Physical And Chemical Modification On Red Blood Cells

Blood transfusion is a crucial component of modern meidcal care. Problems of blood supply and rare blood group matching have puzzled clinical transfusion and blood service. These problems are more serious during sudden accidents and social activities. Furthermore, for chronically transfused patients allosensitization occurs with high frequency and appropriate rare blood group donors cannot be quickly found. Consequently, it is very important to develop immunocamouflaged red blood cells (RBCs) and inexhaustible blood substitutes.Hematopoietic stem cells (HSC) are being increasingly for treatment of malignant and nonmalignant disorders. The key problem is the total absolute number of these cells limited its applications and how to expand ex vivo in order to increase their therapeutic potential. Xenograft animal models provide suitable stem cell assays and the ideal environment for HSC growth. In this study, we discussed the possibility of maintaining and expanding human HSC in pig xenografted animal models.Previous studies have showen that methoxypolyethylene glycol (mPEG) can mask RBC surface antigens and attenuate RBC antigenicity, and thus agglutination with antibodies is decreased. Our experiments indicated that, the mPEG derivatives both mPEG-BTC (20kD) and mPEG-SPA (20kD) gave comparable findings; modified with 1.0mmol/L mPEG-BTC could effectively camouflage MNSs Duffy Kidd rare blood group antigens; in addition, two-phase partitioning system could efficiently separate unmodified and modified RBC; mPEG and cell membrane bound hard. Compared with control RBC mPEG-RBC could live normally in recipient mouse; mPEG was metabolized in vivo safely and no cumulation.Using animal blood to transfusion, xenotransfusion, could overcome concerns ofsupply and disease transmission. Xenoantigens are the major barrier to successful transfusion, which include a-Gal antigen (Galal-3Galpl-4GlcNAc-R and Galal -3Galpl-4GlcNAcpl-3Galpl-4Glc-R ) and non-aGal antigen. Correspondingly, xenoreactive natural antibodies (XNA) are ubiquitous in humans and old-world monkeys, we examined the effect of reducing animal erythrocyte antigenicity by removal of a-Gal epitopes and masking of non-aGal antigen on RBC membrane, which treated by recombinant coffee bean a-galactosidase (rCa-GalE) degestion combined with mPEG-BTC camouflage. The results showed that of the 4 catties (porcine, bovine, equine, and ovine) the best robust RBC is bovine RBC; the combination of the two treatments was most effective on eliminating of bovine RBC xenoantigens; the treated RBC's morphology, structures, functions, and deformabiliry were maintained; clinically used cross-match tests between treated bovine RBCs and human sera demonstrated increased compatibility.In this study, we tried to transplant human cord blood hematopoietic stem/progenitor cells(HSC/HPC) into preimmune fetal and neonatal pigs by utero and umbilical cord transplantation approach. The types of transplanted human HSC/HPC were CD34+ cells, cord blood monocytes, and mPEG modified cord blood monocytes respectively. The results showed that a proportion of human cells existed in peripheral blood in all transplantation manners and lasted till 60 days when engrfted cord blood monocytes to neonatal pig, except dissected uterus technique. It suggests that developed human/pig chimaera is possible.