Multipotent mesenchymal stromal cells (MSC) have been widely explored for cell-based therapy of immune-mediated, inflammatory, and degenerative diseases, due to their immunosuppressive, immunomodulatory, and regenerative potentials. Preclinical studies and clinical trials have demonstrated promising therapeutic results although these have been somewhat limited. Aspects such as low in vivo MSC survival in inhospitable disease microenvironments, requirements for ex vivo cell overexpansion prior to infusions, intrinsic differences between MSC and different sources and donors, variability of culturing protocols, and potency assays to evaluate MSC products have been described as limitations in the field. In recent years, priming approaches to empower MSC have been investigated, thereby generating cellular products with improved potential for different clinical applications. Herein, we review the current priming approaches that aim to increase MSC therapeutic efficacy. Priming with cytokines and growth factors, hypoxia, pharmacological drugs, biomaterials, and different culture conditions, as well as other diverse molecules, are revised from current and future perspectives.

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Priming approaches to improve the efficacy of mesenchymal stromal cell-based therapies.

Development of novel and effective therapeutics for treating various cancers is probably the most congested and challenging enterprise of pharmaceutical companies. Diverse drugs targeting malignant and nonmalignant cells receive clinical approval each year from the FDA. Targeting cancer cells and nonmalignant cells unavoidably changes the tumor microenvironment, and cellular and molecular components relentlessly alter in response to drugs. Cancer cells often reprogram their metabolic pathways to adapt to environmental challenges and facilitate survival, proliferation, and metastasis. While cancer cells' dependence on glycolysis for energy production is well studied, the roles of adipocytes and lipid metabolic reprogramming in supporting cancer growth, metastasis, and drug responses are less understood. This Review focuses on emerging mechanisms involving adipocytes and lipid metabolism in altering the response to cancer treatment. In particular, we discuss mechanisms underlying cancer-associated adipocytes and lipid metabolic reprogramming in cancer drug resistance.

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Adipocyte and lipid metabolism in cancer drug resistance.

Cell migration is a pervasive process in many biology systems and involves protrusive forces generated by actin polymerization, myosin dependent contractile forces, and force transmission between the cell and the substrate through adhesion sites. Here we develop a computational model for cell motion that uses the phase-field method to solve for the moving boundary with physical membrane properties. It includes a reaction-diffusion model for the actin-myosin machinery and discrete adhesion sites which can be in a “gripping” or “slipping” mode and integrates the adhesion dynamics with the dynamics of the actin filaments, modeled as a viscous network. To test this model, we apply it to fish keratocytes, fast moving cells that maintain their morphology, and show that we are able to reproduce recent experimental results on actin flow and stress patterns. Furthermore, we explore the phase diagram of cell motility by varying myosin II activity and adhesion strength. Our model suggests that the pattern of the actin flow inside the cell, the cell velocity, and the cell morphology are determined by the integration of actin polymerization, myosin contraction, adhesion forces, and membrane forces.

http://absimage.aps.org/image/MAR14/MWS_MAR14-2013-000482.pdf

Coupling actin flow, adhesion, and morphology in a computational cell motility model

Until the late-twentieth century, primary anatomical sciences education was relatively unenhanced by advanced technology and dependent on the mainstays of printed textbooks, chalkboard- and photographic projection-based classroom lectures, and cadaver dissection laboratories But over the past three decades, diffusion of innovations in computer technology transformed the practices of anatomical education and research, along with other aspects of work and daily life Increasing adoption of first-generation personal computers (PCs) in the 1980s paved the way for the first practical educational applications, and visionary anatomists foresaw the usefulness of computers for teaching While early computers lacked high-resolution graphics capabilities and interactive user interfaces, applications with video discs demonstrated the practicality of programming digital multimedia linking descriptive text with anatomical imaging Desktop publishing established that computers could be used for producing enhanced lecture notes, and commercial presentation software made it possible to give lectures using anatomical and medical imaging, as well as animations Concurrently, computer processing supported the deployment of medical imaging modalities, including computed tomography, magnetic resonance imaging, and ultrasound, that were subsequently integrated into anatomy instruction Following its public birth in the mid-1990s, the World Wide Web became the ubiquitous multimedia networking technology underlying the conduct of contemporary education and research Digital video, structural simulations, and mobile devices have been more recently applied to education Progressive implementation of computer-based learning methods interacted with waves of ongoing curricular change, and such technologies have been deemed crucial for continuing medical education reforms, providing new challenges and opportunities for anatomical sciences educators Anat Sci Educ 9: 583-602 © 2016 American Association of Anatomists

From chalkboard, slides, and paper to e-learning: How computing technologies have transformed anatomical sciences education

Immunomodulation by mesenchymal stem cells and clinical experience

Environmental physical cues determine the lineage specification of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) have the capacity to differentiate into multiple lineages including osteogenic and adipogenic lineages. An increasing number of studies have indicated that lineage commitment by MSCs is influenced by actin remodeling. Moreover, actin has roles in determining cell shape, nuclear shape, cell spreading, and cell stiffness, which eventually affect cell differentiation. Osteogenic differentiation is promoted in MSCs that exhibit a large spreading area, increased matrix stiffness, higher levels of actin polymerization, and higher density of stress fibers, whereas adipogenic differentiation is prevalent in MSCs with disrupted actin networks. In addition, the mechanical properties of F-actin empower cells to sense and transduce mechanical stimuli, which are also reported to influence differentiation. Various biomaterials, mechanical, and chemical interventions along with pathogen-induced actin alteration in the form of polymerization and depolymerization in MSC differentiation were studied recently. This review will cover the role of actin and its modifications through the use of different methods in inducing osteogenic and adipogenic differentiation.

