Expression of sirtuins 1 in placenta, umbilical cord, and maternal serum of patients diagnosed with placenta accreta spectrum.

OBJECTIVE: Placenta accreta spectrum (PAS) is defined as the attachment of the placenta to the uterine wall in varying degrees. However, the studies have explored that the underlying molecular mechanisms of the PAS are very limited. Sirtuins 1 (SIRT1) is associated with placental development by controlling trophoblast cell invasion and remodeling of spiral arteries. We aimed to determine the expression level of SIRT1 in placentas, and maternal and umbilical cord serum of patients with PAS. METHODS: In total, 30 individuals in control, 20 patients in the placenta previa group, and 30 patients in the PAS group were included in this study. The expression levels of SIRT1 in the placentas were determined by Western blot and immunohistochemistry. Serum levels of SIRT1 in maternal and umbilical cord blood were determined by ELISA. RESULTS: SIRT1 was significantly lower in placentas of the PAS. However, maternal and umbilical cord serum samples were not significantly different between groups. CONCLUSION: SIRT1 may play an important role in the pathogenesis of the PAS.

Magnetic resonance imaging diagnosis of abnormal placental cord insertions.

INTRODUCTION: Abnormal placental cord insertions (APCIs) are significant risk factors for pregnancy complications, encompassing marginal cord insertion (MCI), velamentous cord insertion (VCI), and vasa previa (VP). While ultrasound is the primary imaging modality, its accuracy can be limited by factors such as maternal obesity and fetal positioning. Complementary to ultrasound, magnetic resonance imaging (MRI) offers a more precise visualization of the fetus, placenta, and umbilical cord relationships. This study aims to investigate the diagnostic value of prenatal magnetic resonance imaging (MRI) for APCIs compared with prenatal ultrasound. METHODS: We retrospectively collected data from 613 patients who underwent prenatal placental ultrasound and MRI. Of those who were confirmed as APCIs through surgery or pathology, the prenatal MRI features were compared with prenatal ultrasound. The diagnostic efficacy of prenatal MRI and ultrasound for APCIs was assessed based on the clinicopathological findings. RESULTS: Fifty-six patients were confirmed as APCIs by surgery or pathology, comprising 31 marginal cord insertions (MCIs), 18 velamentous cord insertions (VCIs), 5 vasa previa (VP) cases, and 2 VCI cases combined with VP. Ultrasound examination showed 55.36 % sensitivity (31/56) and 98.38 % specificity (486/494) in diagnosing APCIs, whereas MRI demonstrated 87.50 % sensitivity (49/56) and 98.88 % specificity (531/537). CONCLUSION: For APCIs complicated by placental location or morphological abnormalities, MRI demonstrates superior diagnostic efficacy compared to ultrasound in late pregnancy.

Fetal movement during delivery can lead to damage to the umbilical vessels and endanger the life of the fetus.

INTRODUCTION: Fetal umbilical cord hematoma has a low incidence but high mortality, and its cause during delivery is often unclear. We report an autopsy case in which it was concluded that umbilical cord hematoma resulted from fetal movements during childbirth. CASE PRESENTATION AND AUTOPSY FINDINGS: A 27-year-old primigravida at 39 + 2 weeks gestation with normal antenatal visits suffered a fetal heart rate decrease during active labor. Bedside ultrasound revealed fetal death in utero 22 min later. Forensic pathologists found that the umbilical vessels were torn and bleeding on almost the same plane, and the hematoma compressed both umbilical arteries, which is the cause of fetal stillness in utero. A total of 32 cases were reported, including 6 umbilical cord ruptures and 26 umbilical cord hematomas. The cause of hematoma was unknown in 77 % of cases, while dysplasia was present in 56.25 % of umbilical cords. DISCUSSION: This case indicates that fetal movements may cause umbilical cord vessel injury, particularly when oxytocin is used to induce labor. When fetal heart sounds decrease for no apparent reason, the possibility of cord injury should be considered, and cesarean delivery should be performed as soon as possible. Therefore, rigorous fetal heart tracing during active delivery is necessary.

Persistent omphalomesenteric duct in an infant with trisomy 21.

