers. This work provides insight into mechanisms underlying development of the mammalian intestine and points to future opportunities for patient-specific regeneration of the digestive tract.

AB - Regeneration and homeostasis in the adult intestinal epithelium is driven by proliferative resident stem cells, whose functional properties during organismal development are largely unknown. Here, we show that human and mouse fetal intestine contains proliferative, immature progenitors, which can be expanded in vitro as Fetal Enterospheres (FEnS). A highly similar progenitor population can be established during intestinal differentiation of human induced pluripotent stem cells. Established cultures of mouse fetal intestinal progenitors express lower levels of Lgr5 than mature progenitors and propagate in the presence of the Wnt antagonist Dkk1, and new cultures can be induced to form mature intestinal organoids by exposure to Wnt3a. Following transplantation in a colonic injury model, FEnS contribute to regeneration of colonic epithelium by forming epithelial crypt-like structures expressing region-specific differentiation markers. This work provides insight into mechanisms underlying development of the mammalian intestine and points to future opportunities for patient-specific regeneration of the digestive tract.

U2 - 10.1016/j.stem.2013.09.015

DO - 10.1016/j.stem.2013.09.015

M3 - Journal article

C2 - 24139758

SN - 1934-5909

VL - 13

SP - 734

EP - 744

JO - Cell Stem Cell

JF - Cell Stem Cell

IS - 6

ER -