Use of T-cell antibodies for donor dosaging in a canine model of in utero hematopoietic stem cell transplantation.
OBJECTIVE
Microchimerism following canine in utero hematopoietic stem cell transplantation (IUHSCT) development of T-cell dosing regimens.


OBJECTIVE
To investigate the use of anti-T-cell antibodies for cell dosing of the donor graft in a canine model of IUHSCT.


METHODS
Canine IUHSCT was performed by ultrasound-guided intraperitoneal injection in days 35-38 of fetal canines with CD34(+) cells at doses of 4.5 x 10(8) to 1.3 x 10(9) cells/kg and T cells (CD3(+) CD5(+)) at doses of 8 x 10(6) to 8.8 x 10(8) cells/kg. Postnatal studies included tissue histology and polymerase chain reaction-based chimerism analysis.


RESULTS
Term survival was 86-100%. Microchimerism (0-2%) was detected in five of eight recipients in multiple tissues. Histopathology revealed no evidence of graft-versus-host disease (GVHD).


CONCLUSIONS
Canine IUHSCT is a useful model to investigate the role of donor T cells in engraftment and GVHD. IUHSCT at early gestational ages with high doses of donor T cells in the graft yields microchimerism in multiple tissues without GVHD.
Petersen
Scott M
SM
Department of Gynecology and Obstetrics, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. speter21@jhmi.edu
Gendelman
Mariya
M
Murphy
Kathleen M
KM
Torbenson
Michael
M
Jones
Richard J
RJ
Althaus
Janyne E
JE
Stetten
Gail
G
Bird
Chris
C
Blakemore
Karin J
KJ
D000818:Animals; D000831:Animals, Newborn; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004285:Dogs; D005260:Female; D046128:Fetal Therapies / Q000379:methods*; D016332:Fetal Tissue Transplantation / Q000276:immunology / Q000379:methods*; D006085:Graft Survival / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008297:Male; D023421:Models, Animal; D011247:Pregnancy; D013601:T-Lymphocytes / Q000276:immunology; D014019:Tissue Donors; D018183:Transplantation Chimera / Q000235:genetics / Q000276:immunology
D000961:Antilymphocyte Serum; D017931:DNA Primers