The Development of Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) During Gastric Repair Is Absent in the Aged Stomach

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• 作者：Amy C. Engevik¹ ; Rui Feng¹ ; Eunyoung Choi² ; Shana White³ ; Nina Bertaux-Skeirik¹ ; Jing Li¹ ; Maxime M. Mahe⁴ ; Eitaro Aihara¹ ; Li Yang¹ ; Betsy DiPasquale⁵ ; Sunghee Oh⁶ ; Kristen A. Engevik¹ ; Andrew S. Giraud⁷ ; Marshall H. Montrose¹ ; Mario Medvedovic³ ; Michael A. Helmrath⁴ ; James R. Goldenring² ; ^§ ; ; ^{jim.goldenring@vanderbilt.edu" class="auth_mail" title="E-mail the corresponding author} ; Yana Zavros¹ ; ^§ ; ; ^{yana.zavros@uc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Epithelial Regeneration ; Gastric Cancer ; Human Gastric Organoids ; CD44v
• 刊名：CMGH Cellular and Molecular Gastroenterology and Hepatology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：2
• 期：5
• 页码：605-624
• 全文大小：12928 K

文摘

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.