Human Fallopian Tube Mesenchymal Stromal Cells Enhance Bone Regeneration in a Xenotransplanted Model

We have recently reported that human fallopian tubes, which are discarded during surgical procedures of women submitted to sterilization or hysterectomies, are a rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has been previously shown that human mesenchymal stromal cells may be useful in enhancing the speed of bone regeneration. This prompted us to investigate whether htMSCs might be useful for the treatment of osteoporosis or other bone diseases, since they present a pronounced capacity for osteogenic differentiation in vitro. Based on this prior knowledge, our aim was to evaluate, in vivo, the osteogenic capacity of htMSCs to regenerate bone through an already described xenotransplantation model: nonimmunosuppressed (NIS) rats with cranial defects. htMSCs were obtained from five 30–50 years old healthy women and characterized by flow cytometry and for their multipotenciality in vitro capacity (osteogenic, chondrogenic and adipogenic differentiations). Two symmetric full-thickness cranial defects on each parietal region of seven NIS rats were performed. The left side (LS) of six animals was covered with CellCeram (Scaffdex)—a bioabsorbable ceramic composite scaffold that contains 60% hydroxyapatite and 40% β-tricalciumphosphate—only, and the right side (RS) with the CellCeram and htMSCs (106 cells/scaffold). The animals were euthanized at 30, 60 and 90 days postoperatively and cranial tissue samples were taken for histological analysis. After 90 days we observed neobone formation in both sides. However, in animals euthanized 30 and 60 days after the procedure, a mature bone was observed only on the side with htMSCs. PCR and immunofluorescence analysis confirmed the presence of human DNA and thus that human cells were not rejected, which further supports the imunomodulatory property of htMSCs. In conclusion, htMSCs can be used successfully to enhance bone regeneration in vivo, opening a new field for future treatments of osteoporosis and bone reconstruction

Improvement of Cardiac Function in Mouse Myocardial Infarction after Transplantation of Epigenetically-Modified Bone Marrow Progenitor Cells

OBJECTIVE: To study usefulness of bone marrow progenitor cells (BPCs) epigenetically altered by chromatin modifying agents in mediating heart repair after myocardial infarction in mice. METHODS AND RESULTS: We tested the therapeutic efficacy of bone marrow progenitor cells treated with the clinically-used chromatin modifying agents Trichostatin A (TSA, histone deacetylase inhibitor) and 5Aza-2-deoxycytidine (Aza, DNA methylation inhibitor) in a mouse model of acute myocardial infarction (AMI). Treatment of BPCs with Aza and TSA induced expression of pluripotent genes Oct4, Nanog, Sox2, and thereafter culturing these cells in defined cardiac myocyte-conditioned medium resulted in their differentiation into cardiomyocyte progenitors and subsequently into cardiac myocytes. Their transition was deduced by expression of repertoire of markers: Nkx2.5, GATA4, cardiotroponin T, cardiotroponin I, α-sarcomeric actinin, Mef2c and MHC-α. We observed that the modified BPCs had greater AceH3K9 expression and reduced histone deacetylase1 (HDAC1) and lysine-specific demethylase1 (LSD1) expression compared to untreated BPCs, characteristic of epigenetic changes. Intra-myocardial injection of modified BPCs after AMI in mice significantly improved left ventricular function. These changes were ascribed to differentiation of the injected cells into cardiomyocytes and endothelial cells. CONCLUSION: Treatment of BPCs with Aza and TSA converts BPCs into multipotent cells, which can then be differentiated into myocyte progenitors. Transplantation of these modified progenitor cells into infarcted mouse hearts improved left ventricular function secondary to differentiation of cells in the niche into myocytes and endothelial cells

Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response

Aims: The relationship between variants in SLCO1B1 and SLCO2B1 genes and lipid-lowering response to atorvastatin was investigated. Material and Methods: One-hundred-thirty-six unrelated individuals with hypercholesterolemia were selected and treated with atorvastatin (10 mg/day/4 weeks). They were genotyped with a panel of ancestry informative markers for individual African component of ancestry (ACA) estimation by SNaPshot® and SLCO1B1 (c.388A>G, c.463C>A and c.521T>C) and SLCO2B1 (−71T>C) gene polymorphisms were identified by TaqMan® Real-time PCR. Results: Subjects carrying SLCO1B1 c.388GG genotype exhibited significantly high low-density lipoprotein (LDL) cholesterol reduction relative to c.388AA+c.388AG carriers (41 vs. 37%, p = 0.034). Haplotype analysis revealed that homozygous of SLCO1B1*15 (c.521C and c.388G) variant had similar response to statin relative to heterozygous and non-carriers. A multivariate logistic regression analysis confirmed that c.388GG genotype was associated with higher LDL cholesterol reduction in the study population (OR: 3.2, CI95%:1.3–8.0, p < 0.05). Conclusion: SLCO1B1 c.388A>G polymorphism causes significant increase in atorvastatin response and may be an important marker for predicting efficacy of lipid-lowering therapy

Corporate brand representations in B2B companies’ websites

In the business-to-business (B2B) domain, the corporate website is an effective platform for communicating to stakeholders the corporate brand (CB) features, such as personality and values. Despite the growing importance of websites as a primary means for corporate communication, research on the dimensions that companies ought to use relevant for online corporate branding is limited. This study examines the representations of CBs on the websites of B2B companies in two emerging markets—Brazil and India. The study provides insights into how B2B companies operating in these markets are managing their corporate branding. In particular the research establishes dimensions used for the representation of the CB in the company’s website (e.g., CB personality, CB values). In addition, the study investigates whether the representations of CB have an impact on the company’s financial performance. We analyzed Brazilian and Indian B2B companies’ websites, focusing on the pages containing corporate information and/or information about the parent company. The data collection and analysis were developed in 2 stages, entailing a pilot study and a main study. The pilot study aimed at developing and refining the description of the ways companies used for representing their CB in the websites. It further allowed for the testing of the coding procedure. The main study incorporated the final description of the CB dimensions and performance measures based on the stock index data from Bloomberg. The analysis included websites from 158 Indian and 158 Brazilian B2B companies. Findings allow the specification of relevant elements that should be used to express the CB in an online setting. The study proposes that the following dimensions should be considered to express the CB: CB values; CB personality; CB heritage, and company demographics. The study’s context of two emerging economies showed the stability of the dimensions when applied to companies from two different emerging countries. The study further showed a positive impact of the level of CB online expressions on business performance. The research allows drawing managerial recommendations and avenues for future research.</p

The Impact of Entrepreneurial Orientation on Foreign Market Entry:the Roles of Marketing Program Adaptation, Cultural Distance, and Unanticipated Events

Scholars assert that firms with a strong entrepreneurial orientation (EO) should enjoy an advantage in foreign market entry. However, extant theory, particularly the dominant logic and adaptation frameworks, as well as supporting empirical research outside the domain of foreign market entry, suggests that the positive impact of a strong EO on foreign market entry is likely to be situational. Per the dynamic capabilities perspective, the authors first propose that marketing program adaptation (MPA) is a mediator of the EO-foreign market entry relationship. They further propose two moderators of the EO-MPA relationship, both of which are related to foreign market uncertainty: cultural distance (which increases uncertainty but is known prior to entry) and unanticipated events (which increases uncertainty but by definition are not known prior to entry). A study of 245 US MNCs supports the thesis that MPA is strongly related to foreign market entry success and that EO is an important contributor to foreign entry success when cultural distance is high and unanticipated events occur during launch but is less relevant in the opposite scenarios. There are important implications for firms entering foreign markets