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Treatment of digital nerve injuries, particularly in case of a gap, is challenging. Recovery of finger sensitivity is often incomplete and can impair personal and occupational activity. The need for better nerve regeneration has given rise to alternative treatments such as nerve conduits. This study aimed to evaluate the safety and efficacy of a conduit of freeze-dried inverted human umbilical cord vessel for regeneration in digital nerve section. Twenty-three patients with a mean nerve gap of 6.11 mm (range 2-30 mm and static 2-point discrimination (s2PD) 15 mm underwent surgical repair of digital nerve section using a nerve regeneration conduit. The primary endpoint was recovery of sensitivity after conduit implantation. Secondary endpoints comprised progression of pain, functional symptoms, pressure threshold, hand-specific symptoms and disabilities, and restored innervation. Mean follow-up was 10.1 ± 4.1 months (range 1-14 months). Sensitivity recovered progressively in the months following implantation. There was a mean decrease of 8.54 mm in s2PD between baseline and last follow-up (p 0.001). Complete innervation recovered in 83.3% of cases at last follow-up. Pressure threshold and hand-related quality of life improved significantly and symptoms due to nerve sectioning (pain, cold intolerance, hypoesthesia, hyperesthesia) resolved almost completely. There were no safety issues related to the nerve conduit. These results indicate that freeze-dried inverted human umbilical vessels can be a safe and effective option as conduit for digital nerve regeneration.

This study evaluated the potential of Wharton's jelly mesenchymal stem cells with high tolerogenic properties in reducing immunosuppressive dosage and related adverse effects.A 4- to 6-week-old, 30-40 g weight, male inbred CD57BL/6 mice were used as skin allograft donors, whereas Balb/c mice with similar characteristics were used as recipients. Wharton's jelly stem cells were obtained from a commercial kit sourced from human umbilical cord. Skin allografts were performed from CD57Bl6 to Balb/c mice (day 0). Group 1 (control) received no treatment. Group 2 received 15 mg/kg cyclosporin A on days 0 to 30. Group 3 received 5.7 × 10 6 and 10.3 × 10 6 cell/kg Wharton's jelly stem cells on days 0 and 3, respectively. Groups 4, 5, and 6 received a combination of 15, 10, and 5 mg/kg per day cyclosporine A (days 0 to 30) with the same stem cell dose with group 3, respectively. Graft rejection was evaluated with digital photography and thermal imaging, histopathology (Banff grading, epithelialization scores, dermoepidermal dissociation), immunochemistry (Ki-67 and Bcl-2), and biochemical methods (interleukin 10, interleukin 2, interferon γ, tumor necrosis factor α) (day 10). Cumulative adverse effects of cyclosporin A occurring in the groups were revealed by histopathological evaluation of kidney and liver (a modified semiquantitative method of infiltration of inflammatory cells around the portal area and lobular region in liver; modification of the Banff rating of proximal tubules and hypertrophia of juxtaglomerular apparatus cells in kidney) (day 30).There was no rejection in groups 2, 4, and 5 until the end of study. These were statistically different versus groups 1 (day 10 ± 0.71), 3 (day 11 ± 0.82), and 6 (day 11 ± 0.58) (all P 's0.05). Groups 4 and 5 have exhibited statistically similar findings in histopathological (4 epithelization score: 3.7 ± 1.3; 5 epithelization score: 3.5 ± 0.5; 4 Banff grading score: 0.8 ± 0.6; 5 Banff grading score: 1.0 ± 0.5; both P 's = 1.00), immunohistochemical (4 Bcl-2 score: 3.5 ± 0.5, P = 0.618; 5 Bcl-2 score: 3.4 ± 0.5, P = 1.00; 4 Ki-67 score: 3.7 ± 0.4, P = 1.00; 5 Ki-67 score: 3.5 ± 0.5, both P 's = 1.00), and levels of cytokines (both P 's = 1.00) versus group 2. Adverse effects on kidneys and liver were lowest and statistically similar in groups 3, 5, and 6 (all P 's = 00) versus group 1.Wharton's jelly mesenchymal stem cells alter bioavailability of cyclosporine, albeit at much lower doses and with fewer systemic adverse effects.

