Accidental ingestion of multiple magnetic beads by children and their impact on the gastrointestinal tract: a single-center study.

OBJECTIVE: In this study, we aimed to enhance the treatment protocols and help understand the harm caused by the accidental ingestion of magnetic beads by children. METHODS: Data were collected from 72 children with multiple gastrointestinal perforations or gastrointestinal obstructions. The 72 pediatric patients were divided into a perforation and a non-perforation group. The data collected for the analysis included the gender, age, medical history, place of residence (rural or urban), and symptoms along with the educational background of the caregiver, the location and quantity of any foreign bodies discovered during the procedure, whether perforation was confirmed during the procedure, and the number of times magnetic beads had been accidentally ingested. RESULTS: The accuracy rate of preoperative gastrointestinal perforation diagnosis via ultrasound was 71%, while that of the upright abdominal X-ray method was only 46%. In terms of symptoms, the risk of perforation was 13.844 and 12.703 times greater in pediatric patients who experienced vomiting and abdominal pain with vomiting and abdominal distension, respectively, compared to patients in an asymptomatic state. There were no statistical differences between the perforation and the non-perforation groups in terms of age, gender, medical history, and the number of magnetic beads ingested (P > 0.05); however, there were statistical differences in terms of white blood cell count (P = 0.048) and c-reactive protein levels (P = 0.033). A total of 56% of cases underwent a laparotomy along with perforation repair and 19% underwent gastroscopy along with laparotomy. All pediatric patients recovered without complications following surgery. CONCLUSION: Abdominal ultrasonography and/or upright abdominal X-ray analyses should be carried out as soon as possible in case of suspicion of accidental ingestion of magnetic beads by children. In most cases, immediate surgical intervention is required. Given the serious consequences of ingesting this type of foreign body, it is essential to inform parents and/or caregivers about the importance of preventing young children from using such products.

Suppression of PTBP1 signaling is responsible for mesenchymal stem cell induced invasion of low malignancy cancer cells.

Mesenchymal stem cells (MSCs) hold great promise as attractive vehicles to deliver therapeutic agents against cancer, while the cross-talk between MSCs and cancer cells remains controversial. Here in an indirect co-culture system we observed that MSCs induced the malignancy transformation of low malignancy cancer cells HT29 and MCF7, whereas MSCs were reprogrammed by high malignancy cancer cells HCT116 and MDA-MB-231 without exerting an obvious influence on them. We further demonstrated that the RNA-binding protein polypyrimidine tract-binding protein 1 (PTBP1) was suppressed in low malignancy cancer cells co-cultured with MSCs. Moreover, shRNA mediated silencing of PTBP1 could promote the invasiveness of HT29 cells while over-expression of PTBP1 attenuate the MSC-induced invasion of HT29 cells. Our results suggested that differential effects of MSCs on the invasion of cancer cells partially corresponded to PTBP1 expression in cancer cells and the maintenance of biological characteristics in MSCs, which insight could provide a theoretical basis for evaluating the safety of MSC application and PTBP1 targeting in cancer treatment.

The effects of different vascular carrier patterns on the angiogenesis and osteogenesis of BMSC-TCP-based tissue-engineered bone in beagle dogs.

Bone repair using tissue-engineered bone (TEB) in a large defect or accompanied by a poor recipient vascular bed is a long-standing challenge. Surgical vascular carrier patterns of vascular bundle (VB) and arteriovenous loop (AV loop) have been shown to improve the vascularization and repair capacity of TEB. However, the effects of these different vascular carrier patterns on angiogenesis and osteogenesis in TEB have never been evaluated. Here, TEB was constructed with bone marrow mesenchymal stem cells (BMSCs) and ß-TCP and prevascularized by the VB or AV loop technique in beagle dogs. The vascularization and bone formation in TEB were quantitatively compared using Microfil perfusion, histological examination and CT and micro-CT analyses. The distribution and constitution of the neovasculature were analysed to determine the underlying mechanism of angiogenesis. The results showed that prevascularized TEB generated bone tissue faster and more homogeneously than untreated TEB. The VB technique was found to strike a better balance between bone regeneration and ß-TCP scaffold degradation than the AV loop strategy, which resulted in more vascularization but less bone yield, due to faster degradation of the ß-TCP scaffold. This study indicates that a suitable triangular relationship, composed of bone regeneration, scaffold degradation and vasculature, is critical to TEB construction. Copyright © 2015 John Wiley & Sons, Ltd.

Influence of Immunogenicity of Allogeneic Bone Marrow Mesenchymal Stem Cells on Bone Tissue Engineering.

