We here present an immunologic head-to-head comparison between human umbilical cord lining mesenchymal stem cells (clMSCs) and adult bone marrow MSCs (bmMSCs) from patients >65 years of age. clMSCs had significantly lower HLA class I expression, higher production of tolerogenic TGF-β and IL-10, and showed significantly faster proliferation. In vitro activation of allogeneic lymphocytes and xenogeneic in vivo immune activation was significantly stronger with bmMSCs, whereas immune recognition of clMSCs was significantly weaker. Thus, bmMSCs were more quickly rejected in immunocompetent mice. IFN-γ at 25 ng/ml increased both immunogenicity by upregulation of HLA class I/ HLA-DR expression and tolerogenicity by increasing intracellular HLA-G and surface HLA-E expression, augmenting TGF-β and IL-10 release, and inducing indoleamine 2,3-dioxygenase (IDO) expression. Higher concentrations of IFN-γ (>50 ng/ml) further enhanced the immunosuppressive phenotype of clMSCs, more strongly downregulating HLA-DR expression and further increasing IDO production (at 500 ng/ml). The net functional immunosuppressive efficacy of MSCs was tested in mixed lymphocyte cultures. Although both clMSCs and bmMSCs significantly reduced in vitro immune activation, clMSCs were significantly more effective than bmMSCs. The veto function of both MSC lines was enhanced in escalating IFN-γ environments. In conclusion, clMSCs show a more beneficial immunogeneic profile and stronger overall immunosuppressive potential than aged bmMSCs.

The use of human stem cells (SCs) is a promising novel approach for the treatment of many diseases and injuries. Umbilical cord and amniotic membrane represent good sources for SCs, because they are abundant sources and there are less ethical issues unlike embryonic SCs. We aimed to isolate and characterize adult SCs from the subamnion region of the umbilical cord/amniotic membrane. Because mesenchymal stem cells (MSCs) are thought to show less immunogenicity, we first focused on the characterization of MSCs. Significant expression of typical SC-specific markers, such as SSEA-4, Oct-4, and Nanog was observed. Subamniotic MSCs did not lose the expression of Oct-4 and Nanog after freeze-thawing. Cell surface expression of MSC markers (CD73 and CD105) was confirmed by flow cytometry, and cells also differentiated into adipogenic, osteogenic, and chondrogenic lineages. On the other hand, typical embryonic SC-specific markers were not expressed and the cells also did not grow in soft agar. Thus, the subamniotic MSCs are distinct from embryonic SCs and do not show tumorigenicity in vitro. The cord lining membrane (subamniotic) MSCs isolated by our method maintain typical characteristics of MSCs in vitro, but also showed several specific features.

Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis during the wound healing process. As epithelial-mesenchymal interactions have been shown to regulate a plethora of genes in wound healing, we hypothesized that these interactions might have a role in modulating VEGF expression and angiogenesis. A two chamber co-culture model was used, wherein normal and keloid keratinocytes and fibroblasts were physically separated by membrane inserts while allowing cytokine diffusion. Cell lysates obtained from keratinocytes co-cultured with fibroblasts demonstrated increased expression of VEGF. An enzyme-linked immunosorbent assay (ELISA) showed significant increase in VEGF expression in co-culture conditioned media compared with controls. Additionally, the conditioned medium from keloid keratinocyte and fibroblast co-cultures increased proliferation and formation of complex three-dimensional capillary-like structures in human umbilical vein endothelial cells, emphasising the importance of epithelial-mesenchymal interactions in the angiogenic process. Immunostaining of keloid tissue localized VEGF in the basal layer of the epidermis and also demonstrated higher blood vessel density than normal skin. Keloid tissue extract also demonstrated increased expression of VEGF compared with normal skin. It is likely that epidermal VEGF exerts significant paracrine control over the dynamics and expression profile of underlying dermal fibroblasts. Addition of the inhibitors WP631, mitoxantrone, and Rapamycin to keloid keratinocyte and fibroblast co-cultures, downregulated secreted VEGF expression in a dose-dependent manner, suggesting therapeutic potential for these compounds in the treatment of keloid scars.