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as

The purpose of this study was to determine the association between the postnatal umbilical coiling index (pUCI) and vascular endothelial growth factor A (VEGFA) and its receptor (VEGFR2) in parturients with and without gestational diabetes mellitus (GDM).Within 24 h following birth, the umbilical cord and pUCI of 29 newborns with GDM and 28 neonates with non-GDM parturients were prospectively examined. Real-time PCR tests were used to determine the expression levels of the VEGFA and VEGFR2 genes, measured from the umbilical cord. The Mann-Whitney and Chi-squared tests were used to compare continuous and discrete variables with and without GDM.The median (IQR) of maternal age was 30 (26-34) years. There were no differences in demographic features between GDM and non-GDM parturients. While there was a marginal difference in VEGFA expression levels between the GDM and non-GDM groups (P-values = 0.07), no difference was detected for VEGFR2 (P-values = 0.75). Comparing hyper- and hypocoiling cords revealed a small difference in VEGFA levels (P-values = 0.05), but no change in VEGFR2 (P-values = 0.50). Furthermore, in both GDM and non-GDM parturients, down-regulated VEGFA was the general rule among abnormal pUCIs.The GDM and coiling state both are associated with the amount of VEGFA expression, but neither is related to VEGFR2. Furthermore, regardless of whether the patient has GDM or not, the abnormal coiling pattern appears to be related to the VEGFA down-regulation.

No approved effective therapy for non-alcoholic steatohepatitis (NASH) is currently available. Exosomes derived from mesenchymal stem cells (MSCs) perform the functions such as inhibiting inflammation, anti-oxidative stress, regulating immunity, but it is not clear whether human umbilical cord mesenchymal stem cells (hUC-MSCs) exosomes protect against NASH through Nrf2/NQO-1 pathway. Therefore, this study was conducted to investigate the effects of hUC-MSCs exosomes on NASH through Nrf2/NQO-1 pathway in vivo and in vitro.C57BL/6J male mice were fed with high fat and high cholesterol diet (HFHC) and methionine choline deficiency diet (MCD). Mice were treated with or without hUC-MSCs exosomes by tail intravenous injection. The liver histology, lipid metabolism and oxidative stress were evaluated. HepG2 and AML12 cells were incubated with palmitic acid (PA) and MCD conditioned medium, respectively. Then the therapeutic effect of hUC-MSCs exosomes in steatotic cells was evaluated. To elucidate the signaling pathways, the Nrf2-specific blocker ML385 was applied to intervene in vitro.In NASH models, hUC-MSCs exosomes attenuated steatosis in hepatocytes, altered the abnormal expression of lipid-related genes including SREBP-1c, PPAR-α, Fabp5, CPT1α, ACOX and FAS, suppressed the hepatic inflammatory responses by decreasing the expression of F4/80Nrf2/NQO-1 antioxidant signaling pathway may play a key role in the treatment of NASH by hUC-MSCs exosomes.

Umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. Little is known about the impact of umbilical cord milking on long-term neurodevelopmental outcomes. The objective of this study is to compare the effects of intact umbilical cord milking (UCM) vs. early cord clamping (ECC) at birth on neurodevelopmental outcomes at 36 months' corrected age. Preterm infants 31 weeks' gestation who were randomized at birth to receive three time milking of their attached cord or ECC ( 10 s) were evaluated at 36 months' corrected age. Neurodevelopmental outcomes were assessed by blinded examiners using Bayley Scales of Infant and Toddler Development (version III). Analysis was by intention to treat. Out of the 73 infants included in the original trial, 2 died and 65 (92%) infants were evaluated at 36 months' corrected age. Patient characteristics and short-term outcomes were similar in both study groups. There were no significant differences in the median cognitive, motor or language scores or in the rates of cerebral palsy, developmental impairment, deafness, or blindness between study groups.Neurodevelopmental outcomes at 36 months' corrected age of very preterm infants who received UCM were not shown to be significantly different from those who received ECC at birth.ClinicalTrials.gov: NCT01487187 What is Known: • Compared to early cord clamping, umbilical cord milking improves postnatal adaptation and short-term outcomes of very preterm infants compared to early cord clamping. • Little is known about the impact of umbilical cord milking on neurodevelopmental outcomes.• Neurodevelopmental outcomes at 3 years of age were not significantly different in very preterm infants who received cord milking vs. those who received early cord clamping at birth.

