Mesenchymal Stem/Stromal Cells: HIGH-RESOLUTION MASS-SPECTROMETRY-BASED PROTEOMICS AND FUNCTIONAL VALIDATION REVEALED DISTINCT THERAPEUTIC CAPABILITIES RELATED TO DIFFERENT PRIMING STRATEGIES IN MESENCHYMAL STROMAL/STEM CELLS: POTENTIAL IMPLICATIONS FOR THEIR CLINICAL USE

V. Miceli, S.D. Scilabra, M. Calligaris, G. Zito,R. Busà,A. Gallo,M. Bulati,P. Conaldi

Cytotherapy(2023)

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摘要
Isotope dilution W whole-rock data, coupled with data for other trace elements in 42 peridotite xenoliths from Tariat (Mongolia), Yangyuan and Hannuoba (China), and Letlhakane (Botswana) are used to constrain the W abundance and behavior in the continental lithospheric mantle. Tungsten concentrations are >11 ng g−1, even in the most depleted peridotites, and higher than the W abundance estimate of the bulk silicate Earth (BSE) in all but one sample. Combined W-Th-U systematics reveal fractionation of W from Th and U with increasing degree of melt depletion, while incompatible element-enriched samples display no such fractionation. Integrated melt reactions and degrees of melt depletion are estimated based on either residual Th or residual Yb abundances for each sample, relative to a BSE precursor. This allows modelling of different partial melting scenarios that consider maximized trace element retention (Th-based model; where measured Th contents are decoupled from Al2O3 contents) or correction for metasomatic trace element contributions (Yb-based model; where measured Yb contents are well-coupled with Al2O3 contents). Modelled residual W concentrations reveal W excesses of 11–19 ng g−1, even when correcting for metasomatic W contributions. Combined with available in situ trace element mineral data for the rock-forming silicates and spinel, which all display W abundances much higher than expected, these findings suggest that either (i) W is less incompatible than previously thought, or that (ii) the peridotites experienced W metasomatism after the last melt depletion event with subsequent re-equilibration. The latter is unlikely, as similar geochemical patterns are observed for oceanic lithospheric mantle based on published data, requiring such W metasomatism to be a global phenomenon. We thus conclude that W is not as incompatible as Th and U during upper mantle melting and potential W-Th-U fractionation mechanisms are examined to explain near-constant W/Th and W/U in mantle melts. We propose revised W concentrations for the BSE of 27 ± 16 ng g−1 to 31 ± 14 ng g−1 and for the depleted mantle of 22 ± 13 ng g−1.
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关键词
Mesenchymal stromal/stem cells, Priming, Advanced Therapy Medicinal Products
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