Stable multilineage chimerism across full MHC barriers without graft-versus-host disease following in utero bone marrow transplantation in pigs.
Stable engraftment of hematopoietic progenitors and multilineage chimerism following in utero bone marrow transplantation could be a promising modality for treatment of prenatally diagnosed blood dyscrasias. For treatment of these diseases, stable chimerism in the myeloid and erythroid lineages is important because it is anticipated that donor-derived cells will compensate for defects in these host lineages. In the present study, a preparation of bone marrow that includes fresh, unmanipulated marrow mixed with T-cell-depleted marrow to achieve 1.5% T-cell content, was injected into the intrahepatic portion of the umbilical vein of porcine fetuses at mid-gestation. Donor hematopoietic progenitor cell engraftment was assessed in fetal liver and recipient bone marrow postnatally by donor-specific polymerase chain reaction of colony-forming units. Chimerism was assessed in lymphoid tissues and peripheral blood by flow cytometry. Graft-versus-host disease (GVHD) was assessed by histological analysis of biopsies of skin, bone marrow, liver, and intestine. In this report, we demonstrate that stable multilineage chimerism across a full major histocompatibility complex disparity can be achieved without GVHD through in utero bone marrow transplantation.
Lee
Patricia W
PW
Transplantation Biology Research Center, Massachusestts General Hospital, Boston, MA 02129, USA.
Cina
Robert A
RA
Randolph
Mark A
MA
Goodrich
Jennifer
J
Rowland
Haley
H
Arellano
Ron
R
Kim
Heung Bae
HB
Sachs
David H
DH
Huang
Christene A
CA
D000818:Animals; D016026:Bone Marrow Transplantation; D019070:Cell Lineage / Q000502:physiology*; D005260:Female; D005315:Fetal Diseases / Q000628:therapy; D005865:Gestational Age; D006085:Graft Survival / Q000502:physiology*; D006086:Graft vs Host Disease; D006402:Hematologic Diseases / Q000628:therapy; D006649:Histocompatibility Antigens / Q000502:physiology*; D008212:Lymphocyte Depletion; D011247:Pregnancy; D011296:Prenatal Diagnosis; D034421:Sus scrofa; D013601:T-Lymphocytes; D018183:Transplantation Chimera / Q000502:physiology*; D014599:Uterus
D006649:Histocompatibility Antigens