Back to 2011 Program

We have previously shown that mesenchymal stem cells (MSC) improve anal sphincter pressures after injury. We aim to demonstrate MSC homing to the injured anal sphincter by comparing anal sphincter pressures following IM MSC injection and serial IV MSC infusion in a rat model of acute anal sphincter injury.Method: 45 virgin rats were divided into injury (n=35) and no injury (NI, n=10) groups. The injury group was divided into saline(PBS) or MSC treatment and a control group (n=5) which received no treatment. Each treatment group was further divided into IM and serial IV (n=5) group . The MSC IM and IV (n=5) and control groups were followed up for 5 weeks The injury was a partial anal sphincter excision(PSE) of 25% of the anal sphincter. Anal pressures were recorded prior, 10 days and 5 weeks after treatment with a balloon connected to a digital recorder. 24 hours after injury, the animals received 5x106 labeled MSC or 0.2ml saline into the anal sphincter for IM treatment , while IV treatment group received the same dose daily for 6 consecutive days via the tail vein. Anal sphincters were harvested and submitted for Masson’s staining. Results: 10 days after IM treatment, significant increase in resting (P<0.001) and peak pressures (P<0.001) was seen after MSC treatment when compared with PBS after injury . (9.78±0.84, 13.13±1.2, respectively) vs. (6.23±0.48, 8.32±0.64, respectively).When compared with the NI group and MSC treatment, recovery of the anal pressures was not complete (resting (P=0.04) and peak pressures (P=0.02). The IV infusion group showed significantly increased resting (P<0.001) and peak pressures (P<0.001) in MSC treated animals compared with PBS (11.03±0.71, 16.68±1.33, respectively) vs. (6.94±0.28, 8.56±0.34, respectively) after injury(Figure). However recovery was complete and no significant difference was seen pressures when compared to NI group.At 5 weeks after IM treatment significant peak pressures (P=<0.001) after MSC treatment were seen compared to NI group. However, after IV treatment significant resting (P=0.01) and peak pressures (P=<0.001) were seen compared to NI group Marked decrease in fibrosis and scar tissue was seen in the MSC treated group (See Figure),Conclusion: Although IM MSC treatment after injury causes increase in anal pressures it is not sustained at 5 weeks . MSC home after serial IV infusion to the injured anal sphincter causing increase in the anal sphincter pressures which are comparable to sham treatment and increase till 5 weeks. Healing is by fibrosis in the control animals while the MSC treated group showed less scarring with IV infusion group showing the least scarring.