We present the case of a term newborn with trisomy 21 who presented to the paediatric emergency department with periumbilical flare and green-brown discharge from a clamped umbilical cord, initially suspected to be omphalitis. However, it was noticed later, that when the infant strained or cried, a thick, bubbling and offensive green-brown discharge came out of the clamped umbilical cord with umbilical flatus. An ultrasound abdomen and umbilical cord confirmed the presence of a persistent omphalomesenteric duct (POMD). He was then transferred to the paediatric surgical unit. There, he underwent a laparotomy and surgical resection of the POMD and was discharged home 2 days later.

Comparative study of difference in anatomy & histopathology of placenta & umbilical cord in natural pregnancy vs. IVF pregnancy & it's impact on fetal & maternal outcome.

AIM AND OBJECTIVES: Comparison of naturally conceived pregnancy with IVFET pregnancy for feto-maternal outcome and morphology and histopathology of placenta & umbilical cord. METHODS: 100 pregnant women were divided into 2 subsets of spontaneous pregnancy group (n = 50) and the IVFET pregnancy group (n = 50).The two groups were compared for Maternal age, parity, maternal weight gain, prepregnancy maternal BMI, gestational age, birth weight of baby, placental weight, placenta and umbilical cord cross sections, insertion site of the umbilical cord, and length of the umbilical cord. INCLUSION CRITERIA: Patients registered at ANC OPD/ART centre of our institute and subsequently reporting to maternity ward/ labor room for delivery at our centre. EXCLUSION CRITERIA: The pregnancies conceived after ART outside our institute, multifetal pregnancies. Study duration: 01 year Results: Our study revealed that spontaneous pregnancy group had less antenatal co-morbidities with more number of term vaginal deliveries and less intrapartum and neonatal complications compared to IVFET pregnancy women (p < 0.05). CONCLUSIONS: Assisted reproductive technologies have an impact on placental growth and function in pregnancy. The occurrence of placental abnormalities were the most significant and pertinent finding in the IVF-ET placentas. On histopathological examination maternal vascular malperfusion and concomitant anomalies of the umbilical cord were most noticeable findings.

A sustained decrease in the systolic/diastolic ratio may be a sign of severe adverse events in the umbilical cord: a report of eight cases.

A high systolic/diastolic (S/D) ratio of umbilical cord blood is a manifestation of intrauterine hypoxia. However, the clinical significance of a persistently decreased S/D ratio of umbilical cord blood has not been reported. We report eight cases of a persistently decreased S/D ratio of umbilical cord blood, with two cases of umbilical thrombus, five cases of excessive torsion, and one case of a true cord knot. Fetuses with a persistently decreased S/D ratio of umbilical cord blood may be at risk, and it may be an important indication of umbilical cord lesions.

Distribution of cord inflammation in cases with clinical suspicion of chorioamnionitis.

INTRODUCTION: Identification of acute funisitis, a sign of foetal inflammatory response (FIR), is crucial as their presence is associated with ominous neonatal outcomes. Recommendation on which part of umbilical cord should be sampled to facilitate optimal identification of acute funisitis is limited. METHODS: This is a retrospective cross-sectional study over a seven-month duration recruiting all patients with clinical suspicion of chorioamnionitis and/or maternal intrapartum pyrexia. The distribution and the degree of cord inflammation were assessed. The cases were also evaluated for maternal inflammatory response (MIR) and chorionic vasculitis (CV). RESULTS: Of the 191 placentas, 88 (46.1%) had some degree of cord inflammation. Forty-nine (55.7%) had a differential in cord inflammation, with distal cord section (n = 38) demonstrating significant greater inflammation than that of proximal cord section (n = 11) (p<0.001). There were 20 cases with phlebitis only and 8 cases demonstrated arteritis only in either proximal or distal cord sections. Increasing magnitude of cord inflammation was significantly associated with increasing severity of MIR and the rate of CV (p<0.001). CV was observed in 25 (24.3%) cases showing absence of cord inflammation, while 12 (13.6%) cases with cord FIR demonstrated no CV. DISCUSSION: Inflammatory reaction can occur variably throughout the length of the umbilical cord and chorionic plate vessels, with greater inflammation seen in the distal cord section. We affirm the current Amsterdam recommendation of submitting at least two cross sections of the cord representing proximal and distal sites and two sections from placental parenchyma to facilitate the identification of FIR.

Novel therapeutic targets, including IGFBP3, of umbilical cord mesenchymal stem-cell-conditioned medium in intrauterine adhesion.