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.

Wharton's Jelly (WJ)-derived Mesenchymal Stromal Cells (MSC) are currently in the spotlight for the development of innovative MSC-based therapies due to their ease of sourcing, high proliferation capacity and improved immunopotency over MSC from other tissue sources. However, the short time window for derivation from donated fresh umbilical cord (UC) tissue fragments does not allow to consider biological features of the donor beyond serological safety testing. This limits the scope of MSC banking to rapid, prospective derivation of MSC, WJ lines without considering biological and genetic characteristics of the donor that may influence their suitability for clinical use (e.g. HLA type, inherited gene variants). In the present study, we describe a simple, efficient and reproducible approach for the cryopreservation of UC tissue fragments, compatible with established workflows in existing public frameworks for cord blood and tissue collection while guaranteeing pharmaceutical grade of starting materials for further processing under GMP standards. Herein we demonstrated the feasibility of time and cost-saving methods for cryopreservation of unprocessed UC tissue fragments directly at reception of the donated tissues using 10% Me

The main challenges in clinical applications of mesenchymal stem cells (MSCs) are attributed to their heterogeneity. It is believed that preconditioning of MSCs with active compounds may enhance the expression of potentially therapeutic molecules and thus achieve stable and effective therapeutic outcomes. In the present study, we investigated the mechanism by which pyrogallol increased the therapeutic efficacy of human umbilical cord mesenchymal stem cells (hUCMSCs) against LPS-induced acute lung injury (ALI). hUCMSCs with pyrogallol treatment increased expression of HO-1 at both mRNA and protein levels, accompanied by Kelch-Like ECH-Associated Protein 1 (Keap1) degradation, and upregulation of the Nrf2 protein levels as well as nuclear translocation of Nrf2. Moreover, the modulation of Keap1 and Nrf2 as well as HO-1 upregulation by pyrogallol was reversed by pretreatment with N-acetylcysteine (NAC) and a P38 kinase inhibitor (SB203580). Whereas, NAC pretreatment abrogated pyrogallol-mediated activation of P38 kinase, indicating that pyrogallol-derived ROS led to P38 kinase activation, thus promoting Nrf2/HO-1 signaling. Additionally, we found that the induction of p62 by the pyrogallol-mediated ROS/P38/Nrf2 axis interacted with Keap1 and resulted in autophagic degradation of Keap1, which created a positive feedback loop to further release of Nrf2. Furthermore, the increased expression of HO-1 in pyrogallol-pretreated hUCMSCs led to enhanced inhibitory effects on LPS-mediated TLR4/P-P65 signaling in BEAS-2B cells, resulting in increasing suppression of LPS-indued expression of a series of pro-inflammatory mediators. Compared to untreated hUCMSCs, Sprague-Dawley (SD) rats with pyrogallol-primed hUCMSCs transplantation showed enhanced improvements in LPS-mediated lung pathological alterations, the increased lung index (lung/body ratio), apoptosis of epithelial cells, the activation of TLR4/NF-κB signaling as well as the release of pro-inflammatory mediators. Together, these results suggested that hUCMSCs with pyrogallol pretreatment enhanced the therapeutic efficacy of hUCMSCs, which may provide a promising therapeutic strategy to maximize the therapeutic efficacy of hUCMSC-based therapy for treating LPS-associated ALI.

