TY - JOUR
T1 - The Development of Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) During Gastric Repair Is Absent in the Aged Stomach
AU - Engevik, Amy C.
AU - Feng, Rui
AU - Choi, Eunyoung
AU - White, Shana
AU - Bertaux-Skeirik, Nina
AU - Li, Jing
AU - Mahe, Maxime M.
AU - Aihara, Eitaro
AU - Yang, Li
AU - DiPasquale, Betsy
AU - Oh, Sunghee
AU - Engevik, Kristen A.
AU - Giraud, Andrew S.
AU - Montrose, Marshall H.
AU - Medvedovic, Mario
AU - Helmrath, Michael A.
AU - Goldenring, James R.
AU - Zavros, Yana
N1 - Publisher Copyright:
© 2016 The Authors
PY - 2016
Y1 - 2016
N2 - Background & Aims During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2–expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration. Methods Acetic acid ulcers were induced in young (2–3 mo) and aged (18–24 mo) C57BL/6 mice to determine the quality of ulcer repair with advancing age. Yellow chameleon 3.0 mice were used to generate yellow fluorescent protein–expressing organoids for transplantation. Yellow fluorescent protein–positive gastric organoids were transplanted into the submucosa and lumen of the stomach immediately after ulcer induction. Gastric tissue was collected and analyzed to determine the engraftment of organoid-derived cells within the regenerating epithelium. Results Wound healing in young mice coincided with the emergence of SPEM within the ulcerated region, a response that was absent in the aged stomach. Although aged mice showed less metaplasia surrounding the ulcerated tissue, organoid-transplanted aged mice showed regenerated gastric glands containing organoid-derived cells. Organoid transplantation in the aged mice led to the emergence of SPEM and gastric regeneration. Conclusions These data show the development of SPEM during gastric repair in response to injury that is absent in the aged stomach. In addition, gastric organoids in an injury/transplantation mouse model promoted gastric regeneration.
AB - Background & Aims During aging, physiological changes in the stomach result in more tenuous gastric tissue that is less capable of repairing injury, leading to increased susceptibility to chronic ulceration. Spasmolytic polypeptide/trefoil factor 2–expressing metaplasia (SPEM) is known to emerge after parietal cell loss and during Helicobacter pylori infection, however, its role in gastric ulcer repair is unknown. Therefore, we sought to investigate if SPEM plays a role in epithelial regeneration. Methods Acetic acid ulcers were induced in young (2–3 mo) and aged (18–24 mo) C57BL/6 mice to determine the quality of ulcer repair with advancing age. Yellow chameleon 3.0 mice were used to generate yellow fluorescent protein–expressing organoids for transplantation. Yellow fluorescent protein–positive gastric organoids were transplanted into the submucosa and lumen of the stomach immediately after ulcer induction. Gastric tissue was collected and analyzed to determine the engraftment of organoid-derived cells within the regenerating epithelium. Results Wound healing in young mice coincided with the emergence of SPEM within the ulcerated region, a response that was absent in the aged stomach. Although aged mice showed less metaplasia surrounding the ulcerated tissue, organoid-transplanted aged mice showed regenerated gastric glands containing organoid-derived cells. Organoid transplantation in the aged mice led to the emergence of SPEM and gastric regeneration. Conclusions These data show the development of SPEM during gastric repair in response to injury that is absent in the aged stomach. In addition, gastric organoids in an injury/transplantation mouse model promoted gastric regeneration.
KW - CD44v
KW - Epithelial Regeneration
KW - Gastric Cancer
KW - Human Gastric Organoids
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U2 - 10.1016/j.jcmgh.2016.05.004
DO - 10.1016/j.jcmgh.2016.05.004
M3 - Article
AN - SCOPUS:84997419129
SN - 2352-345X
VL - 2
SP - 605
EP - 624
JO - CMGH
JF - CMGH
IS - 5
ER -