Stem cell transplantation, as used clinically, suffers from low retention and engraftment of the transplanted cells. Inspired by the ability of platelets to recruit stem cells to sites of injury on blood vessels, we hypothesized that platelets might enhance the vascular delivery of cardiac stem cells (CSCs) to sites of myocardial infarction injury. Here, we show that CSCs with platelet nanovesicles fused onto their surface membranes express platelet surface markers that are associated with platelet adhesion to injury sites. We also find that the modified CSCs selectively bind collagen-coated surfaces and endothelium-denuded rat aortas, and that in rat and porcine models of acute myocardial infarction the modified CSCs increase retention in the heart and reduce infarct size. Platelet-nanovesicle-fused CSCs thus possess the natural targeting and repairing ability of their parental cell types. This stem cell manipulation approach is fast, straightforward and safe, does not require genetic alteration of the cells, and should be generalizable to multiple cell types.

Cardiovascular disease is the leading cause of mortality in the world. While reperfusion therapy is vital for patient survival post-heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post-ischemic recovery. A platelet-inspired nano-cell (PINC) that incorporates both prostaglandin E2 (PGE 2 )-modified platelet membrane and cardiac stromal cellsecreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct-homing ability of platelet membrane and the overexpression of PGE 2 receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be This article is protected by copyright. All rights reserved. 3 achieved by PINC, which combines the paracrine mechanism of stem cell therapy with the PGE 2 /EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury.

Layering a regenerative polymer scaffold on the surface of the heart, termed as a cardiac patch, has been proven to be effective in preserving cardiac function after myocardial infarction (MI). However, the placement of such a patch on the heart usually needs open-chest surgery, which is traumatic, therefore prevents the translation of this strategy into the clinic. We sought to device a way to apply a cardiac patch by spray painting in situ polymerizable biomaterials onto the heart with a minimally invasive procedure. To prove the concept, we used platelet fibrin gel as the ''paint'' material in a mouse model of MI. The use of the spraying system allowed for placement of a uniform cardiac patch on the heart in a mini-invasive manner without the need for sutures or glue. The spray treatment promoted cardiac repair and attenuated cardiac dysfunction after MI.

BackgroundResident stem and progenitor cells have been identified in the lung over the last decade, but isolation and culture of these cells remains a challenge. Thus, although these lung stem and progenitor cells provide an ideal source for stem-cell based therapy, mesenchymal stem cells (MSCs) remain the most popular cell therapy product for the treatment of lung diseases. Surgical lung biopsies can be the tissue source but such procedures carry a high risk of mortality.MethodsIn this study we demonstrate that therapeutic lung cells, termed “lung spheroid cells” (LSCs) can be generated from minimally invasive transbronchial lung biopsies using a three-dimensional culture technique. The cells were then characterized by flow cytometry and immunohistochemistry. Angiogenic potential was tested by in-vitro HUVEC tube formation assay. In-vivo bio- distribution of LSCs was examined in athymic nude mice after intravenous delivery.ResultsFrom one lung biopsy, we are able to derive >50 million LSC cells at Passage 2. These cells were characterized by flow cytometry and immunohistochemistry and were shown to represent a mixture of lung stem cells and supporting cells. When introduced systemically into nude mice, LSCs were retained primarily in the lungs for up to 21 days.ConclusionHere, for the first time, we demonstrated that direct culture and expansion of human lung progenitor cells from pulmonary tissues, acquired through a minimally invasive biopsy, is possible and straightforward with a three-dimensional culture technique. These cells could be utilized in long-term expansion of lung progenitor cells and as part of the development of cell-based therapies for the treatment of lung diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF).Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-017-0611-0) contains supplementary material, which is available to authorized users.

Idiopathic pulmonary fibrosis is a devastating interstitial lung disease characterized by the relentless deposition of extracellular matrix causing lung distortions and dysfunctions. The prognosis after detection is merely 3-5 years and the only two Food and Drug Administration-approved drugs treat the symptoms, not the disease, and have numerous side effects. Stem cell therapy is a promising treatment strategy for pulmonary fibrosis. Current animal and clinical studies focus on the use of adipose or bone marrow-derived mesenchymal stem cells. We, instead, have established adult lung spheroid cells (LSCs) as an intrinsic source of therapeutic lung stem cells. In the present study, we compared the efficacy and safety of syngeneic and allogeneic LSCs in immunocompetent rats with bleomycin-induced pulmonary inflammation in an effort to mitigate fibrosis development. We found that infusion of allogeneic LSCs reduces the progression of inflammation and fibrotic manifestation and preserves epithelial and endothelial health without eliciting significant immune rejection. Our study sheds light on potential future developments of LSCs as an allogeneic cell therapy for humans with pulmonary fibrosis. STEM CELLS TRANSLATIONAL MEDICINE 2017;9:1905-1916 SIGNIFICANCE STATEMENTWe have demonstrated the safety and efficacy of allogeneic lung spheroid cell (LSC) treatment in attenuating the progression and severity of pulmonary fibrosis, decreasing apoptosis, protecting alveolar structures, and increasing angiogenesis in rats. The use of allogeneic stem cells can potentially change the way we perform cell therapies by allowing for the growth of large quantities of cells from numerous sources, including donated lungs not used for transplantations, surgical discards, and lungs from recently deceased cadavers. Our study demonstrates the potential of allogeneic LSCs as a viable future therapy option for patients suffering from idiopathic pulmonary fibrosis.

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Tamoxifen, a selective estrogen receptor modulator (SERM), has been used for many decades as the "gold standard" adjuvant treatment for patients with hormonereceptor-positive early breast cancer. This drug, when administered for 5 years, reduces the risk for recurrence, contralateral breast cancer (BC) and death. These benefits have been observed up to 15 years and are independent of the patient's age, menopausal status, nodal status, hormonal receptor status, and the use of adjuvant chemotherapy. The optimal duration of tamoxifen in the adjuvant setting has not been established yet, but it has been demonstrated that 5 years are better than shorter treatment while it is still unclear if a prolongation of the treatment for more than 5 years is worthwhile. Tamoxifen is usually well-tolerated, but important adverse events such as endometrial cancer, cerebrovascular accidents and thromboembolic events can occur, and the increase in absolute risk of these adverse events appears to be age-correlated. Colozza et al.administration have shown superimposable results in terms of efficacy with AIs given up-front or in sequence to tamoxifen. AIs seem to give benefits in comparison to placebo if given after 5 years (late switch) of tamoxifen. At the moment, therefore, the treatment decision should be based on individual factors such as risk of relapse, absolute benefit, and comorbidities.

In human resource management, the motivations, expectations, strengths, and weaknesses of employees are important factors in an organization. For these factors, the Millennial is a generation that awaits higher expectations than previous generations. The current problems of leadership traits and styles are not well understood, especially businesses in Vietnam. This study deals with the behavior of the leaders in the place where they are working, Millennial take over the leadership role. The qualitative study aims to understand and explore the key characteristics and styles of Millennial leaders. Interest groups are affected by advanced technology, new perspectives on teamwork, professional requirements among peers, and their management. The topic is of particular interest to researchers as it transforms into a leadership role within the company. The data analysis showed good saturation and supported some key characteristics of Millennial when employees move in to reach out to their leaders. Companies can measure the success of a group through established accountability. For instance, a commitment to positive reinforcement as a primary motivation is the current widespread tendency.