Monday, January 21, 2013

Stem Cells, Duchenne Muscular Dystrophy (DCM) & Cardiomyopathies

Transplanting Aorta-derived mesoangioblasts (ADMs) to Prevent ADM Related Cardiomyopathy-ADMs can be induced to express cardiac markers, including Nkx2.5, cardiac tropomyosin, cardiac troponin I, and -actinin, and adopt cardiomyocyte morphology. Transplantation of ADMs into the heart of mdx/utrn−/− mice prior to development of DCM prevented onset of cardiomyopathy, as measured by echocardiography, and resulted in significantly higher CD31 expression, consistent with new vessel formation. Dystrophin-positive cardiomyocytes and increased proliferation of endogenous Nestin cardiac stem cells (Neuromics' Chicken Polyclonal Nestin antibody was used as a marker to determine presence of these cells) were detected in ADM-injected heart: JU LAN CHUN, ROBERT O’BRIEN, MIN HO SONG, BLAKE F.WONDRASCH, SUZANNE E. BERRY.Injection of Vessel-Derived Stem Cells Prevents Dilated Cardiomyopathy and Promotes Angiogenesis and Endogenous Cardiac Stem Cell Proliferation in mdx/utrn−/− but Not Aged mdx Mouse Models for Duchenne Muscular Dystrophy. STEM CELLS TRANSLATIONAL MEDICINE 2013;2:000–000.
Figure 6. Nestin and cardiac myocytes in ADM-transplanted mdx/utrn / heart. Fluorescent microscopy was used to visualize nestin interstitial and striated cells in the heart. (A): There were significantly fewer nestin interstitial stem cells in ADM-injected (dko/ADMs, n 5) mdx/utrn / heart in comparison with age-matched wild-type heart injected with saline (WT/HBSS, n 4). p values were obtained using Student’s t test. No difference was observed between WT/HBSS versus dKO/HBSS (p .0538) or dKO/HBSS versus dKO/ADMs (p .3843). (B–F): Nestin striated cells (green, indicated by white arrows) were observed in four of five mdx/utrn / hearts transplanted with ADMs. (C): A cluster of nestin striated cells (green, indicated by white arrows) and surrounding tissue containing nestin interstitial stem cells (also green, indicated by yellow arrowheads). (D–F): The same cluster of nestin cells (green) shown in (C), at higher magnification, expressed cardiac troponin I (red [E, F]). (G): Some nestin striated cells were also observed in one of four mdx/utrn / hearts injected with saline. (H): Nestin striated cells were not present in saline-injected wild-type heart. Abbreviations: ADM, aorta-derived mesoangioblast; cTpI, cardiac troponin I; DAPI, 4 ,6-diamidino-2-phenylindole; dKO, double knockout mdx/utrn / ; HBSS, Hanks’ balanced saline solution; WT, wild-type.

Conclusion: ADMs delay or prevent development of DCM in dystrophin-deficient heart, but timing of stem cell transplantation may be critical for achieving benefit with cell therapy in DMDcardiac muscle.
Stem Cell Research Reagents.

No comments: