Human muscle-derived cell populations isolated by differential adhesion rates: Phenotype and contribution to skeletal muscle regeneration in Mdx/SCID mice

Muscle-derived stem cells (MDSCs) isolated from murine skeletal tissue by the preplate method have displayed the capability to commit to the myogenic lineage and regenerate more efficiently than myoblasts in skeletal and cardiac muscle in murine Duchenne Muscular Dystrophy mice (mdx). However, until now, these studies have not been translated to human muscle cells. Here, we describe the isolation, by a preplate technique, of candidate human MDSCs, which exhibit myogenic and regenerative characteristics similar to their murine counterparts. Using the preplate isolation method, we compared cells that adhere faster to the flasks, preplate 2 (PP2), and cells that adhere slower, preplate 6 (PP6). The human PP6 cells express several markers of mesenchymal stem cells and are distinct from human PP2 (a myoblast-like population) based on their expression of CD146 and myogenic markers desmin and CD56. After transplantation to the gastrocnemius muscle of mdx/SCID mice, we observe significantly higher levels of PP6 cells participating in muscle regeneration as compared with the transplantation of PP2 cells. This study supports some previous findings related to mouse preplate cells, and also identifies some differences between mouse and human muscle preplate cells

A role for cell sex in stem cell-mediated skeletal muscle regeneration: Female cells have higher muscle regeneration efficiency

We have shown that muscle-derived stem cells (MDSCs) transplanted into dystrophic (mdx) mice efficiently regenerate skeletal muscle. However, MDSC populations exhibit heterogeneity in marker profiles and variability in regeneration abilities. We show here that cell sex is a variable that considerably influences MDSCs' regeneration abilities. We found that the female MDSCs (F-MDSCs) regenerated skeletal muscle more efficiently. Despite using additional isolation techniques and cell cloning, we could not obtain a male subfraction with a regeneration capacity similar to that of their female counterparts. Rather than being directly hormonal or caused by host immune response, this difference in MDSCs' regeneration potential may arise from innate sex-related differences in the cells' stress responses. In comparison with F-MDSCs, male MDSCs have increased differentiation after exposure to oxidative stress induced by hydrogen peroxide, which may lead to in vivo donor cell depletion, and a proliferative advantage for F-MDSCs that eventually increases muscle regeneration. These findings should persuade researchers to report cell sex, which is a largely unexplored variable, and consider the implications of relying on cells of one sex. © The Rockefeller University Press

Reversal of renal allograft rejection with intravenous methylprednisolone "pulse" therapy,

Intravenous administration of large doses of methylprednisolone sodium succinate was demonstrated to modify rejection in both canine and human renal allografts. One dose of intravenous methylprednisolone 30 mg./kg. administered during acute rejection in dogs resulted in an increase in urine volume and osmolality, and a decrease in serum and urine LDH. In two dogs treated with a single dose and in one dog treated with four consecutive daily doses histologic evidence of reversal of rejection with reduction of cellular infiltrate was achieved. Ninety-two percent of rejections encountered in 100 consecutive human recipients of renal allografts were halted or reversed with intravenous methylprednisolone 30 mg./ kg. given every 48-72 hours to a maximum of three or four doses. No significant side effects were observed either in dogs or humans with this therapy. The mean circulating half-life of intravenous methylprednisolone was determined to be 3.48 +/- 0.7 hours in dogs. Intermittent intravenous administration of methylprednisolone has the potential advantage of being associated with fewer side effects than frequent oral administration and has been shown to be an effective method for modifying rejection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34145/1/0000430.pd

Using e-learning to support international students' dissertation preparation

Purpose: A research paper on the design and implementation of an e-learning resource responding to the globalisation of education. The purpose of this paper is to focus on the challenges presented in learning and teaching on how to support international postgraduate (PG) students undertaking the specific task of a dissertation. Design/methodology/approach: Using findings from 250 PG students, 40 supervisors and two module tutors the research identified the content and language issues faced by students and recognised the need to design an enabler supporting the latter as independent learners and the academic staff delivering support. Findings: The e-learning tool provides an independent learning tool which addresses student concerns relating to the process and content of structuring a dissertation and the function of language. Initial responses have been positive from both staff and students in respect to providing a source of student support and feedback. Originality/value: The research shows how the Dissertation Game Model (DGM), evolved into an e-learning resource supporting student understanding of the content, structure, planning and writing of a dissertation. The e-learning tool focuses on helping international students understand what the generic contents of each chapter of a dissertation should contain and supports them in engaging in research as a transferable skill

Acute Left Atrial Compression after Ventricular Assist Device Placement

Highlights: Pump thrombosis commonly presents with hemolysis and device parameter fluctuations. Left atrial compression presents similarly to pump thrombosis but with no device fluctuations. Reference standard imaging test for ventricular device thrombus is contrast-enhanced CT