Mesenchymal stem cells play important roles in repairing injured endometrium. However, the molecular targets and potential mechanism of the endometrial recipient cells for stem cell therapy in intrauterine adhesion (IUA) are poorly understood. In this study, umbilical cord mesenchymal stem-cell-conditioned medium (UCMSCs-CM) produced positive effects on a Transforming growth factor beta (TGF-ß) induced IUA cell model. RNA-sequencing was performed on clinical IUA tissues, and the top 40 upregulated and top 20 downregulated mRNAs were selected and verified using high-throughput (HT) qPCR in both tissues and cell models. Based on a bioinformatic analysis of RNA-sequencing and HT-qPCR results, 11 mRNAs were uncovered to be the intervention targets of UCMSCs-CM on IUA endometrium cell models. Among them, IGFBP3 was striking as a key pathogenic gene and a potential diagnostic marker of IUA, which exhibited the area under the curve (AUC), sensitivity, specificity were 0.924, 93.1% and 80.6%, respectively in 60 endometrial tissues. The silencing of IGFBP3 exerted positive effects on the IUA cell model through partially upregulating MMP1 and KLF2. In conclusion, RNA-sequencing combined with HT qPCR based on clinical tissues and IUA cell models were used in IUA research and our results may provide some scientific ideas for the diagnosis and treatment of IUA.

Single Umbilical Artery Umbilical Cord Is Associated With High-Grade Distal Fetal Vascular Malperfusion.

PURPOSE AND CONTEXT: Umbilical cord abnormalities with clinical signs of cord compromise are frequently associated with fetal vascular malperfusion (FVM). Single umbilical artery (SUA) has been reported to be associated with high-grade FVM in fetal growth restriction but not in an unselected population; our study aimed to address this issue. METHODS: Clinical and placental phenotypes of 55 consecutive placentas with SUA (Group 1) were compared with those of 655 placentas with 3-vessel umbilical cord (Group 2) from patients who were in the second half of their pregnancy. The placentas were histologically examined using hematoxylin and eosin (H&E) staining and CD 34 immunostaining. KEY RESULTS: Several umbilical cord phenotypes and high-grade distal FVM, based on H&E staining and endothelial fragmentation by CD34 were significantly more common in Group 1, whereas decidual clusters of multinucleate trophoblasts were more common in Group 2. Notably, H&E staining or CD34 immunostaining evaluated separately showed that high-grade distal FVM was more common in Group 1 than in Group 2, but the difference was not statistically significant. CONCLUSIONS: SUA predisposes to remote, advanced, and recent high-grade distal villous FVM, with a pathogenesis partly different from that of stasis-induced FVM, likely related to fetal anomalies associated with SUA.

Anticancer effect of hUC-MSC-derived exosome-mediated delivery of PMO-miR-146b-5p in colorectal cancer.

Antisense oligonucleotide (ASO) is a novel therapeutic platform for targeted cancer therapy. Previously, we have demonstrated that miR-146b-5p plays an important role in colorectal cancer progression. However, a safe and effective strategy for delivery of an ASO to its targeted RNA remains as a major hurdle in translational advances. Human umbilical cord mesenchymal cell (hUC-MSC)-derived exosomes were used as vehicles to deliver an anti-miR-146b-5p ASO (PMO-146b). PMO-146b was assembled onto the surface of exosomes (e) through covalent conjugation to an anchor peptide CP05 (P) that recognized an exosomal surface marker, CD63, forming a complex named ePPMO-146b. After ePPMO-146b treatment, cell proliferation, uptake ability, and migration assays were performed, and epithelial-mesenchymal transition progression was evaluated in vitro. A mouse xenograft model was used to determine the antitumor effect and distribution of ePPMO-146b in vivo. ePPMO-146b was taken up by SW620 cells and effectively inhibited cell proliferation and migration. The conjugate also exerted antitumor efficacy in a xenograft mouse model of colon cancer by systematic administration, where PPMO-146b was enriched in tumor tissue. Our study highlights the potential of hUC-MSC-derived exosomes anchored with PPMO-146b as a novel safe and effective approach for PMO backboned ASO delivery.

The Effects of Umbilical Cord Mesenchymal Stem Cells -Derived Exosomes in Oral Squamous Cell Carcinoma (In vitro Study).

OBJECTIVE: Mesenchymal stem cells (MSCs) derived exosomes offers several advantages as a cell-free therapeutic agents. In this study, Umbilical cord mesenchymal stem cells exosomes (UC-MSCs-exos) effects on oral squamous cell carcinoma (OSCC) cell line was evaluated. METHODS: UC-MSCs-exos were isolated and co-cultured with OSCC cells and their impact on OSCC was explored by various tests. Comet assay and western blot for cleaved caspase-3 and immunocytochemistry for caspase-8 were used for apoptosis assessment. HO-1 and Nrf2 were used to determine antioxidant levels. Tumor necrosis factor-α and interleukin-6 were assessed as inflammatory biomarkers. HOX transcript antisense intergenic long noncoding RNA (HOTAIR) expression was also evaluated. RESULTS: In a dose-dependent manner, UC-MSCs-exos reduced the levels of pro-inflammatory cytokines (IL-6 and TNF-α) and induced apoptosis of OSCC in vitro. Meanwhile, we found that UC-MSCs-exos downregulate HOTAIR. CONCLUSION: UC-MSCs-exos conferred a suppressive role on OSCC in vitro, highlighting a promising therapeutic role. However, the exact potentially involved molecules and molecular mechanisms need to be investigated in further studies.

Evaluation of preclinical efficacy of human umbilical cord mesenchymal stem cells in ankylosing spondylitis.

Objective: Umbilical cord mesenchymal stem cells (UCMSCs) have significant regenerative, tissue repair, and immunomodulatory properties that can help reduce inflammatory responses in patients with ankylosing spondylitis (AS). In this study, we used a combination of bovine proteoglycan and dimethyldioctadecylammonium (DDA) to establish a mouse model of proteoglycan-induced spondylitis (PGISp). To evaluate the therapeutic effects of UCMSCs, we treated PGISp mice with different doses of hUCMSCs via tail vein injection. Methods: At week 13, the PGISp mice exhibited thickened, erythematous paws, erythema in the extremities, and lameness. CT scans revealed necrotic lysis of chondrocytes, formation of fissures, visible hemorrhage, connective tissue hyperplasia, and focal infiltration of lymphocytes in the intervertebral discs. At week 14, the PGISp mice were randomly divided into three groups and administered different doses of hUCMSCs (0.25, 0.5, and 1.0×107 cells/kg, iv, QOW×2, n=10). To assess the therapeutic effects of hUCMSCs, we evaluated Th cell subsets in the spleen, spleen and thymus coefficients, peripheral blood inflammatory factors, and pathological and imaging observations of the spines and lumbar spines in the PGISp mice. Results: The results demonstrated that injection of hUCMSCs shifted the balance axis between Th1 and Th2 cells in the spleen towards Th2 cells. Moreover, the spleen coefficient and levels of inflammatory cytokines (TNF-α and CCL-2) in the serum decreased after hUCMSC injection. CT imaging and pathological analysis indicated that hUCMSC treatment inhibited ectopic osteogenesis and maintained clear small joint gaps, which slowed down the progression of structural lesions in the disc, nucleus pulposus, fibrous ring, and cartilage in PGISp mice. Conclusion: Administering hUCMSCs at the 14th week after modeling proved to be an effective treatment for PGISp mice. This experiment offers a valuable reference for the pre-clinical use of hUCMSCs in the treatment of AS.

Application of Human Umbilical Cord Mesenchymal Stem Cells in Rat Spinal Cord Injury Model.

The treatment of spinal cord injury (SCI) is a hot topic in clinic. In this study, female rats were selected and randomly divided into four groups (normal, sham, SCI, and mesenchymal stem cells [MSCs] groups). Hemostatic forceps were used to clamp the spinal cord for 1 min to establish the SCI animal model in rats. The levels of proinflammatory factors in the blood of each group were compared 4 h after operation. The motor function of hind limb was estimated by Basso, Beattie & Bresnahan Locomotor rating scale (BBB scale) at 3 months after surgery, the spinal cord tissue from the experimental area was obtained and stained histologically and immunohistochemically. Basso, Beattie & Bresnahan Locomotor rating scale results indicated that human umbilical cord (HUC) MSCs transplantation could improve the walking ability in rats with the SCI. Human umbilical cord mesenchymal stem cells substantially upregulated the secretion of anti-inflammatory factors and downregulated the secretion of proinflammatory factors, and promoted the repair of the SCI and inhibited the increase of glial cells induced by the SCI. Human umbilical cord mesenchymal stem cells transplantation can partially recovered the motor ability of rats with the SCI through promoting the regeneration of nerve cell and the expression of neural related genes, and inhibiting inflammatory reaction.