Social networks affect many aspects of life, including the spread of diseases, the diffusion of information, the workers' productivity, and consumers' behavior. Little is known, however, about how these networks form and change. Estimating causal effects and mechanisms that drive social network formation and dynamics is challenging because of the complexity of engineering social relations in a controlled environment, endogeneity between network structure and individual characteristics, and the lack of timeresolved data about individuals' behavior. We leverage data from a sample of 1.5 million college students on Facebook, who wrote more than 630 million messages and 590 million posts over 4 years, to design a long-term natural experiment of friendship formation and social dynamics in the aftermath of a natural disaster. The analysis shows that affected individuals are more likely to strengthen interactions, while maintaining the same number of friends as unaffected individuals. Our findings suggest that the formation of social relationships may serve as a coping mechanism to deal with high-stress situations and build resilience in communities.social networks | natural disasters | causal inference | natural experiment | propensity score matching S ocial networks affect many aspects of life, including the spread of diseases (1), access to resources and information (2), the diffusion of knowledge (3, 4), productivity and stability of organizations (5, 6), and job prospects (7,8). In this paper, we conceptualize a natural experiment † by taking advantage of the well-defined local impact of a hurricane to gain a quantitative understanding of how these networks form and evolve. Our analysis provides insights into how to leverage social dynamics for affecting outcomes of interest, such as how to design policies that can aid rescue and recovery efforts or influence behavior and the economy.Establishing causal relationships in social network formation and dynamics has historically been difficult to study because of endogeneity between network structure and individual characteristics, and the cost of obtaining long time-series about individuals ' behavior (16, 17). In addition, large-scale randomized experiments are often not feasible because of the complexity of engineering social relations in a controlled environment, and the multitude of incentives that influence human behavior (18)(19)(20), and often because of privacy and IRB related issues (e.g., see refs. 21 and 22). Recent research tackle these challenges by developing behavioral models of network formation (23) that can support what-if analyses, and by using automated services such as Amazon Mechanical Turk (aws.amazon.com/documentation/ mturk) to carry out randomized human-subjects experiments of social dynamics in artificial environments, at scale (24-26). Related literature focuses on incentives, aiming at separating influence from selection effects, a task for which negative results exist in general (27, 28), using randomized experiments (29-32) and strategie...

Mesenchymal stromal cells (MSCs) have been isolated from many tissues, including gestational tissue. To date, a study comparing the properties and suitability of these cells in cell-based therapies is lacking. In this study, we compared the phenotype, proliferation rate, migration, immunogenicity, and immunomodulatory capabilities of human MSCs derived from umbilical cord lining (CL-MSCs), umbilical cord blood (CB-MSCs), placenta (P-MSCs), and Wharton's jelly (WJ-MSCs). Differences were noted in differentiation, proliferation, and migration, with CL-MSCs showing the highest proliferation and migration rates resulting in prolonged survival in immunodeficient mice. Moreover, CL-MSCs showed a prolongation in survival in xenogeneic BALB/c mice, which was attributed to their ability to dampen TH1 and TH2 responses. Weaker human cellular immune responses were detected against CL-MSCs and P-MSCs, which were correlated with their lower HLA I expression. Furthermore, HLA II was upregulated less substantially by CL-MSCs and CB-MSCs after IFN-γ stimulation. MSC types did not differ in indolamine 2,3-dioxygenase (IDO) expression after IFN-γ stimulation. Despite their lower IDO, HLA-G, and TGF-β1 expression, only CL-MSCs were able to reduce the release of IFN-γ by lymphocytes in a mixed lymphocyte reaction. In summary, CL-MSCs showed the best characteristics for cell-based strategies, as they are hypo-immunogenic and show high proliferation and migration rates. In addition, these studies show for the first time that although immunomodulatory molecules HLA-G, HLA-E, and TGF-β play an important role in MSC immune evasion, basal and induced HLA expression seems to be decisive in determining the immunogenicity of MSCs.