Background: Anaemia in infants is a major public health concern particularly in low and middle-income countries. Delayed cord clamping (DCC) has been advocated as a strategy to decrease iron deficiency anaemia in infants because of the benefits that come with placental transfusion. Despite the documented benefits of delayed cord clamping in preventing anaemia the current practices of delayed cord clamping by midwives and obstetricians across countries and in different contexts is unclear. This narrative review assesses the literature on delayed cord clamping practices published from 2013 to February 2022, in order to examine current practice in birth units globally, and with a focus in low and middle-income countries (LMICs). Method: A search of four bibliographic databases Medline, Scopus (Elsevier), ProQuest, CINAHL and two network and search engines, Wiley and Google Scholar, was undertaken from 2013 to February 2022 using key terms related to delayed cord clamping and immediate cord clamping. A snowball method as well as backward and forward reference checking was also undertaken. Results: The search strategy identified 10 studies on umbilical cord clamping practices by midwives and obstetricians. Only two studies were conducted in low and middle-income countries. Conclusion: Despite the potential benefits of DCC in reducing anaemia, particularly in low and middle-income countries where the burden of anaemia is a public health concern, there is a paucity of literature on current DCC practices by obstetricians and midwives. Research to establish current DCC practices in these countries is needed to address this gap in the literature. Refereed/Peer-reviewed

Aim The objective of this study was to examine the effect of delayed umbilical cord clamping on the newborn's oxygen saturation and sucking success in primiparas. Methods The study was conducted based on the experimental model with a control group, between March 15-November 10, 2020. The sample of the study consisted of 101 primiparous pregnant (48 primiparous with delayed cord clamping within 1-3 min and 53 primiparous with early cord clamping within 1 min) (having no high-risk pregnancy, 38-42 weeks, vaginal birth) in Turkey. The data were collected using a personal information form, the LATCH breastfeeding tool and the pulse oximetry. Statistical analyses were conducted using percentage distribution, arithmetic means, chi-square testing, and independent samples t-testing. Results Oxygen saturation values of newborns with delayed umbilical cord clamping were higher than those of newborns with early cord clamping. The saturation was first minute 66.43 versus 74.37, fifth minute 81.90 versus 88.60, tenth minute 91.77 versus 94.50 (p < 0.05). When compared to the group with early cord clamping, oxygen saturation is higher in the first by 11.95%, in the fifth by 8.18%, and in the tenth minute by 2.97% in the group with delayed cord clamping. The LATCH breastfeeding scores were found to be higher in the group with delayed cord clamping compared to the group with early cord clamping. Conclusion It was determined that delayed cord clamping positively affected oxygen saturation values and sucking success in neonatal babies. Delayed umbilical cord clamping is an important issue that needs to be addressed in its different dimensions.

Human umbilical cord mesenchymal stem cells (HUMSCs) are one of the most attractive sources of stem cells, and it is meaningful to design and develop a type of microcarriers with suitable mechanical strength for HUMSCs proliferation in order to acquire enough cells for cell-based therapy. Alginate-gelatin core-shell (AG) soft microcarriers were thus fabricated via a microfluidic device with droplet shearing/gelation facilities and surface coating for in vitro expansion of HUMSCs. The attachment and proliferation of HUMSCs on AG microcarriers with different mechanical strengths modulated by gelatin coating was studied, and the harvested cells were characterized to verity their differentiation potential. The obtained core-shell microcarriers were all uniform in size with a high mono-dispersity (CV 5 %). An increase in the gelatin surface coating concentration from 0.5 % to 1.5 % would lead to the reduction in both the particle size of the microcarriers and swelling ratio upon the contact of culture medium, but increased elastic modulus. Microcarriers of 245.12 μm with a gelatin coating elastic modulus of 27.5 kPa (AG10) were found to be the optimal substrate for HUMSCs with an initial attachment efficiency of 44.41 % and a 5-day expansion efficiency of 647 %. The cells harvested from AG10 still reserved their outstanding pluripotency. Fresh AG10 could smoothly transfer cells from a running microcarrier-cell system of confluence to serve as a convenient way of scaling-up the existing culture. The current study thus developed suitable microcarriers, AG10, for in vitro HUMSCs expansion with well reserve of cell multipotency, and also provided a manufacturing and surface manipulating strategy of precise production and fine regulation of microcarrier properties.

BackgroundCOVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology.ObjectiveThis study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes.Study designThis was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings.ResultsThis study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy.ConclusionPlacentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Stromal cells possess unique properties to regenerate themselves and cure various chronic illnesses. An easily available and ethical source for procurement of stromal cells is umbilical cord blood which is now being stored for future use. Vedic texts also describe the cord blood as a source of life. However, Indian traditions seem to preserve one more alternative for storage and procurement of stromal cells. Traditionally, in many parts of India, the umbilical cord stump is dried and stored for future use. It is used as a medicine for some illness and to treat infertility. Since Indian traditions are an excerpt of Vedic science, it points towards the possible emergence of dried stump as an easy and cost-effective means for stromal cell procurement and storage. The present review compiles the literature available on these traditional practices and stresses upon the need of rigorous experimental and theoretical research in the area.

Objectives: Placental tissue is an established biomaterial used in many clinical applications. However, its use for tissue engineering purposes has not been fully realized. Though articular cartilage extracellular matrix (ECM)-derived oriented scaffolds for cartilage tissue engineering were developed, resources are a hindrance to its application. In this regard, the present study investigated the feasibility of using intact decellularized human umbilical cord Wharton’s jelly (hUC-WJ) as a new material for chondrocyte carrier in cartilage tissue engineering. The developed hUC-WJ scaffold provides a good microenvironment for the attachment, viability, and delivery of seeded human autologous chondrocytes. It has an advantage over other biomaterials in terms of abundant availability and similar biochemistry to cartilage ECM. Materials and methods: hUC-WJ obtained from fresh human placenta were decellularized and gamma sterilized. Human cartilage tissue was obtained from the patients with a total knee replacement. The chondrocytes were isolated and expanded in-vitro and seeded onto the hUC-WJ scaffold. The efficiency of the decellularized tissue as a delivery system for human cartilage cells was investigated by histology, immunohistochemistry, cell count, flow cytometry, and scanning electron microscopy (SEM). Results: The results showed that the decellularized hUC-WJ scaffold has supported the microenvironment for chondrocyte attachment and viability without losing its phenotype. In addition, the cells were spread through the hUC-WJ scaffold as confirmed by histology and SEM. Conclusion: Based on obtained results, the hUC-WJ scaffold has great potential as a 3D scaffold for human autologous chondrocyte carriers in tissue engineering and regenerative medicine applications.

Necrotizing funisitis is a distinct lesion of the umbilical cord associated with chorioamnionitis and bloodborne fetal infection. The lesion may be a response to microorganisms in Wharton's jelly. A common microorganism detected in chorioamnionitis is Ureaplasma urealyticum (U. urealyticum). This study hypothesizes that U. urealyticum DNA will be present in Wharton's jelly in necrotizing funisitis.Necrotizing funisitis was identified retrospectively from a 2-year pathology database and confirmed in review. Paraffin fixed embedded tissue sections of the lesion were prepared for polymerase chain reaction (PCR) by using primers to identify U. urealyticum. Twenty matched controls without funisitis were similarly processed. Clinical data included serological tests of common bloodborne infections in the mothers and infants, and U. urealyticum PCR results in the urine of the neonates.Fourteen cases of necrotizing funisitis were identified in 7,416 examined placentas. Nine of these umbilical cords were positive by PCR for U. urealyticum (64.3%). Nineteen of twenty control cases were negative. Eight of ten neonates (80%) also had positive urine PCR tests for U. urealyticum. No infants or mothers had evidence of bloodborne fetal infection.U. urealyticum DNA was present in Wharton's jelly by PCR testing in the majority of the necrotizing funisitis lesions tested. This result supports a possible causative role for U. urealyticum in many cases of necrotizing funisitis.

