A set of 11 genes, termed the common rejection module, predicts acute graft rejection in solid organ transplant patients and may help to identify novel drug targets in transplantation.

Organs are composites of tissue types with diverse developmental origins, and they rely on distinct stem and progenitor cells to meet physiological demands for cellular production and homeostasis. How diverse stem cell activity is coordinated within organs is not well understood. Here we describe a lineage-restricted, self-renewing common skeletal progenitor (bone, cartilage, stromal progenitor; BCSP) isolated from limb bones and bone marrow tissue of fetal, neonatal, and adult mice. The BCSP clonally produces chondrocytes (cartilage-forming) and osteogenic (bone-forming) cells and at least three subsets of stromal cells that exhibit differential expression of cell surface markers, including CD105 (or endoglin), Thy1 [or CD90 (cluster of differentiation 90)], and 6C3 [ENPEP glutamyl aminopeptidase (aminopeptidase A)]. These three stromal subsets exhibit differential capacities to support hematopoietic (blood-forming) stem and progenitor cells. Although the 6C3-expressing subset demonstrates functional stem cell niche activity by maintaining primitive hematopoietic stem cell (HSC) renewal in vitro, the other stromal populations promote HSC differentiation to more committed lines of hematopoiesis, such as the B-cell lineage. Gene expression analysis and microscopic studies further reveal a microenvironment in which CD105-, Thy1-, and 6C3-expressing marrow stroma collaborate to provide cytokine signaling to HSCs and more committed hematopoietic progenitors. As a result, within the context of bone as a blood-forming organ, the BCSP plays a critical role in supporting hematopoiesis through its generation of diverse osteogenic and hematopoietic-promoting stroma, including HSC supportive 6C3(+) niche cells.endochondral ossification | lymphopoiesis

Background Although stem cell therapy has provided a promising treatment for myocardial infarction, the low survival of the transplanted cells in the infarcted myocardium is possibly a primary reason for failure of long-term improvement. Therefore, the development of novel pro-survival strategies to boost stem cell survival will be of significant benefit to this field. Method and Results Cardiac progenitor cells (CPCs) were isolated from transgenic mice which constitutively express firefly luciferase and green fluorescent protein. The CPCs were transduced with individual lentivirus carrying the precursor of miR-21, miR-24, and miR-221, a cocktail of these 3 miRNA precursors, or GFP as control. After challenge in serum free medium, CPCs treated with the 3 miRNA cocktail showed significantly higher viability compared to untreated CPCs. Following intramuscular and intramyocardial injections, in vivo bioluminescence imaging (BLI) showed that miRNA cocktail-treated CPCs survived significantly longer after transplantation. Following left anterior descending artery ligation, miRNA cocktail-treated CPCs boosts the therapeutic efficacy in terms of functional recovery. Histological analysis confirmed increased myocardial wall thickness and CPC engraftment in the myocardium with miRNA cocktail. Finally, we used bioinformatics analysis and experimental validation assays to show that Bim, a critical apoptotic activator, is an important target gene of the miRNA cocktail, which collectively can bind to the 3’UTR region of Bim and suppress its expression. Conclusion We have demonstrated that a miRNA pro-survival cocktail (miR-21, miR-24, and miR-221) can improve the engraftment of transplanted cardiac progenitor cells and therapeutic efficacy for treatment of ischemic heart disease.

