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

• DOI: 10.1016/j.stem.2013.09.015
• Publication Date: 2013-10-17T21:01:09Z
• Authors: Robert P. Fordham; Shiro Yui; Nicholas R.F. Hannan; Christoffer Soend...; Alison Madgwick; Pawel J. Schweiger; Ole H. Nielsen; Ludovic Vallier; Roger A. Pedersen; Tetsuya Nakamura; Mamoru Watanabe; Kim B. Jensen
• Keywords: Pluripotent Stem Cells; 0303 health sciences; Colon; Stem Cells; Cell Differentiation; Cell Biology; Article; Intestines; Adult Stem Cells; Mice; 03 medical and health sciences; Fetus; Spheroids, Cellular; Genetics; Molecular Medicine; Animals; Humans; Regeneration; Intestinal Mucosa; Cell Proliferation; Signal Transduction; Stem Cell Transplantation

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.