Recently, we purified from adult murine bone marrow (BM) a population of CXCR4À very small embryonic-like (VSEL) stem cells and hypothesized that similar cells could be also present in human cord blood (CB). Here, we report that by employing a novel two-step isolation procedure -removal of erythrocytes by hypotonic lysis combined with multiparameter sorting -we could isolate from CB a population of human cells that are similar to murine BM-derived VSELs, described previously by us. These CBisolated VSELs (CB-VSEL) are very small (3-5 lm) and highly enriched in a population of CXCR4À CB mononuclear cells, possess large nuclei containing unorganized euchromatin and express nuclear embryonic transcription factors Oct-4 and Nanog and surface embryonic antigen SSEA-4. Further studies are needed to see if human CB-isolated VSELs similar to their murine BM-derived counterparts are endowed with pluripotent stem cell properties.

Objective Assessment of the mobilization of non-hematopoietic very small embryonic-like stem cells (VSEL) in acute myocardial infarction (MI). Background Acute MI induces mobilization of bone marrow stem cells. Recently rare population of VSELs, expressing markers of embryonic pluripotent stem cells (PSC) was identified in adult murine bone marrow and human umbilical cord blood. Methods 31 pts with acute MI and 30 healthy subjects (CTRL) were enrolled. Blood was sampled on admission, after 24 hours and 5 days later. Erythrocytes were lysed and lin-CD45- VSELs were isolated using a live cell sorting system (FACSAria). Results In healthy subjects the median number of circulating VSEL was very low [0.8 (0-1.3] cells/μL. In acute MI VSELs were mobilized early [2.7 (0.2-3.9) cells/μL; p<0.001), and remained elevated after 24 hrs and 5 days [4.7 (0.2-6.4); p<0.003 and 2.6 (0.3-3.6) cells/μL; p<0.03, respectively). The mobilization of VSEL was significantly reduced in patients older than 50 years and with diabetes in comparison to younger and non-diabetic patients. Circulating VSELs were small (7-8 μm) and enriched in mRNA of PSC markers (Oct-4, Nanog), cardiac lineage (GATA-4, Nkx2.5/Csx, MEF2C) and endothelial (VE-cadherin) markers. The presence of PSC markers (Oct-4, SSEA-4) and chemokine receptor CXCR4 in circulating VSELs was confirmed at the protein level by immunofluorescent staining and ImageStream system (ISS) analysis. Conclusion Acute MI induced mobilization of very small embryonic-like stem cells expressing pluripotent markers, early cardiac and endothelial markers and chemokine receptor CXCR4.

Background and Purpose-In a murine model of stroke, we identified a population of very small embryonic-like (VSEL) stem cells (SCs) in adult murine bone marrow that could be mobilized into peripheral blood (PB). This raised the question of whether a similar population of cells is mobilized in human stroke patients. Methods-We evaluated a number of cells that corresponded to VSEL SCs in the PB of 44 stroke patients and 22age-matched controls. After each patient's stroke, PB samples were harvested during the first 24 hours, on day ϩ3, and on day ϩ7 and then compared with normal controls. The circulating human cells with the phenotype of VSEL SCs were evaluated in PB by real-time quantitative polymerase chain reaction, fluorescence-activated cell sorting analysis, and direct immunofluorescence staining. In parallel, we also measured the serum concentration of stromal derived factor-1 by ELISA. Results-In stroke patients, we found an increase in the number of circulating cells expressing SC-associated antigens, such as CD133, CD34, and CXCR4. More important, we found an increase in the number of circulating primitive cells expressing the VSEL phenotype (CXCR4

Increased intestinal permeability has been implicated in various pathologies, has various causes, and can develop during vigorous athletic training. Colostrum bovinum is a natural supplement with a wide range of supposed positive health effects, including reduction of intestine permeability. We assessed influence of colostrum supplementation on intestinal permeability related parameters in a group of 16 athletes during peak training for competition. This double-blind placebo-controlled study compared supplementation for 20 days with 500 mg of colostrum bovinum or placebo (whey). Gut permeability status was assayed by differential absorption of lactulose and mannitol (L/M test) and stool zonulin concentration. Baseline L/M tests found that six of the participants (75%) in the colostrum group had increased intestinal permeability. After supplementation, the test values were within the normal range and were significantly lower than at baseline. The colostrum group Δ values produced by comparing the post-intervention and baseline results were also significantly lower than the placebo group Δ values. The differences in stool zonulin concentration were smaller than those in the L/M test, but were significant when the Δ values due to intervention were compared between the colostrum group and the placebo group. Colostrum bovinum supplementation was safe and effective in decreasing of intestinal permeability in this series of athletes at increased risk of its elevation.