Cryopreserved human umbilical cord as a meningeal patch during in utero spina bifida repair in a modified ovine model.

OBJECTIVE: Despite in utero spina bifida (SB) repair, more than two-thirds of patients with SB are unable to ambulate independently, and 1 in 4 children need surgery for tethered cord by school age. The objective of this study was to test the cryopreserved human umbilical cord (HUC) as an antiscarring material to reduce tethering and improve function in a modified in utero SB repair model. METHODS: An SB defect (L2-6 levels) without myelotomy was created in fetuses of timed-pregnant ewes at gestational day (GD) 75. On GD 96, the fetal defect was exposed, and the arachnoid layer was removed to disrupt the barrier and expose the spinal cord to simulate human in utero SB repair. The fetuses were randomly assigned to two groups according to the method used to cover the spinal cord: the conventional repair (CR) group, for which myofascial closure was used (n = 7), and the HUC meningeal patch group, for which HUC was used as a meningeal patch (n = 6), followed by primary skin closure. The lambs were delivered at GD 140. Blinded clinical assessment of spinal cord function was performed using the Texas Spinal Cord Injury Scale (TSCIS). Histology of the spine was performed for quantitative assessment of spinal cord tethering, inflammatory markers, and arachnoid layer regeneration. RESULTS: The TSCIS scores were significantly lower in the CR than the HUC meningeal patch group (p = 0.0015) and the controls (p = 0.0018). The loss of spinal cord function in the CR group was mainly due to ataxia and loss of proprioception (p = 0.01 and 0.005 vs control and HUC, respectively). The histology at the repair site showed higher rates of spinal cord tethering in the CR lambs than the HUC lambs at all levels of the repair site (p = 0.01 and 0.02 vs control and HUC, respectively). In the CR with tethering compared with the HUC repair, there was a lower arachnoid layer covering at the repair site (p = 0.001). There was greater astrocyte activation in the posterior column in the CR than in the HUC repair group (p = 0.01). CONCLUSIONS: In a modified ovine SB model, the HUC as a meningeal patch allows regeneration of the arachnoid layer, prevents spinal cord tethering, and improves spinal cord function after in utero SB repair.

Peripheral cord insertion is associated with adverse pregnancy outcome only when accompanied by clinically significant placental pathology.

OBJECTIVE: To examine the relationship between umbilical cord insertion site, placental pathology and adverse pregnancy outcome in a cohort of normal and complicated pregnancies. METHODS: Sonographic measurement of the cord insertion and detailed placental pathology were performed in 309 participants. Associations between cord insertion site, placental pathology and adverse pregnancy outcome (pre-eclampsia, preterm birth, small-for-gestational age) were examined. RESULTS: A total of 93 (30%) participants were identified by pathological examination to have a peripheral cord insertion site. Only 41 of the 93 (44%) peripheral cords were detected by prenatal ultrasound. Peripherally inserted cords were associated significantly (P < 0.0001) with diagnostic placental pathology (most commonly with maternal vascular malperfusion (MVM)); of which 85% had an adverse pregnancy outcome. In cases of isolated peripheral cords, without placental pathology, the incidence of adverse outcome was not statistically different when compared to those with central cord insertion and no placental pathology (31% vs 18%; P = 0.3). A peripheral cord with an abnormal umbilical artery (UA) pulsatility index (PI) corresponded to an adverse outcome in 96% of cases compared to 29% when the UA-PI was normal. CONCLUSIONS: This study demonstrates that peripheral cord insertion is often part of the spectrum of findings of MVM disease and is associated with adverse pregnancy outcome. However, adverse outcome was uncommon when there was an isolated peripheral cord insertion and no placental pathology. Therefore, additional sonographic and biochemical features of MVM should be sought when a peripheral cord is observed. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Umbilical Cord Wharton's Jelly-Derived Mesenchymal Stem Cells Inhibit the TGF-ß1 Pathway in Hepatic Fibrosis Rats Through a Paracrine Regulation Process.

