Human stem cells from adult sources have been shown, in our laboratory and others, to promote the repair of damaged tissues. Different populations of stem cells contribute to the regeneration of muscle, neural tissue, liver, heart, and vasculature, although the mechanisms by which they accomplish this are still not well understood. We and others have shown that stem cells home to hypoxic and/or inflamed areas, and release bioactive factors that can suppress the local immune system, enhance angiogenesis, inhibit fibrosis and apoptosis, and stimulate recruitment, retention, mitosis and differentiation of endogenous tissue-residing stem cells. These trophic effects are distinct from the direct differentiation of stem cells into the tissue to be regenerated. To actually rebuild a non-hematopoietic tissue, the differentiated progeny of embryonic or induced pluripotent stem cells will be required. We have focused on improving rodent models in which to examine human stem cell-mediated disease correction and tissue repair, focusing primarily on liver regeneration and hypoxic tissue models of peripheral vascular disease and cardiac ischemia. Most recently we are studying mesenchymal stem cell–mediated repair of neural damage. We are interested in the mechanisms by which stem cells of different types and origins home preferentially into areas of tissue damage, and we seek to improve the robustness. To track cells into the damaged tissues in vivo, we have labeled them with fluorophore – conjugated iron oxide nanoparticles and have used novel mouse models that facilitate human cell detection. We have also used 19F magnetic resonance imaging for stem cell tracking with multiple unique perfluorocarbon nanobeacons, human/murine centromeric FISH, immunohistochemistry and quantitative PCR. Using these technologies, we have shown that human stem cells migrate from the bloodstream randomly and in moderate numbers throughout all tissues examined in cases of chronic disease or following sublethal irradiation, but that in instances of acute damage, the homing is more vigorous and specific to the site of damage. Pre-culture in hypoxia dramatically alters the phenotype and migratory characteristics of human mesenchymal stem cells. We are applying this knowledge to tissue repair strategies, to allow enhanced numbers of stem cells to migrate to the areas of hypoxic damage, to exert trophic effects that initiate revascularization and cascades of repair.

The beta decay of Mg-33 (N 21) presented in this Letter reveals intruder configurations in both the parent and the daughter nucleus. The lowest excited states in the N 20 daughter nucleus, 33Al, are found to have nearly 2p - 2h intruder configuration, thus extending the "island of inversion"' beyond Mg. The allowed direct beta-decay branch to the 5/2(+) ground state of the daughter nucleus Al-33 implies positive parity for the ground state of the parent Mg-33, contrary to an earlier suggestion of negative parity from a g-factor measurement. An admixture of 1p-1h and 3p-3h configurations is proposed for the ground state of Mg-33 to explain all of the experimental observables.

The beta decay of 33Mg (N=21) presented in this Letter reveals intruder configurations in both the parent and the daughter nucleus. The lowest excited states in the N=20 daughter nucleus, 33Al, are found to have nearly 2p-2h intruder configuration, thus extending the "island of inversion" beyond Mg. The allowed direct beta-decay branch to the 5/2{+} ground state of the daughter nucleus 33Al implies positive parity for the ground state of the parent 33Mg, contrary to an earlier suggestion of negative parity from a g-factor measurement. An admixture of 1p-1h and 3p-3h configurations is proposed for the ground state of 33Mg to explain all of the experimental observables.

The low energy level structure of N = 20 Mg-32 obtained via beta-delayed gamma spectroscopy is reported. The level structure of Mg-32 is found to be completely dominated by intruders. An inversion between the 1p-1h and 3p-3h states is observed for the negative parity states, similar to the 0p-0h and 2p-2h inversion for the positive parity states in these N similar to 20 nuclei. The intruder excited states, both positive and negative parity, are reasonably explained by Monte Carlo shell model calculations, which suggest a shrinking N = 20 shell gap with decreasing Z.

Received 25 September 2007DOI:https://doi.org/10.1103/PhysRevC.76.049902©2007 American Physical Society

The beta decay of the exotic 30Ne (N=20) is reported. For the first time, the low-energy level structure of the N=19, 30Na (Tz = 4), is obtained from beta-delayed gamma spectroscopy using fragment-beta-gamma-gamma coincidences. The level structure clearly displays "inversion", i.e., intruder states with mainly 2p2h configurations displacing the normal states to higher excitation energies. The good agreement in excitation energies and the weak and electromagnetic decay patterns with Monte Carlo Shell Model calculations with the SDPF-M interaction in the sdpf valence space illustrates the small d3/2 - f7/2 shell gap. The relative position of the "normal dominant" and "intruder dominant" excited states provides valuable information to understand better the N=20 shell gap.

Genetic modification of human embryonic stem cells (hESCs) is an important tool for understanding and influencing their biologic properties. At the present time, lentiviral vectors pseudotyped with the vesicular stomatitis virus G protein (VSV-G) have been most effective for stable gene transfer to hESCs. However, they also efficiently transduce murine embryonic fibroblasts (MEF), used to support the undifferentiated state of many commonly used hESC lines. Transduction of both the MEF as well as hESCs complicates analyses of gene transfer and expression. We made lentiviral vectors pseudotyped with envelope glycoproteins from retroviruses that have been shown to have more restricted transduction ranges and evaluated their specificity. Lentiviral vectors pseudotyped by the envelopes from either the gibbon ape leukemia virus (GALV) or the RD114 feline endogenous virus (RD114) specifically transduced hESCs to similar extents as VSV-G pseudotyped vectors, but did not transduce MEF. In addition, gene modfication by these pseudotyped lentiviral vectors was stably maintained throughout differentiation of hESCs in vitro. These pseudotyped lentiviral vectors may be valuable tools for efficient, specific and stable gene modification of hESCs.