Burns are a major problem in many developing countries. Eupolin ointment is a topical agent used in the treatment of soft-tissue wounds and burns in Vietnam and is made from an aqueous extract of the leaves of Chromolaena odorata (formerly Eupatorium odoratum). Clinical studies using this extract have shown antimicrobial and anticoagulation effects as well as the promotion of tissue remodeling in the wound healing process. However, the mechanism by which this agent affects cells involved in the wound healing process is unknown. In our research, fibroblasts and endothelial cells, two cell types that play a crucial role in wound healing, were used to investigate some of the effects of Eupolin extract in vitro. Cell growth was estimated by a colorimetric assay at different time intervals. Enhanced growth of fibroblasts and endothelial cells was found at concentrations of 10 microg/ml and 100 microg/ml of Eupolin extract. This was particularly evident in medium supplemented with only 0.5% fetal calf serum where the cells were quiescent. Toxicity of the extract to fibroblasts was observed at 250 microg/ml in Dulbecco's modified Eagle's medium/0.5% fetal calf serum, but there was no significant damage at this dose to the endothelial cells. The results of the study demonstrated that Eupolin extract increased fibroblast and endothelial cell growth, and this could explain in part the beneficial clinical effects that have been observed.

Abstract:The umbilical cord tissue has gained attention in recent years as a source of multipotent cells. Due to its widespread availability, the umbilical cord may be an excellent alternative source of cells for regenerative medicine. Anatomically, umbilical cord tissue is constituted of several different parts, and, accordingly, immunostaining of cord tissue sections revealed differential distribution of several markers and extracellular matrix, distinguishing the various layers. Wharton's jelly is the major component filling the inner part of the umbilical cord tissue, and it has been commonly used as a source of obtaining multipotent cells from umbilical cord. We recently reported isolating mesenchymal stem cells from cord lining membrane (sub-amnion). However, because of several anatomically distinct zones found in the umbilical cord, isolated multipotent cells sometimes show heterogeneity. In addition, differences in isolation technique may lead to further variation. In this review, we discuss the similarities and differences between the cells derived from each sub-region, including sub-amnion as recently reported by us. We further explore the specific features and advantages/disadvantages of Wharton's jelly and the other sub-compartments in the umbilical cord tissue as sources of stem cells/multipotent cells.

The cellular-level effects of low/high frequency oscillating magnetic field on excitable cells such as neurons are well established. In contrast, the effects of a homogeneous, static magnetic field (SMF) on Central Nervous System (CNS) glial cells are less investigated. Here, we have developed an in vitro SMF stimulation set-up to investigate the genomic effects of SMF exposure on oligodendrocyte differentiation and neurotrophic factors secretion. Human oligodendrocytes precursor cells (OPCs) were stimulated with moderate intensity SMF (0.3 T) for a period of two weeks (two hours/day). The differential gene expression of cell activity marker (c-fos), early OPC (Olig1, Olig2. Sox10), and mature oligodendrocyte markers (CNP, MBP) were quantified. The enhanced myelination capacity of the SMF stimulated oligodendrocytes was validated in a dorsal root ganglion microfluidics chamber platform. Additionally, the effects of SMF on the gene expression and secretion of neurotrophic factors- BDNF and NT3 was quantified. We also report that SMF stimulation increases the intracellular calcium influx in OPCs as well as the gene expression of L-type channel subunits-CaV1.2 and CaV1.3. Our findings emphasize the ability of glial cells such as OPCs to positively respond to moderate intensity SMF stimulation by exhibiting enhanced differentiation, functionality as well as neurotrophic factor release.