BACKGROUND: The aim is to verify the therapeutic effect and possible mechanism of human umbilical cord Wharton's jelly-derived transplantation of mesenchymal stem cells (UMSCs) on CCl4-induced hepatic fibrosis rats through in vivo studies and to explore the regulatory mechanism of UMSCs on fibrosis of hepatic stellate cells (HSCs) through in vitro experiments. METHODS: In vivo experiment: Rats were randomly divided into blank control group and hepatic fibrosis group. During the entire trial, the blank control group received subcutaneous injection of normal saline, while in the hepatic fibrosis group received injections of 50% CCl4-olive oil subcutaneously for 10 weeks to establish the rat model of liver fibrosis. Hepatic fibrosis rats were then randomly and evenly divided into umbilical cord mesenchymal stem cell (UMSC) group, bone marrow mesenchymal stem cell (BMSC) group, UMSC-culture medium (CM) group, and control group. Rats in each group were infused with the following substances through the caudal vein as follows: 1 mL UMSCs (2 × 106/mL) in UMSC group, 1 mL BMSCs (2 × 106/mL) in BMSC group, 1 mL UMSCs-CM in CM group, and 1 mL saline in control group. Rats of each group were closely observed (weight, hair condition, activity, appetite, diarrhea, etc.), venous blood samples were collected, the number of white blood cells and lymphocytes were measured, and liver function indicators (ALT, AST, TBIL, ALB) were determined. Three weeks later, rat liver specimens were taken, HE stained, pathological changes were examined and quantified. In vitro experiments: HSCs were seeded in 6-well plates at 1.0 × 105/mL, with a serum-free medium for 24 hours. Then, 2 mL of UMSCs-CM was added in the study group, while an equal amount of complete medium was added to the control group. RT-PCR was used to detect TGF-ß1, Collagen-I, TIMP-2 mRNA expression in HSCs, and western blot was used to detect TGF-ß1 protein expression in HSCs. RESULTS: In vivo experiment: Compared with the control group, after the transplantation, the activity status (weight, spirit, appetite, movement, hair, diarrhea, etc.) of rats in the UMSC group, BMSC group, and CM group were improved. The liver function indexes of these groups, such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were significantly decreased (p < 0.05), while albumin (ALB) levels were mildly but not significantly increased (p > 0.05). The Knodell score (reflecting the degree of liver inflammation) and Chevallier score (reflecting the degree of liver fibrosis) of liver specimens in pathological examination were also significantly reduced, and the difference in the quantitative scores of those indexes was statistically significant (p < 0.05). There was no statistically significant difference in the number of venous white blood cells and lymphocytes, liver function indexes (ALT, AST, TBIL, ALB), Knodell score, and Chevallier score of liver samples among the UMSC group, BMSC group, and CM group. In vitro experiments: After treatment with UMSCs-CM, the expression of TGF-ß1, Collagen-I, and TIMP-2 mRNA in HSCs was significantly down-regulated compared with that of the control group (treated with complete medium), and it gradually decreased with the extension of the treatment time. Compared with the control group, the expression of TGF-ß1 protein in the HSCs of the experimental group was down-regulated, and this effect was time-dependent, specifically, the control group (2.49 ± 0.43) > the experimental group at 48 hours (1.98 ± 0.26) > the experimental group at 72 hours (1.62 ± 0.20) (F = 7.796, p < 0.05). CONCLUSIONS: In rats with liver fibrosis, transplantation of UMSCs can improve liver function and reduce the inflammatory activity and fibrosis of the liver, possibly through the paracrine mechanism. UMSCs inhibit HSCs fibrosis through a paracrine mechanism, which is time-dependent, possibly by targeting TGF-ß1 and its downstream gene products.

The Effects of Umbilical Cord Mesenchymal Stem Cells on Traumatic Pancreatitis in Rats.

