Pig hematopoietic cell chimerism in baboons conditioned with a nonmyeloablative regimen and CD154 blockade.
BACKGROUND
In an attempt to induce mixed hematopoietic chimerism and transplantation tolerance in the pig-to-primate model, we have infused high-dose porcine peripheral blood progenitor cells (PBPC) into baboons pretreated with a nonmyeloablative regimen and anti-CD154 monoclonal antibody (mAb).


METHODS
Group 1 baboons (n=2) received a nonmyeloablative regimen including whole body irradiation, pharmacological immunosuppression, porcine hematopoietic growth factors, and immunoadsorption of anti-Galalpha1,3Gal (Gal) antibody before infusion of high doses of PBPC (2.7-4.6x10(10) cells/kg). In group 2 (n=5), cyclosporine was replaced by anti-CD154 mAb. Group 3 (n=3) received the group 1 regimen plus anti-CD154 mAb.


RESULTS
In group 1, pig chimerism was detected in the blood by flow cytometry (FACS) for 5 days (with a maximum of 14%), and continuously up to 13 days by polymerase chain reaction (PCR). In group 2, pig chimerism was detectable for 5 days by FACS (maximum 33%) and continuously up to 28 days by PCR. In group 3, initial pig chimerism was detectable for 5 days by FACS (maximum 73%). Two of three baboons showed reappearance of pig cells on days 11 and 16, respectively. In one, in which no anti-Gal IgG could be detected for 30 days, pig cells were documented in the blood by FACS on days 16-22 (maximum 6% on day 19) and pig colony-forming cells were present in the blood on days 19-33, which we interpreted as evidence of engraftment. Microchimerism was continuous by PCR up to 33 days.


CONCLUSIONS
These results suggest that there is no absolute barrier to pig hematopoietic cell engraftment in primates, and that this may be facilitated if the return of anti-Gal IgG can be prevented.
Bühler
L
L
Transplantation Biology Research Center, Massachusetts General Hospital, MGH East, Building 149-9019, 13th Street, Boston, MA 02129, USA.
Awwad
M
M
Treter
S
S
Chang
Q
Q
Basker
M
M
Alwayn
I P J
IP
Teranishi
K
K
Ericsson
T
T
Moran
K
K
Harper
D
D
Kurilla-Mahon
B
B
Huang
C A
CA
Sackstein
R
R
Sykes
M
M
White-Scharf
M E
ME
Sachs
D H
DH
Down
J D
JD
Cooper
D K
DK
D000818:Animals; D023201:CD40 Ligand / Q000276:immunology*; D002240:Carbohydrate Sequence; D003114:Colony-Forming Units Assay; D006239:Haplotypes / Q000235:genetics; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods; D018380:Hematopoietic Stem Cell Transplantation; D006650:Histocompatibility Testing; D007377:Interleukin-3 / Q000097:blood; D007937:Leukapheresis; D008969:Molecular Sequence Data; D010215:Papio; D013552:Swine; D013556:Swine, Miniature; D018183:Transplantation Chimera; D014183:Transplantation, Heterologous / Q000276:immunology*; D014312:Trisaccharides / Q000097:blood / Q000302:isolation & purification
D016298:Hematopoietic Cell Growth Factors; D007377:Interleukin-3; D014312:Trisaccharides; D023201:CD40 Ligand