Vascularized bone marrow transplantation: A new surgical approach using isolated femoral bone/bone marrow.
BACKGROUND
Orthotopic composite tissue (limb) transplantation in rats is a unique model for vascularized bone marrow transplantation because bone marrow cells and bone marrow stroma are transplanted by microsurgical means, thus creating immediate bone marrow space and engraftment. However, it contains a skin component and other musculoskeletal tissues that complicate issues related to tolerance induction.


METHODS
To study only aspects of vascularized bone marrow transplantation, we created a new isolated vascularized bone marrow transplant model in rats. The common iliac (or femoral) artery and vein were microsurgically anastomosed to the recipient abdominal aorta and inferior vena cava in an end-to-side fashion, respectively. Syngeneic male Lewis (RT1(1), n = 20) and allogeneic male BN (RT1(n), n = 10) donors were transplanted to female Lewis recipients. To establish rejection criteria, we examined histopathology and used the polymerase chain reaction (PCR) to assess microchimerism of donor male bone marrow cells in the peripheral blood of female recipients using rat Y chromosome (sex-determining region Y)-specific primers.


RESULTS
All recipients were healthy and remained stable without major complications for up to 300 days posttransplant. Morphologically, syngeneic male Lewis bone marrow showed a near-normal appearance. Allogeneic male BN bone marrow was clearly rejected. Male bone marrow cells were detected by PCR in the peripheral blood of all syngeneic recipients, but not in allogeneic blood specimens.


CONCLUSIONS
A new surgical approach to bone marrow transplantation was established. This consisted of the vascularized femoral bone/bone marrow transplant. Further analyses regarding the ability of vascularized femoral bone marrow transplants to induce systemic transplantation tolerance in adult rats will provide insights into not only various issues of immunology but also the potential clinical application of vascularized bone marrow transplantation.
Suzuki
H
H
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School/Cooper Health System, 3 Cooper Plaza, Suite 411, Camden, New Jersey 08103, USA.
Patel
N
N
Matthews
M
M
DelRossi
A J
AJ
Doolin
E J
EJ
Hewitt
C W
CW
D000818:Animals; D001853:Bone Marrow / Q000098:blood supply* / Q000473:pathology; D016026:Bone Marrow Transplantation; D002455:Cell Division; D002678:Chimera; D005260:Female; D005269:Femur / Q000098:blood supply; D008297:Male; D008833:Microcirculation; D011184:Postoperative Period; D051381:Rats; D011917:Rats, Inbred Lew; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic