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Background aims. We explored the potential therapeutic value of transplanting bone marrow (BM)-derived mesenchymal stromal cells (MSC) into utrophin/dystrophin-deficient double knock-out (dko) mice, a murine model of Duchenne muscular dystrophy. Methods. MSC from male rats were isolated and transplanted into female dko mice via the caudal vein. Behavior and locomotor function were later evaluated, along with the expression of dystrophin and utrophin in the sarcolemma of myofiber tissues. The presence of grafted cells was confirmed via polymerase chain reaction for the sex-determining region of the Y-chromosome. Results. Locomotor activity improved significantly ( P < 0.05) from 5 to 15 weeks after cell transplantation, as measured by traction, rotating rod and running wheel tests. We also found that the expression of dystrophin and utrophin increased significantly ( P < 0.05) and progressively in the sarcolemma from 5 to 15 weeks after transplantation. The median lifespan of mice in the normal group (74.1 weeks) was significantly ( P < 0.001) higher than those in the control (22.0 weeks) and transplantation (35.0 weeks) groups, and the median lifespan of mice in the transplantation group was significantly ( P < 0.001) higher than that in the control group. Conclusions. Results of this study demonstrate that BM MSC have potential value in xenogeneic transplantation therapy for muscular dystrophy. [ABSTRACT FROM AUTHOR]

Abstract  Human mesenchymal stem cells (hMSC) are a population of multipotent cells that can differentiate into osteoblasts, chondrocytes, adipocytes, and other cells. The exact mechanism governing the differentiation of hMSC into osteoblasts remains largely unknown. Here, we analyzed protein expression profiles of undifferentiated as well as osteogenic induced hMSC using 2-D gel electrophoresis (2-DE), mass spectrometry (MS), and peptide mass fingerprinting (PMF) to investigate the early gene expression in osteoblast differentiation. We have generated proteome maps of undifferentiated hMSC and osteogenic induced hMSC on day 3 and day 7. 2-DE revealed 102 spots with at least 2.0-fold changes in expression and 52 differently expressed proteins were successfully identified by MALDI-TOF-MS. These proteins were classified into 7 functional categories: metabolism, signal transduction, transcription, calcium-binding protein, protein degradation, protein folding and others. The expression of some identified proteins was confirmed by further RT-PCR analyses. This study clarifies the global proteome during osteoblast differentiation. Our results will play an important role in better elucidating the underlying molecular mechanism in hMSC differentiation into osteoblasts. [ABSTRACT FROM AUTHOR]

Embryonic stem (ES) cells can differentiate into a variety of specialized cell types when introduced into early embryos (i.e., morulas or blastocysts) of the same species. A question of medical and basic biological importance is whether ES cells of one species can differentiate properly and contribute significantly to chimerism when placed within early embryos of another distantly related species. Here, we address this question using two divergent mammalian model organisms, Apodemus sylvaticus and Mus musculus, whose genomes differ by about 15%. Despite this considerable evolutionary distance, injection of Apodemus ES cells into Mus blastocysts led to viable chimeras bearing extensive Apodemus contributions in all the major organs. Immunostaining showed that Apodemus ES cells had differentiated into a wide range of cell types in the chimeras. These results support the feasibility of deriving a variety of specialized cells or perhaps even complex tissues from ES cells of one species by placing them in the blastocysts of another divergent species. Our data also highlight the remarkable evolutionary conservation of developmental signaling by revealing its compatibility between two rathe distantly related organisms. [ABSTRACT FROM AUTHOR]