Analysis of the Spanish CCR5-∆32 inventory of cord blood units: lower cell counts in homozygous donors.

The possibility to use CCR5-∆32 umbilical cord blood to cure HIV infection in patients in need of a hematopoietic transplant has been suggested. The less stringent HLA compatibility needed in this type of transplant facilitates the search of a suitable donor having the CCR5-∆32 mutation. To achieve an inventory of CCR5-∆32 cord blood units, the 20,236 best cell quality units of the Spanish Registry were genotyped. Furthermore, their CD34+ and total nucleated cells counts, blood type, gender, HLA and donor's geographical and ancestral origin were analyzed. The results showed 130 (0.64%) units homozygous for the deletion, 2,646 (13.08%) heterozygous and 17,460 (86.28%) did not present the mutation. Interestingly, a significant lower amount of CD34+ cells was found in the CCR5-∆32 homozygous units. In addition, a significant association was found among donor's ancestral origin and the mutation, with a higher percentage of CCR5-∆32 units with a European ancestry. In summary, identification of a relatively high number of CCR5-∆32 units is feasible and will facilitate the development of clinical trials for HIV cure in patients requiring hematopoietic transplantation. Further studies are required to understand the significance of lower cell counts within the CCR5-∆32 homozygous group and its clinical impact.

Acellular human heart matrix: A critical step toward whole heart grafts.

The best definitive treatment option for end-stage heart failure currently is transplantation, which is limited by donor availability and immunorejection. Generating an autologous bioartificial heart could overcome these limitations. Here, we have decellularized a human heart, preserving its 3-dimensional architecture and vascularity, and recellularized the decellularized extracellular matrix (dECM). We decellularized 39 human hearts with sodium-dodecyl-sulfate for 4-8 days. Cell removal and architectural integrity were determined anatomically, functionally, and histologically. To assess cytocompatibility, we cultured human cardiac-progenitor cells (hCPC), bone-marrow mesenchymal cells (hMSCs), human endothelial cells (HUVECs), and H9c1 and HL-1 cardiomyocytes in vitro on dECM ventricles up to 21 days. Cell survival, gene expression, organization and/or electrical coupling were analyzed and compared to conventional 2-dimensional cultures. Decellularization removed cells but preserved the 3-dimensional cardiac macro and microstructure and the native vascular network in a perfusable state. Cell survival was observed on dECM for 21 days. hCPCs and hMSCs expressed cardiocyte genes but did not adopt cardiocyte morphology or organization; HUVECs formed a lining of endocardium and vasculature; differentiated cardiomyocytes organized into nascent muscle bundles and displayed mature calcium dynamics and electrical coupling in recellularized dECM. In summary, decellularization of human hearts provides a biocompatible scaffold that retains 3-dimensional architecture and vascularity and that can be recellularized with parenchymal and vascular cells. dECM promotes cardiocyte gene expression in stem cells and organizes existing cardiomyocytes into nascent muscle showing electrical coupling. These findings represent a first step toward manufacturing human heart grafts or matrix components for treating cardiovascular disease.

The Spanish National Transplant Organization (ONT) tumor registry.

BACKGROUND: It is important to know the actual risk of tumor transmission from donor to recipient and the serious consequences for the recipient. Tumor registries can help us to improve our knowledge about this problem. METHODS: We have studied all the donors registered in the Spanish National Transplant Organization from January 1, 1990, to December 31, 2006, and especially the donors with a malignant tumor as well as the recipients who have received an organ from these donors. RESULTS: We found 117 donors with a malignant tumor (5.8 per 1000 donors). One hundred fifty-five recipients were transplanted with an organ from these donors. The average age (SD) of donors with tumor was 53 (17) years. The most frequent cause of death was cerebral stroke in 81 donors. Donors with tumor are older than donors without tumor. The cause of death was cerebral stroke more frequently in donors with tumor than donors without tumor. Twenty-two of the recipients who received an organ from a donor with a tumor are dead. In 7 of these 22 recipients the death was cancer-related. Only 13 of the 100 recipients studied developed a malignant tumor, and only 10 of these tumors were donor-related. CONCLUSIONS: The profile of a donor who could have a tumor was most frequently an elderly person who had died of a cerebral stroke. In our experience, the risk of tumor transmission from donors to recipients is low and depends on the aggressiveness of the donor tumor.

Magnesium metabolism after cardiac surgery in children.

OBJECTIVE: To analyze magnesium metabolism in children after cardiac surgery. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit (PICU) of a university hospital. PATIENTS: A total of 42 children in the perioperative period of cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Determinations of serum magnesium (MgS), ultrafiltrable magnesium (MgU), intraerythrocytic magnesium, urinary magnesium, blood and urinary calcium, phosphorus, sodium, and blood and urinary creatinine were made in the operating room before surgery, at admission to the PICU, at 24 hrs, and at 3 and 5 days after surgery. The relationship with age, sex, diagnosis, type of surgery, arrhythmias, complications, length of stay in the PICU, and mortality was analyzed. MgS and MgU levels decreased after cardiac surgery (MgS before surgery, 0.74 +/- 0.09 mmol/L; MgS at admission to the PICU, 0.66 +/- 0.11 mmol/L; MgU before surgery, 0.56 +/- 0.06 mmol/L; MgU at admission to the PICU, 0.50 +/- 0.07 mmol/L; p <.0001 for both values). At admission to the PICU, 61.5% of the patients had MgS of <0.63 mmol/L, and 47.2% of the patients had an MgU of <0.46 mmol/L. MgS and MgU had increased by 24 hrs and showed further increases over the first 5 days after surgery. There were no significant changes in the intraerythrocytic magnesium levels in the postoperative period. Changes of MgS and MgU were greater after extracorporeal circulation than after closed surgery (p <.001). There was no correlation between MgS, MgU, or intraerythrocytic magnesium and other analytic and clinical parameters. No patient presented arrhythmias and none died. CONCLUSIONS: After cardiac surgery, and particularly after extracorporeal circulation surgery, children present with low MgS and MgU levels at admission to the PICU. MgS and MgU levels increase over the first 5 days after cardiac surgery. No relationship was found between magnesium levels and the postoperative course.