OBJECTIVE: This study explored the therapeutic and protective effects of umbilical cord mesenchymal stem cells (ucMSCs) on traumatic pancreatitis (TP) to provide a theoretical basis for TP treatment with MCSs by establishing a TP rat model. METHODS: We used 60 healthy adult male Sprague Dawley (SD) rats to create four experimental groups: sham, ucMSC control, TP, and ucMSC treatment. We observed ucMSC homing in the rats by fluorescence microscopy and assessed the degree of pancreatic tissue injury by hematoxylin and eosin (HE) staining on days 1, 3, and 7 after transplantation. Furthermore, we used an in vivo imaging system to evaluate the localization of cell membrane-stained ucMSCs in rats with TP. Finally, we measured the serum levels of amylase, lipase, pro-and anti-inflammatory factors, and oxidative stress factors by enzyme-linked immunosorbent assay (ELISA). RESULTS: The pancreatic histopathological score and the serum amylase and lipase levels were lower in the ucMSC treatment group than in the TP group (P < 0.05). Interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and oxidase malondialdehyde (MOD) levels were significantly higher in the ucMSC treatment group than in the TP group. However, IL-10, transforming growth factor-ß, and superoxide dismutase (an antioxidant enzyme, SOD) levels were significantly higher in the ucMSC treatment group than in the TP group (P < 0.05). CONCLUSION: ucMSCs can migrate and implant in injured areas of the pancreas in rats. Furthermore, they participate in pancreatic tissue repair and regulate immunity by inhibiting the systemic inflammatory response and oxidative stress.

[MicroRNA-204 Carried by Exosomes of Human Umbilical Cord-derived Mesenchymal Stem Cells Regulates the Polarization of Macrophages in a Mouse Model of Myocardial Ischemia-reperfusion Injury].

Objective To explore the role and mechanism of microRNA-204(miR-204) carried by the exosomes of human umbilical cord-derived mesenchymal stem cells(hUC-MSC) in regulating the polarization of macrophages in a mouse model of myocardial ischemia-reperfusion(I/R) injury. Methods After the hUC-MSCs were isolated,cultured,and identified,their adipogenic and osteogenic differentiation capabilities were determined.The exosomes of hUC-MSCs were separated by ultracentrifugation,and the expression of CD81,CD63,tumor susceptibility gene 101(Tsg101),and calnexin in the exosomes was determined by Nanoparticle Tracking Analysis software,transmission electron microscopy,and Western blotting.Three groups(hUC-MSC,miR-204 mimic,and negative control) were designed for the determination of the expression of miR-204 in the cells and their exosomes by qRT-PCR.The C57BL/6J mice were randomly assigned into a sham operation group,an I/R group,a hUC-MSC exosomes group,a negative control group,and a miR-204 mimic group.Except the sham operation group,the I/R model was established by ligating the left anterior descending artery.The echocardiography system was employed to detect the heart function of mice.HE staining was employed to observe the pathological changes of mouse myocardium.ELISA was employed to determine the levels of interleukin-1ß(IL-1ß),tumor necrosis factor-α(TNF-α),arginase 1(Arg-1),and IL-10 in the myocardial tissue.After the macrophages of mouse myocardial tissue were isolated,flow cytometry was employed to determine the expression of CD11c and CD206,and ELISA to measure the levels of IL-1ß,TNF-α,Arg-1,and IL-10 in the macrophages. Results hUC-MSCs had adipogenic and osteogenic differentiation capabilities,and the exosomes were successfully identified.Compared with the negative control group,the miR-204 mimic group showed up-regulated expression of miR-204 in hUC-MSCs and their exosomes(P<0.001,P<0.001).Compared with the sham operation group,the modeling of I/R increased the left ventricular end-diastolic diameter(LVEDD)(P<0.001),left ventricular end-systolic diameter(LVESD)(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P<0.001),and CD11c(P<0.001).Meanwhile,it lowered the left ventricular ejection fraction(LVEF)(P<0.001),left ventricular fractional shortening(LVFS)(P<0.001),Arg-1(P<0.001),IL-10(P<0.001),and CD206(P<0.001).Compared with those in the I/R group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P<0.001),and the levels of IL-1ß(P<0.001),TNF-α(P=0.010),and CD11c(P<0.001) reduced,while LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.028),and CD206(P=0.022) increased in the hUC-MSC exosomes group.Compared with those in the negative control group,the LVEDD(P<0.001),LVESD(P<0.001),myocardial injury score(P=0.001),and the levels of IL-1ß(P=0.048),TNF-α(P<0.001),and CD11c(P=0.007) reduced,while the LVEF(P<0.001),LVFS(P<0.001),and the levels of Arg-1(P<0.001),IL-10(P=0.001),and CD206(P=0.001) increased in the miR-204 mimic group. Conclusion The hUC-MSC exosomes overexpressing miR-204 can inhibit the polarization of macrophages in the I/R mouse model to M1-type and promote the polarization to M2-type.