Use of T-cell antibodies for donor dosaging in a canine model of in utero hematopoietic stem cell transplantation.

Fetal diagnosis and therapy

PubMedID: 17228153

Petersen SM, Gendelman M, Murphy KM, Torbenson M, Jones RJ, Althaus JE, Stetten G, Bird C, Blakemore KJ. Use of T-cell antibodies for donor dosaging in a canine model of in utero hematopoietic stem cell transplantation. Fetal Diagn Ther. 2007;22(3):175-9.
AIM
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.

STUDY DESIGN
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).

CONCLUSION
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.