Background: Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) remains a serious clinical problem but has no approved pharmacotherapy. Mesenchymal stem cells (MSCs) represent an attractive therapeutic tool for tissue damage and inflammation owing to their unique immunomodulatory properties. The present study aims to explore the therapeutic effect and underlying mechanisms of human umbilical cord MSCs (UC-MSCs) in ALI mice. Objective: In this study, we identify a novel mechanism for human umbilical cord-derived MSCs (UC-MSCs)-mediated immunomodulation through PGE2-dependent reprogramming of host macrophages to promote their PD-L1 expression. Our study suggests that UC-MSCs or primed- UC-MSCs offer new therapeutic approaches for lung inflammatory diseases. Methods: Lipopolysaccharide (LPS)-induced ALI mice were injected with 5×105 UC-MSCs via the tail vein after 4 hours of LPS exposure. After 24 hours of UC-MSC administration, the total protein concentration and cell number in the bronchoalveolar lavage fluid (BALF) and cytokine levels in the lung tissue were measured. Lung pathological changes and macrophage infiltration after UCMSC treatment were analyzed. Moreover, in vitro co-culture experiments were performed to analyze cytokine levels of RAW264.7 cells and Jurkat T cells. Results: UC-MSC treatment significantly improved LPS-induced ALI, as indicated by decreased total protein exudation concentration and cell number in BALF and reduced pathological damage in ALI mice. UC-MSCs could inhibit pro-inflammatory cytokine levels (IL-1β, TNF-α, MCP-1, IL-2, and IFN-γ), while enhancing anti-inflammatory cytokine IL-10 expression, as well as reducing macrophage infiltration into the injured lung tissue. Importantly, UC-MSC administration increased programmed cell death protein ligand 1 (PD-L1) expression in the lung macrophages. Mechanistically, UC-MSCs upregulated cyclooxygenase-2 (COX2) expression and prostaglandin E2 (PGE2) secretion in response to LPS stimulation. UC-MSCs reduced the inflammatory cytokine levels in murine macrophage Raw264.7 through the COX2/PGE2 axis. Furthermore, UC-MSC- derived PGE2 enhanced PD-L1 expression in RAW264.7 cells, which in turn promoted programmed cell death protein 1 (PD-1) expression and reduced IL-2 and IFN-γ production in Jurkat T cells. Conclusion: Our results suggest that UC-MSCs attenuate ALI via PGE2-dependent reprogramming of macrophages to promote their PD-L1 expression.

Background: Female fertility refers to the capacity to produce oocytes and achieve fertilization and pregnancy, and it is impaired by age, disease, environment and social pressure. However, no effective therapy that restores female reproductive ability has been established. Mesenchymal Stromal Cells (MSCs) exhibit multilineage differentiation potential and have attracted considerable attention as a tool for restoring female fertility. Methods: This study used human umbilical cord-MSCs (Huc-MSCs) to restore fertility in aging female mice and mice with chemotherapy-induced damage through the rescue of ovarian function and reconstruction of the fallopian tubes and uterus. In our study, two mouse models were generated: aging mice (35 weeks of age) and mice with chemotherapy-induced damage. Results: The effect of MSCs on the ovaries, fallopian tubes and uterus was evaluated by analyzing gonadal hormone levels and by performing morphological and statistical analyses. The levels of estradiol (E2) and follicle-stimulating hormone (FSH) exhibited significant recovery after Huc-MSC transplantation in both aging mice and chemotherapy-treated mice. Huc-MSC treatment also increased the number of primordial, developing and preovulatory follicles in the ovaries of mice. Moreover, MSCs were shown to rescue the morphology of the fallopian tubes and uterus through mechanisms such as cilia regeneration in the fallopian tubes and reformation of glands and endometrial tissue in the uterus. Conclusion: Huc-MSCs may represent an effective treatment for restoring female fertility through recovery from chemotherapy-induced damage and rescue of female reproductive organs from the effects of aging.

Objects. Human umbilical cord Wharton jelly cells (HUCWJCs) treatment has been proven to be a useful treatment approach for various inflammatory diseases. This study investigated the therapeutic effect and mechanism of HUCWJCs on D-galactose-induced osteoporosis in mice. Methods. Sixteen male mice were randomly divided into 4 groups: control (ordinary feeding), D-gal (D-galactose) group, D-gal + MSC (human umbilical cord Wharton jelly cells), and D-gal + MSC-TNFα groups. Except for the control group (fed with same amount of saline solution), other mice received gastric feeding of 250 mg/kg D-galactose every day for 8 weeks. TNFα (10 ng/mL for 24 h) cocultured or noncocultured HUCWJCs (5 × 105) were suspended in 0.1 ml of sterile PBS and injected into tail veins every other week in D-gal + MSC-TNFα and D-gal + MSC groups, respectively, and only 0.1 ml of sterile PBS for control and D-gal groups. The bone mass was detected by qPCR, ELISA, microcomputed tomography (μCT), and hematoxylin-eosin staining. Proliferation, apoptosis, and differentiation of periosteal-derived osteoblasts (POB) were assessed. Transwell assay and scratch healing were performed to detect POB migration and invasion ability. The effect of HUCWJCs on POB signaling pathway expression was evaluated by immunoblotting. Results. The malondialdehyde (MDA) in serum was higher and superoxide dismutase (SOD) was lower in the D-gal group compared to the other groups ( p < 0.05 ). Mice in D-gal group showed significantly decreased bone mass when compared to the control group, while HUCWJCs treatment partially rescued the phenotype, as demonstrated by μCT and histology ( p < 0.05 ). Mechanically, HUCWJCs treatment partially promoted proliferation and migration and decreased apoptosis of POB induced by oxidative stress via activating the mitogen-activated protein kinase (MAPK) signaling pathway. Conclusion. HUCWJCs can prevent the progression of osteoporosis by inhibiting oxidative stress, which may act by regulating osteoblasts fate through the MAPK signaling pathway.

