Autocross-linked hyaluronic acid gel and adipose-derived mesenchymal stem cell composites for the treatment intrauterine adhesions

Abstract

Objective: To evaluate the effect of adding adipose-derived mesenchymal stem cells (ASCs) to autocross-linked hyaluronic acid (HA) gel for intrauterine adhesion (IUA) treatment. Methods: A rat IUA model was established by mechanical curettage and infection, and then different treatments were administered to the rats on day 7 after modeling. Ninety-six rats were randomly divided into the following groups: IUA model group, gel therapy group, and combination therapy group (HA gel combined with ASCs). Eight rats per group were sacrificed on days 7, 10, 14 and 21 for the subsequent experiments. Morphological changes were determined by hematoxylin-eosin staining and Masson staining. Smad3 and leukocyte inhibitory factor (LIF) were analyzed by quantitative real-time polymerase chain reaction and immunohistochemistry. Results: The endometrial lines in the gel therapy group and the combination therapy group were more complete than those in the model group. Masson staining showed that fibrosis area rates in the gel therapy group and the combination therapy group were significantly lower than those in the model group on day 7(P < 0.05). During the observation period, the fibrosis area rates in the combination therapy group remained lower than those in the model group (P < 0.05). The mRNA expression of Smad3 in the combination therapy group was lower than that in the model group and gel therapy group during the observation period (P < 0.05). The mRNA expression level of LIF in the combination therapy group was higher than that in the model group and the gel therapy group throughout the observation period (P < 0.05). Conclusions: HA gel was effective in preventing the IUA adhesion formation at the early stage of the observation period, while ASC enhanced this effect throughout the observation period. Gel and ASC composites helped to improve endometrial receptivity.

Keywords

• Adipose-derived mesenchymal-stem cells
• Autocross-linked hyaluronic acid
• Endometrial receptivity
• Intrauterine adhesions
• Regeneration