Allogeneic bone marrow mesenchymal stem cell (allo-BMSC)-based tissue-engineered bone (TEB) has great potential for bone defect repair. However, the immunogenicities and biological roles of allo-BMSCs are still controversial. In this study, we established an animal model of critical-sized mandibular defect in beagle dogs and compared the repairing effects of allo-BMSC-based TEB with autogenic BMSC (auto-BMSC)-based TEB without the administration of immunosuppressants. During the first 2 weeks postimplantation, a transient immune response in the allo-BMSC group was detected with an increase in proinflammation cytokines TNF-α, IFN-γ, and IL-2, a declination of anti-inflammation cytokine IL-10, and an increase in percentages of CD4(+) and CD8(+) T-cell subsets in peripheral blood. Nevertheless, there was no significant difference in bone union achievement, bone mineral density, and biomechanical properties between the two groups at 12 and 24 weeks postimplantation. Further subcutaneous implantation of allo-BMSCs/scaffold also exhibited the similar transient immune responses in the first 2 weeks postimplantation but followed by a decreased bone formation at 4 and 8 weeks postimplantation. These findings indicate that allo-BMSCs can induce a transient immunoreaction, which may temporally delay the osteogenesis of allo-BMSC/scaffold complex in early stage of in vivo implantation, whereas the long-term engineered bone formation was not affected.

Comparison of immunological characteristics of mesenchymal stem cells derived from human embryonic stem cells and bone marrow.

Mesenchymal stem cell (MSC) has great potential for both regenerative medicine and immunotherapy due to its multipotency and immunomodulatory property. The derivation of MSCs from human tissues involves an invasive procedure and the obtained MSCs often suffer from inconsistent quality. To overcome these issues, the approaches of deriving a highly potent and replenishable population of MSCs from human embryonic stem cells (hESCs) were established. However, few studies compared the immunological characteristics of MSCs derived from hESCs with tissue-derived MSCs or demonstrated differences and the underlying mechanisms. Here, we differentiated H9 hESCs into MSC-like cells (H9-MSCs) through an embryoid body outgrowth method and compared the immunological characteristics of H9-MSCs with bone marrow-derived MSCs (BMSCs). Both sources of derived cells exhibited typical MSC morphologies and surface marker expressions, as well as multipotency to differentiate into osteogenic and adipogenic lineages. A immunological characterization study showed that H9-MSCs and BMSCs had similar immunoprivileged properties without triggering allogeneic lymphocyte proliferation as well as equivalent immunosuppressive effects on T-cell proliferation induced by either cellular or mitogenic stimuli. Flow cytometry analysis revealed a lower expression of human major histocompatability complex class II molecule human lymphocyte antigen (HLA)-DR and a higher expression of coinhibitory molecule B7-H1 in H9-MSCs than in BMSCs. Interferon gamma (IFN-γ) is a proinflammatory cytokine that can induce the expression of HLA class II molecules in many cell types. Our results showed that pretreatment of H9-MSCs and BMSCs with IFN-γ did not change their immunogenicity and immunosuppressive abilities, but increased the difference between H9-MSCs and BMSCs for their expression of HLA-DR. Further detection of expression of molecules involved in IFN-γ signaling pathways suggested that the lower expression of HLA-DR in H9-MSCs could be partially attributed to the lower expression and the less nuclear translocation of its transcriptional factor CIITA. The present study provides evidence that the hESC-derived MSCs share similar immunogenicity and immunosuppressive abilities with BMSCs, but differ in the expression profile of immunological markers and the responsiveness to certain inflammatory cytokines, which suggests that H9-MSCs could be a safe and efficient candidate for MSC treatment in patients with inflammatory disorders.

[Functions of retinoic acid on the biological characteristics of human embryonic stem cells].

OBJECTIVE: To analyze the influence of retinoic acid (RA) on the undifferentiated state and EB formation abilities of human embryonic stem cells. METHODS: The biological characteristics of H9 ESCs after RA treatment were characterized by real-time PCR, MTS proliferation assay and immunofluorescence staining. The expression of three germ layers markers, osteogenic differentiation markers and adipogenic differentiation markers in H9-differentiated embryoid bodies (EBs) with RA treatment were quantified by real time PCR. RESULTS: The proliferation of H9 ESCs in the early logarithmic growth phase was accelerated by RA treatment. In addition, RA induced differentiation of H9 ESC coupled with morphology changes, decreased expression of undifferentiated markers Oct4, Nanog, Sox2 and OCT4 mRNA binding protein Lin28 at mRNA level, and reduced expression of Oct4 at protein level. RA induced formation of cavities in EBs. Real time PCR results showed that the expressions of ectodermal markers: NeuroD1, Noggin; mesodermal markers: Brachyury, Twist and endodermal markers: AFP, GATA-4 were significantly increased (P < 0.05), especially for AFP (P < 0.01), by RA treatment in a dose-dependent manner. In addition, the expression of adipogenic differentiation marker C/EBPalpha was increased while the osteogenic differentiation marker OPN was decreased in EBs after RA treatment for 5 days. CONCLUSIONS: High concentrations of RA induced the loss of stemness in H9 ESCs and excessive differentiation in EBs, and damaged the balance between osteogenic and adipogenic differentiation during early EB differentiation, which may be relevant to the congenital malformations.