BACKGROUND: Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have demonstrated efficacy in repairing uterine scars, although the underlying mechanisms remain unclear.
METHODS: Uterine injury was surgically induced in a rat model, followed by immediate transplantation of 5 × 10 ^ 5 hUC-MSCs to each side of the uterus. Uterine morphology was evaluated at days 14 and 30 using HE and Masson staining. Immunohistochemistry assessed macrophage polarization, angiogenesis and endometrial receptivity in the endometrium. Additionally, the regulatory effects of hUC-MSCs on macrophage polarization were explored through coculture. qRT-PCR quantified the expression of anti-inflammatory (IL10 and Arg1) and pro-inflammatory (iNOS and TNF-α) factors. Western blotting evaluated CD163 expression.
RESULTS: Transplantation of hUC-MSCs promoted the healing of uterine injuries and tissue regeneration while inhibiting tissue fibrosis. Immunohistochemistry at days 14 and 30 post-transplantation demonstrated the polarization of macrophages toward the M2 phenotype in the uterine injury area in the presence of hUC-MSCs. Furthermore, hUC-MSC transplantation improved angiogenesis and endometrial receptivity in the uterine injury rat model, associated with increased IL10 expression. hUC-MSC-induced angiogenesis can be resisted by depleted macrophages. In vitro coculture experiments further demonstrated that hUC-MSCs promoted IL10 expression in macrophages while suppressing TNF-α and iNOS expression. Western blotting showed enhanced CD163 expression in macrophages following hUC-MSC treatment.
CONCLUSIONS: hUC-MSCs contribute to the healing of uterine injuries by targeting macrophages to promote angiogenesis and the expression of anti-inflammatory factors.

Uterine scar was one of the long-term complications cesarean section. In this study, an thermo-responsive injectable hydrogel loaded with human umbilical cord mesenchymal stem cells (UCMSCs) and asiaticoside microspheres (AMs) was used for uterine scar repair, which was prepared by optimizing the mixed ratio of aldehyde-functionalized Pluronic F127 (F127-CHO) and adipic dihydrazide-modified hyaluronic acid (AHA). The asiaticoside was loaded in Poly (DL-lactide-co-gycolide) (PLGA) by emulsion- diffusion-evaporation method. The hydrogel had appropriate pore size, good mechanical property, and slow release ability of asiaticoside. In vitro cell experiments demonstrated that F127-CHO/AHA/AMs could effectively promote stem cell adhesion and proliferation, promote angiogenesis, and provide a suitable microenvironment for cell survival. The F127-CHO/AHA/AMs/UCMSCs hydrogel was further used to repair uterine scar in female SD rats. The results showed that the prepared hydrogel could promote the proliferation of rat endometrial cells, promote the regeneration of glands, reduce the degree of endometrial fibrosis and restore the morphology of uterine cavity. The hydrogel could upregulate expression of Ki67 and IGF-1, downregulate TGF-β1 expression and promote M1-M2 transition of macrophages. This study confirmed that the prepared hydrogel could be used as an effective transplantation strategy, which could be expected to achieve clinical transformation of uterine scar repair.