We investigated umbilical cord serum microRNA (miRNA) profiles to identify biomarkers of a risk for obesity later in life. Participating children were divided into high- and low-risk groups of obesity based on the timing of adiposity rebound and the body mass index (BMI) at 5 years and randomly selected from each group for this study. 3D-Gene® Human miRNA Oligo Chip was performed using cord serum in five children of both groups. The most relevant miRNAs were confirmed in 33 children of the groups using the TaqMan® microRNA assay. We detected five cord serum miRNAs differentially expressed in children at high risk of obesity compared with the levels in children at low risk, namely, miR-516-3p and miR-130a-3p with increased levels and miR-1260b, miR-4709-3p, and miR194-3p with decreased levels. This study provides the first identification of altered umbilical cord serum miRNAs in childhood obesity.

Angiomyxoma of the umbilical cord is a rare benign vascular malformation with potential for fetal morbidity and mortality. Gross and histologic features of this lesion are identical to those described as “hemangioma,” however “angiomyxoma” is a preferable term as current practice restricts the term “hemangioma” to infantile capillary proliferations that express glucose transporter 1. Here we describe the case of an umbilical cord angiomyxoma with associated pseudocysts diagnosed after delivery at 33 weeks. It presented as a heterogeneous-appearing mass near the fetal cord insertion and mimicked serious fetal anomalies throughout gestation. We found fetal MRI helpful for monitoring this lesion, narrowing the differential, and informing management. Proximity to the fetal end of the cord and uncertainty about diagnosis also required surgical resection of the mass after delivery with umbilicoplasty.

Background Scientists have been facing numerous challenges in the development of an effective therapeutic strategy for the treatment of COVID-19 pneumonia. Several studies have suggested that improving patient immunity and reducing lung injury induced by SARS-CoV-2 may be effective for treating patients with COVID-19. Methods A pilot trial of nebulization therapy with exosomes of mesenchymal stem cells (MSCs) was performed on seven patients with COVID-19 pneumonia. Exosomes secreted from MSCs were collected and purified using multiple ultrafiltration steps. All patients were treated with nebulization of MSC-derived exosomes, and primary safety and efficacy outcomes were evaluated. Results Our clinical study demonstrated that nebulization of MSC-derived exosomes is a novel method that might be utilized in the treatment of COVID-19 pneumonia. Nebulization of MSC-derived exosomes did not induce acute allergic or secondary allergic reactions but did promote the absorption of pulmonary lesions and reduce the duration of hospitalization for mild cases of COVID-19 pneumonia. Conclusions Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial. Trial Registration Chinese Clinical Trial Registry, ChiCTR2000030261. Registered on 26 February 2020. Graphical Abstract