There is an emerging hypothesis that exposure to cadmium (Cd), mercury (Hg), lead (Pb), and selenium (Se) in utero and early childhood could have long-term health consequences. However, there are sparse data on early life exposures to these elements in US populations, particularly in urban minority samples. This study measured levels of Cd, Hg, Pb, and Se in 50 paired maternal, umbilical cord, and postnatal blood samples from the Boston Birth Cohort (BBC). Maternal exposure to Cd, Hg, Pb, and Se was 100% detectable in red blood cells (RBCs), and there was a high degree of maternal–fetal transfer of Hg, Pb, and Se. In particular, we found that Hg levels in cord RBCs were 1.5 times higher than those found in the mothers. This study also investigated changes in concentrations of Cd, Hg, Pb, and Se during the first few years of life. We found decreased levels of Hg and Se but elevated Pb levels in early childhood. Finally, this study investigated the association between metal burden and preterm birth and low birthweight. We found significantly higher levels of Hg in maternal and cord plasma and RBCs in preterm or low birthweight births, compared with term or normal birthweight births. In conclusion, this study showed that maternal exposure to these elements was widespread in the BBC, and maternal–fetal transfer was a major source of early life exposure to Hg, Pb, and Se. Our results also suggest that RBCs are better than plasma at reflecting the trans-placental transfer of Hg, Pb, and Se from the mother to the fetus. Our study findings remain to be confirmed in larger studies, and the implications for early screening and interventions of preconception and pregnant mothers and newborns warrant further investigation.

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A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2 + / CD13 + /KDR + /PDGFRα + cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2 + cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2 + /CD13 + /KDR + /PDGFRα + cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart. engraftment | surface markers | Stem cells | mature cardiomyocytes | clonal analysis

Background-Interleukin-17 , which is predominantly produced by T helper 17 cells distinct from T helper 1 or T helper 2 cells, participates in the pathogenesis of infectious, autoimmune, and allergic disorders. However, the precise role in allograft rejection remains uncertain. In the present study, we investigated the role of IL-17 in acute allograft rejection using IL-17-deficient mice. Methods and Results-Donor hearts from FVB mice were heterotopically transplanted into either C57BL/6J-IL-17-deficient (IL-17

Soot particles are the most efficient light absorbing aerosol species in the atmosphere, playing an important role as a driver of global warming. Their climate effects strongly depend on their mixing state, which significantly changes their light absorbing capability and cloud condensation nuclei (CCN) activity. Therefore, knowledge about the mixing state of soot and its aging mechanism becomes an important topic in the atmospheric sciences. <br><br> The size-resolved (30–320 nm diameter) mixing state of soot particles in polluted megacity air was measured at a suburban site (Yufa) during the CAREBeijing 2006 campaign in Beijing, using a volatility tandem differential mobility analyzer (VTDMA). Particles in this size range with non-volatile residuals at 300 &deg;C were considered to be soot particles. On average, the number fraction of internally mixed soot in total soot particles (<i>F</i>_in), decreased from 0.80 to 0.57 when initial <i>D</i>_p increased from 30 to 320 nm. Further analysis reveals that: (1) <i>F</i>_in was well correlated with the aerosol hygroscopic mixing state measured by a CCN counter. More externally mixed soot particles were observed when particles showed more heterogeneous features with regard to hygroscopicity. (2) <i>F</i>_in had pronounced diurnal cycles. For particles in the accumulation mode (<i>D</i>_p at 100–320 nm), largest <i>F</i>_in were observed at noon time, with "apparent" turnover rates (<i>k</i>_{ex &rarr; in}) up to 7.8% h⁻¹. (3) <i>F</i>_in was subject to competing effects of both aging and emissions. While aging increases <i>F</i>_in by converting externally mixed soot particles into internally mixed ones, emissions tend to reduce <i>F</i>_in by emitting more fresh and externally mixed soot particles. Similar competing effects were also found with air mass age indicators. (4) Under the estimated emission intensities, actual turnover rates of soot (<i>k</i>_{ex &rarr; in}) up to 20% h⁻¹ were derived, which showed a pronounced diurnal cycle peaking around noon time. This result confirms that (soot) particles are undergoing fast aging/coating with the existing high levels of condensable vapors in the megacity Beijing. (5) Diurnal cycles of <i>F</i>_in were different between Aitken and accumulation mode particles, which could be explained by the faster growth of smaller Aitken mode particles into larger size bins. <br><br> To improve the <i>F</i>_in prediction in regional/global models, we suggest parameterizing <i&g...