Intrabone transplantation of CD34+ cells with optimized delivery does not enhance engraftment in a rhesus macaque model.

Intrabone (IB) injection of umbilical cord blood has been proposed as a potential mechanism to improve transplant engraftment and prevent graft failure. However, conventional IB techniques produce low retention of transplanted cells in the marrow. To overcome this barrier, we developed an optimized IB (OIB) injection method using low-volume, computer-controlled slow infusion that promotes cellular retention in the marrow. Here, we compare engraftment of CD34+ cells transplanted in a myeloablative rhesus macaque (RM) model using the OIB method compared with IV delivery. RM CD34+ cells obtained by apheresis were split equally for transduction with lentiviral vectors encoding either green fluorescent protein or yellow fluorescent protein reporters. Following conditioning, one marked autologous population of CD34+ cells was injected directly IB using the OIB method and the other was injected via slow IV push into the same animal (n = 3). Daily flow cytometry of blood quantified the proportion of engrafting cells deriving from each source. Marrow retention was examined using positron emission tomography/computed tomography imaging of 89Zirconium (89Zr)-oxine-labeled CD34+ cells. CD34+ cells injected via the OIB method were retained in the marrow and engrafted in all 3 animals. However, OIB-transplanted progenitor cells did not engraft any faster than those delivered IV and contributed significantly less to hematopoiesis than IV-delivered cells at all time points. Rigorous testing of our OIB delivery system in a competitive RM myeloablative transplant model showed no engraftment advantage over conventional IV infusion. Given the increased complexity and potential risks of IB vs IV approaches, our data do not support IB transplantation as a strategy to improve hematopoietic engraftment.

Ferroportin Q248h, dietary iron, and serum ferritin in community African-Americans with low to high alcohol consumption.

BACKGROUND: Alcohol consumption is associated with increased iron stores. In sub-Saharan Africa, high dietary ionic iron and the ferroportin Q248H allele have also been implicated in iron accumulation. We examined the associations of ferroportin Q248H, alcohol and dietary iron with serum ferritin, aspartate aminotransaminase (AST) and alanine aminotransaminase (ALT) concentrations in African-Americans. METHODS: Inner-city African-Americans (103 men, 40 women) were recruited from the community according to reported ingestion of >4 alcoholic drinks/d or <2/wk. Typical daily heme iron, nonheme iron and alcohol were estimated using University of Hawaii's multiethnic dietary questionnaire. Based on dietary questionnaire estimates we established categories of < versus > or =56 g alcohol/d, equivalent to 4 alcoholic drinks/d assuming 14 g alcohol per drink. RESULTS: Among 143 participants, 77% drank <56 g alcohol/d and 23%> or =56 g/d as estimated by the questionnaire. The prevalence of ferroportin Q248H was 23.3% with alcohol >56 g/d versus 7.5% with lower amounts (p = 0.014). Among subjects with no history of HIV disease, serum ferritin concentration had positive relationships with male gender (p = 0.041), alcohol consumption (p = 0.021) and ALT concentration (p = 0.0001) but not with dietary iron intake or ferroportin Q248H. Serum AST and ALT concentrations had significant positive associations with male gender and hepatitis C seropositivity but not with alcohol or dietary iron intake or ferroportin Q248H. CONCLUSIONS: Our findings suggest a higher prevalence of ferroportin Q248H with greater alcohol consumption, and this higher prevalence raises the possibility that the allele might ameliorate the toxicity of alcohol. Our results suggest that alcohol but not dietary iron contributes to higher body iron stores in African-Americans. Studies with larger numbers of participants are needed to further clarify the relationship of ferroportin Q248H with the toxicity of alcohol consumption.