Multiple pregnancy is associated with high perinatal mortality and morbidity. Abnormal cord insertions more common in twin pregnancies compared to singleton pregnancies and velamentous cord insertion is related with poor pregnancy outcomes. There is no definition of velamentous cord insertion into the intertwine membrane between two fetuses in the literature.In our single-center cross-sectional study, monochorionic-diamniotic and dichorionic-diamniotic twins who were admitted to our clinic between 18 + 0 and 23 + 6 weeks of pregnancy were enrolled in this study. We evaluated fetal, placental, and umbilical cord abnormalities in addition to fetal growth restrictions and weight discordance by ultrasonography.Although abnormal cord insertion frequency was significantly higher in monochorionic twins (p = 0.003), intertwin membrane cord insertion could only occur in dichorionic twins. In cases with cord insertion anomaly; FGR and weight discordance was observed more frequently (p 0.001 and p = 0.003, respectively). Weight discordance, the presence of abnormal cord insertion and abnormal UAD were found as statistically significant predictors of FGR (p 0.001, p = 0.021, and p 0.001, respectively).Intertwin membrane insertion is a novel umbilical cord insertion abnormality. The presence of abnormal umbilical cord insertion is a risk factor for poor pregnancy outcomes in twin pregnancies.

Umbilical cord rupture (UCR) in utero is a very rare and critical emergency that can cause fetal death within minutes. A 38-year-old nulliparous woman was admitted at 39 weeks in labour. Sudden watery vaginal discharge and bleeding with a rapid drop in the fetal heart rate to 60 beats/min necessitated an emergency caesarean section. A male infant weighing 2632 g was delivered 21 min after the onset of bradycardia; Apgar scores were 0 and 1 at 1 and 5 min, respectively. He was extremely pale; the umbilical arterial blood pH was 6.89 and haemoglobin was 9.0 g/dL. The umbilical cord had a velamentous insertion and was lacerated, with haemorrhage in the outer layer of an umbilical artery close to the placental end. The presentation was typical of UCR: vaginal bleeding following the rupture of membranes. Prompt diagnosis of UCR and termination of pregnancy are essential for fetal survival.

Analysis of several parameters is required for adequate quality control in umbilical cord blood units (UCBU) when used for therapeutic purposes.To optimize colony-forming units (CFU) from clonogenic cultures and to detect the human papillomavirus (HPV) genome in UCBU.One hundred and forty-one umbilical cord blood (UCB), segment or CFU samples from UCBU clonogenic cultures were included. DNA extraction, quantification and endogenous GAPDH gene PCR amplification were carried out. Subsequently, HPV L1 gene was detected using the MY09/MY11 and GP5/GP6+ oligonucleotides. PCR products were analyzed with electrophoresis in agarose gel. CFU-extracted purified DNA was analyzed by electrophoresis in agarose gel, as well as some DNAs, using the sequence-specific priming technique.CFU-extracted DNA concentration was higher in comparison with that of UCB (p = 0.0041) and that of the segment (p0.0001), as well as that of UCB in comparison with that of the segment (p0.0001). All samples were positive for GAPDH amplification and negative for MY09/MY/11 and GP5/GP6+.Cryopreserved UCBUs were HPV-negative. Obtaining CFU DNA from clonogenic cultures with high concentrations and purity is feasible.Se requiere analizar diversos parámetros para el control de calidad adecuado de las unidades de sangre de cordón umbilical (USCU) cuando se utilizan con fines terapéuticos.Optimizar las unidades formadoras de colonias (UFC) de cultivos clonogénicos y detectar el genoma del virus del papiloma humano (VPH) en USCU.Se incluyeron 141 muestras de sangre de cordón umbilical (SCU), de segmento y de UFC de cultivos clonogénicos de USCU. Se realizó extracción de ADN, cuantificación y amplificación por PCR del gen endógeno GAPDH. Se detectó el gen L1 del VPH con los oligonucleótidos MY09/MY11 y GP5/GP6+; los productos de PCR se migraron en electroforesis de agarosa. El ADN purificado de las UFC se analizó mediante electroforesis de agarosa y algunos ADN, con la técnica sequence specific priming.La concentración de ADN extraído de UFC fue superior comparada con la de SCU (p = 0.0041) y la de segmento (p0.0001); así como la de SCU comparada con la de segmento (p0.0001). Todas las muestras fueron positivas para la amplificación de GAPDH y negativas para MY09/MY11 y GP5/GP6+.Las USCU criopreservadas fueron VPH netativas; además, es factible obtener ADN en altas concentraciones y con alta pureza a partir de UFC de los cultivos clonogénicos.