Intra-uterine injection of amnion-derived acellular bioscaffold product in mares

Amnion-derived acellular bioscaffold product (ADABP) has been used as an anti-inflammatory agent to promote healing in human and veterinary medicine. Proteins and cytokines present in ADABP are reported to decrease fibroblast formation and fibrosis.1 Thus, ADABP may be beneficial in the treatment of uterine adhesions, uterine cyst ablations, and remodeling of scar tissue. The safety of uterine injection of ADABP is unknown. We studied the systemic and uterine effects after uterine injection. Twelve clinically healthy light-breed mares (mean age 11.5 years; range 5 – 22) were the subjects. Rectal temperature and behavior were recorded for the duration of the study. On day0, all mares underwent a hysteroscopic examination, control mares (n = 3) received 3 ml injection of sterile saline in the base of 1 uterine horn, and AniCell mares (n = 9) received 3 ml of ADABP (EquusCell StemWrap D™, AniCell Biotech, Arizona) in the base of 1 uterine horn. Blood (for serum amyloid A[SAA], fibrinogen [FIB], and white blood cell count [WBC]), endometrial cytology, and aerobic cultures were obtained prior to hysteroscopy. Four days (day 4) after injection, mares were evaluated via transrectal ultrasonography, and blood was obtained. Twenty-one days (day 21) after injection, endometrial cytology, aerobic culture, and hysteroscopy were performed. Continuous data were analyzed to determine the main effects of group, day, and their interaction using the SAS MIXED procedure with a repeated statement. Categorical data were analyzed using the SAS LOGISTIC procedure. No mares experienced an elevation in rectal temperature during the 21 days after injection. There were no differences in bloodwork for markers of inflammation(SAA, FIB, WBC) from day 0 to day 4 either in the control or AniCell group. Similarly, there were no differences in uterine cytology and culture results between groups or among days within groups. Hysteroscopy following injection demonstrated no gross evidence of detrimental effects in any mare examined. In 1 mare that received a saline injection, a small 1 cm bleb of fibrous tissue was noticed and that remained for 21 days after injection. This study demonstrated that ADABP had no detrimental effect on the systemic health of the mare and it is as safe as hysteroscopy and saline intrauterine injection up to21 days after injection. Further work is continuing, evaluating histological changes in the mares’ endometrium after injection and in clinical cases where the injection is performed into uterine tissue, as ADABP may be a useful tool to promote endometrial healing in the mare.

Keywords: Amnion-derived cell product, endometritis, hysteroscopy, uterine injection

Reference1. Mamede AC, Carvalho MJ, Abrantes AM, et al: Amniotic membrane: from structure and functions to clinical application. Cell and Tissue Res 2012;349:447-458.