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The effect of dosing of Stromal Cell Derived Factor 1 on anal sphincter regeneration

Tissue Eng Part A. 2022 Nov 7. doi: 10.1089/ten.TEA.2022.0149. Online ahead of print.


The aim of this study is to investigate if a high dose of the SDF -1 plasmid improves outcome in a minipig model of chronic anal sphincter injury.

METHODS: Twenty two female minipigs underwent excision of the posterior hemi-circumference of the anal sphincter complex and were allowed to recover for 6 weeks. They were randomly allocated (n=6) to receive either 5% dextrose (sham), or 2, 4 or 8 mg of SDF-1 plasmid at the defect site. Two control pigs received no surgery/treatment. Outcome measures included anal manometry at pre-injury/pre-treatment and 2, 4 and 8 weeks after treatment, recording the mean of 8 pressure channels and the posterior channel alone, histopathology using Masson’s trichrome and immunohistochemistry using PGP9.5 for staining of neural structures and CY3 staining for blood vessels. Data is expressed as mean±standard error. Manometry analysis used two-way ANOVA followed by the Holm-Sidak test. Quantification of muscle/fibrosis was analyzed with a Kruskal-Wallis One Way Analysis of Variance on Ranks.

RESULTS: Posterior anal pressures were significantly decreased in sham treated animals compared to controls (p=0.04). In contrast, mean anal pressures at the 4 time points were not significantly different between groups. (p>0.05) The defect area of the sham treated group showed irregular muscle bundles while all three SDF-1 treatment groups show organized muscle bundles with the most organization in the higher dose groups. Quantification of Masson stained slides showed no statistically significant differences between groups but did show increased muscle volume in the area of defect in the treatment groups compared to sham. PGP9.5 and CY3 staining showed increased fluorescence in the higher dose groups compared to sham treatment.

CONCLUSION: A single higher dose of the plasmid encoding SDF-1 may increase muscle volume in the area of a chronic defect.

PMID:36341592 | DOI:10.1089/ten.TEA.2022.0149

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