Human Umbilical Cord Mesenchymal Stem Cells Encapsulated with Pluronic F-127 Enhance the Regeneration and Angiogenesis of Thin Endometrium in Rat via Local IL-1β Stimulation

Abstract

Thin endometrium (< 7 mm) could cause low clinical pregnancy, reduced live birth, increased spontaneous abortion, and decreased birth weight. However, the treatments for thin endometrium have not been well developed. In this study, we aim to determine the role of Pluronic F-127 (PF-127) encapsulation of human umbilical cord mesenchymal stem cells (hUC-MSCs) in the regeneration of thin endometrium and its underlying mechanism. Thin endometrium rat model was created by infusion of 95% ethanol. Thin endometrium modeled rat uterus were treated with saline, hUC-MSCs, PF-127, or hUC-MSCs plus PF-127 separately. Regenerated rat uterus was measured for gene expression levels of angiogenesis factors and histological morphology. Angiogenesis capacity of interleukin-1 beta (IL-1β)-primed hUC-MSCs was monitored via quantitative polymerase chain reaction (q-PCR), Luminex assay, and tube formation assay. Decreased endometrium thickness and gland number and increased inflammatory factor IL-1β were achieved in the thin endometrium rat model. Embedding of hUC-MSCs with PF-127 could prolong the hUC-MSCs retaining, which could further enhance endometrium thickness and gland number in the thin endometrium rat model via increasing angiogenesis capacity. Conditional medium derived from IL-1β-primed hUC-MSCs increased the concentration of angiogenesis factors (basic fibroblast growth factor (bFGF), vascular endothelial growth factors (VEGF), and hepatocyte growth factor (HGF)). Improvement in the thickness, number of glands, and newly generated blood vessels could be achieved by uterus endometrium treatment with PF-127 and hUC-MSCs transplantation. Local IL-1β stimulation-primed hUC-MSCs promoted the release of angiogenesis factors and may play a vital role on thin endometrium regeneration.

Impaired receptivity of thin endometrium: therapeutic potential of mesenchymal stem cells

“…Multiple studies have tested novel matrix delivery systems for MSCs isolated from human pregnancy tissues (e.g. umbilical cord, placenta, amnion) (134)(135)(136)(137)(138), given their low immunogenicity and ease in collection at delivery. Lin et al evaluated MSCs isolated from human placenta (HP-MSC) encapsulated in hyaluronic acid (HA) hydrogel for intrauterine delivery in a mouse model of endometrial injury (134).…”

Mesenchymal Stem Cells in Soft Tissue Regenerative Medicine: A Comprehensive Review

“…Furthermore, Zhou et al (2022) described that Pluronic F-127-encapsulated human UC-MSCs can restore the morphology of thin endometrium in a rat model with increased endometrium thickness and gland number and stimulated neovascularization. Moreover, IL-1β-primed human UC-MSC-derived conditioned media enhanced the concentration of vital angiogenesis factors bFGF, VEGF, and HGH [ 112 ]. Another report also explained that UC-MSCs migrate to the injured endometrium and promote the recovery of the thin endometrium and its structure and function [ 113 ].…”

Human Umbilical Cord-Based Therapeutics: Stem Cells and Blood Derivatives for Female Reproductive Medicine

“…However, this treatment was unable to restore fertility. On the other hand, Zhou et al [219] encapsulated the hUC-MSCs in a synthetic thermosensible hydrogel (Pluronic F-127), which was injected into rats in the right side of uterine horns nine days after they modeled a thin endometrium. This bioengineering strategy enlarged the endometrium and restored its cell proliferation and angiogenesis.…”