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Promotion of xenogeneic hematopoietic chimerism in rodents by mononuclear phagocyte depletion
Author(s) -
Cheng J.,
Glaser R. M.,
KrugerGrey H.,
WhiteScharf M. E.,
Cooper D. K. C.,
Thall A. D.
Publication year - 2002
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1034/j.1399-3089.2002.01112.x
Subject(s) - mononuclear phagocyte system , xenotransplantation , haematopoiesis , phagocyte , bone marrow , immunology , biology , peripheral blood mononuclear cell , progenitor cell , macrophage , immune system , stem cell , transplantation , medicine , microbiology and biotechnology , in vitro , biochemistry
Cheng J, Glaser RM, Kruger‐Grey H, White‐Scharf ME, Cooper DKC, Thall AD. Promotion of xenogeneic hematopoietic chimerism in rodents by mononuclear phagocyte depletion. Xenotransplantation 2002; 9: 402–409. © Blackwell Munksgaard, 2002 The successful establishment of tolerance toward pig tissues in primates through hematopoietic progenitor cell engraftment is restricted by the rapid disappearance of these cells in the recipient following infusion. We developed and tested the hypothesis that phagocytes of the reticuloendothelial system are responsible for the rapid clearance of infused pig hematopoietic cells using a mouse model. Mice received non‐myeloablative conditioning and, on various days, were injected with medronate‐encapsulated liposomes (M‐L) or control blank liposomes, followed by the intravenous infusion of miniature swine hematopoietic cells. M‐L were well‐tolerated in mice (n=100) at levels that deplete mononuclear phagocytes. Depletion of mononuclear phagocytes in normal Balb/c mice as well as in severe combined immune deficient mice increased the accumulation of pig hematopoietic cells in the bone marrow (BM) by 10‐fold when measured 24 h after the infusion of the cells. Colony‐forming unit analysis showed an increased accumulation of pig hematopoietic progenitors in the BM of mice that were infused with medronate‐liposomes. We conclude that depletion of mononuclear phagocytes by M‐L has the potential to lower the barrier to the establishment of mixed chimerism and tolerance induction in xenotransplantation.