UNASSIGNED: To compare the maternal and neonatal outcomes of placenta previa (PP) with and without coverage of a uterine scar in Foshan, China.
UNASSIGNED: A retrospective cohort study comparing all singleton pregnancies with PP was conducted at a tertiary, university-affiliated medical center from 1 January 2012 to 31 April 2017 in Foshan, China. Demographic, clinical and laboratory data were extracted from electronic medical records (EMRs). Maternal and neonatal outcomes of PP with and without coverage of a uterine scar were compared by statistical method.
UNASSIGNED: There were 58,062 deliveries during the study period, of which 726 (1.25%) were complicated PP in singleton pregnancies and were further classified into two groups: the PP with coverage of a uterine scar group (PPCS, n=154) and the PP without coverage of a uterine scar group (Non-PPCS, n=572). Overall, premature birth (<37 weeks, 67.5% vs 54.8%; P=0.019), cesarean section (100% vs 97.6%; P=0.050), intraoperative blood loss >1000 mL (77.9% vs 16.0%; P<0.001) or >3000mL (29.9% vs 3.0%; P<0.001), bleeding within 2-24 hours after delivery (168.2±370.1 ml vs 49.9±58.4 ml; P<0.001), postpartum hemorrhage (48.7% vs 15.7%; P<0.001), transfusion (34.6% vs 16.1%; P<0.001), hemorrhage shock (7.8% vs 1.9%; P<0.001), hysterectomy (2.6% vs 0.5%; P=0.019), fetal distress (35.7% vs 12.1%; P<0.001) and APGAR score at 1 min (15.2% vs 7.1%; P=0.002) had a significant difference between PPCS group and Non-PPCS group. After grouping by whether complicated with placenta accreta spectrum disorders (PASD), we found that PPCS was significant associated with more intraoperative blood loss >1000mL, intraoperative blood loss >3000mL, bleeding within 2-24 hours after delivery and fetal distress than the Non-PPCS group.
UNASSIGNED: The PPCS group had poorer maternal and neonatal outcomes than the Non-PPCS group after grouping by whether pregnancies complicated with PASD or with different placental positions.

Cesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section. Serious CSD may eventually result in infertility or obstetrical complications. Human amniotic epithelial cells (hAECs) have shown great promise in tissue regeneration. This study aims to investigate whether hAEC transplantation has the therapeutic effects on the rat uterine scar following full-thickness injury.
A rat uterine scar model was established by excising the full-thickness uterine wall of about 1.0 cm in length and 1/2-2/3 of the total circumference in width. At day 30 post-surgery, hAECs were transplanted into the uterine scar. At day 30 and 60 post-transplantation, hematoxylin and eosin (H&E) staining, Masson staining, and IHC staining for vWF, VEGFA, α-SMA, and MMP-8 were performed to evaluate the regeneration of the scarred uterus and the underlying mechanism. Pregnancy outcomes were assessed at day 60 after hAEC transplantation. Finally, hAECs were incubated with hydrogen peroxide to verify the paracrine effect of hAECs.
Collagen deposition, thin myometrium, and injured endometrium were observed in the rat uterine scar model. After hAEC transplantation, collagen deposition in the uterine scar decreased, and myometrial and endometrial recovery was facilitated. hAEC transplantation also increased the fetus number implanted within the scarred area. Moreover, we found hAECs promoted angiogenesis via upregulation of VEGFA and decreased collagen deposition by upregulating MMP-8 in the uterine scar. The in vitro studies further demonstrated an increase in the expression level of MMP-8 in hAECs cultured with hydrogen peroxide.
These results suggested that hAEC transplantation may be efficacious in the functional repair and collagen degradation of uterine scars, which provides a new therapeutic strategy to CSD.

UNASSIGNED: Wound complications are a major source of morbidity after cesarean section (CS) and contribute to increased risks in subsequent pregnancies. In the present study, we aim to investigate the wound healing potential of a kind of oligopeptide compound, mainly derived from the marine fish peptides (MFPs), in rats after CS by biomechanical, biochemical, and histological methods.
UNASSIGNED: Eighty-four pregnant Sprague-Dawleyrats were randomly assigned to four groups, namely the control group and 1.1, 2.2, and 4.4 mg/kg MFP groups, respectively. The MFPs or normal saline of the equal volume was intragastrically administered every morning on the second day after CS. On days 5, 10, and 15 after the surgery, seven rats from each group were randomly selected. The samples of skin wound and uterus were harvested and then used for the following experiments and analyses.
UNASSIGNED: Using the CS rat model, this study demonstrated that in the MFP groups, the skin tensile strength, uterine bursting pressure, and hydroxyproline (Hyp) were significantly higher than those in the control group at all three time points (P < 0.05). The formation of collagen and smooth muscle fibers and the expression of CD34 and connective tissue growth factor at the incision site were increasingly observed in the MFP groups (P < 0.05).
UNASSIGNED: MFPs have a great potential to accelerate the process and quality of wound healing in rats after CS.