Abstract
Background Mesenchymal stem cells (MSCs) are valuable in regenerative medicine, and MSC culture
supernatant (MSC-CS) reportedly inhibits inflammation and fibrosis. We investigated
whether colorectal luminal stricture develops after circumferential endoscopic submucosal
dissection (ESD) in the colorectum, and whether the development of luminal stricture
could be prevented by using MSC-CS enema.
Methods In the first experiment, we performed circumferential ESD in the rectums or distal
colons of pigs (n = 4 in each group). We sacrificed the pigs on Day 22 and measured
the degree of luminal stricture. In the second experiment, we performed circumferential
ESD in the rectums of pigs and administered an MSC-CS gel or a control gel enema after
ESD for 4 days. We sacrificed the pigs on Day 8 (n = 3 in each group) or 22 (n = 3
in each group) to measure the degree of luminal stricture, and performed histological
analysis.
Results Severe luminal stricture was observed in the rectum but not in the distal colon.
Moreover, fiber accumulation in the submucosa and hypertrophy of the muscularis propria
were observed in the rectum but not in the distal colon. The degree of luminal stricture
in the rectum was significantly lower in the MSC-CS group than in the control group. Furthermore,
MSC-CS attenuated myofibroblast activation and hypertrophy of the muscularis propria
on Day 22, and reduced inflammatory cell infiltration on Day 8.
Conclusions Luminal stricture after ESD developed only in the rectum because of the difference
in myofibroblast activation and fiber accumulation. In addition, MSC-CS enema prevented
luminal stricture after ESD, possibly by inhibiting the inflammatory reaction and
fibrosis.