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A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells.

The anatomical basis for the concept of meridians in traditional Chinese medicine (TCM) has not been resolved. This paper reviews the evidence supporting a relationship between acupuncture points/meridians and fascia. The reviewed evidence supports the view that the human body's fascia network may be the physical substrate represented by the meridians of TCM. Specifically, this hypothesis is supported by anatomical observations of body scan data demonstrating that the fascia network resembles the theoretical meridian system in salient ways, as well as physiological, histological, and clinical observations. This view represents a theoretical basis and means for applying modern biomedical research to examining TCM principles and therapies, and it favors a holistic approach to diagnosis and treatment.

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Review of Evidence Suggesting That the Fascia Network Could Be the Anatomical Basis for Acupoints and Meridians in the Human Body

The Visible Human Projects, which were launched in the United States, have also been developed in Korea and China during the past decade. This article includes the new trials to promote a variety of their applications. In a Korean laboratory, whole bodies of two cadavers were serially sectioned (Visible Korean), while two Chinese institutes have sectioned nine cadavers (Chinese Visible Human and Virtual Chinese Human). For acquiring sectioned images and stereoscopic models of better quality, appropriate cadavers were chosen; equipments and techniques for embedding, sectioning, photography, and computer processing were continuously improved in the two countries. To facilitate the research, Korean and Chinese scientists have visited each other. The sectioned images with thinner intervals (0.2 mm or less) and higher resolution were obtained. From the advanced data, the segmented images of comprehensive structures were prepared to construct three-dimensional models. Then, cross-sectional images and models were offered for medical education and clinical practice such as electronic anatomy atlas and virtual lumbar puncture. Every project has its strengths and weaknesses with regard to the image data; users in the world can choose the project that best suits their needs.

The Visible Human Projects in Korea and China with improved images and diverse applications

Adipose-derived stem cells (ASCs) that show multidifferentiation and anti-immune rejection capacities have been widely used in plastic and reconstructive surgery. Previous studies have indicated that mechanical and biophysical interactions between cells and their surrounding environment regulate essential processes, such as growth, survival, and differentiation, and the cytoskeleton system plays an important role in the mechanotransduction. However, the role of mechanical force in the determination of lineage fate is still unclear. Human ASCs (hASCs) were obtained from three different donors by liposuction. Adipogenesis and osteogenesis were determined by Oil Red O and Alizarin Red staining, respectively. The mRNA levels of the cytoskeleton system, PPARγ, and C/EBPα were determined by real-time polymerase chain reaction (RT-PCR). The level of cytoskeleton, PPARγ, and C/EBPα protein levels were measured by Western blotting. The morphology of the cytoskeleton system during adipogenesis was observed with confocal microscopy. hASCs were transfected with a SUN2-specific shRNA to knockdown sun2, and a nontargeting shRNA was used as a control. We found that disrupting the physiological balance between the cytoskeleton and the linker of the nucleoskeleton and cytoskeleton (LINC) complex (especially SUN2) could impact the adipogenesis of hASCs in vitro. Microtubule (MT) depolymerization with nocodazole (which interferes with the polymerization of MTs) increased the expression of SUN2 and PPARγ, while taxol (an inhibitor of MT disassembly) showed the opposite results. Meanwhile, hASCs with sun2 knockdown overexpressed MTs and decreased PPARγ expression, thereby inhibiting the adipogenesis. Furthermore, knockdown of sun2 changed the structure of perinuclear MTs. We demonstrated the presence of cross-talk between MT and SUN2, and this cross-talk plays a critical role in the rebalance of the mechanical environment and is involved in the regulation of PPARγ transport during adipogenic differentiation of hASCs.

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Cross-talk between microtubules and the linker of nucleoskeleton complex plays a critical role in the adipogenesis of human adipose-derived stem cells.

Jingxing Dai

Papers

Environmental physical cues determine the lineage specification of mesenchymal stem cells.

A glance on the role of actin in osteogenic and adipogenic differentiation of mesenchymal stem cells.

Review of Evidence Suggesting That the Fascia Network Could Be the Anatomical Basis for Acupoints and Meridians in the Human Body

The Visible Human Projects in Korea and China with improved images and diverse applications

Cross-talk between microtubules and the linker of nucleoskeleton complex plays a critical role in the adipogenesis of human adipose-derived stem cells.