Relative effects of GAL+ and GALlow/- porcine hematopoietic cells on primate platelet aggregation and endothelial cell activation: implications for the induction of mixed hematopoietic chimerism in the pig-to-primate model.

BACKGROUND

The induction of porcine hematopoietic cell chimerism in preconditioned baboons has been hampered by the development of thrombotic microangiopathy. As pigs that lack expression of Gal alpha 1,3 Gal (Gal) may become available in the near future, we have explored the effects of porcine hematopoietic cells that express low or no Gal (Gal(low/-)) on baboon platelet aggregation and on human umbilical vein endothelial cell (HUVEC) activation.

METHODS

Porcine mobilized peripheral blood progenitor cells (PBPC; Gal(+)) and bone marrow mononuclear cells (BM; Gal(+) or Gal(low/-)) were investigated for their potential to (i) induce aggregation of baboon platelets, and (ii) to activate endothelial cells as measured by increased expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin on HUVEC. alpha-Galactosidase-treated PBPC were also investigated for their effect on platelet aggregation.

RESULTS

Gal(+) PBPC and Gal(+) BM cells (10(7)) induced aggregation of baboon platelets by 42 and 31%, respectively, whereas Gal(low/-) BM cells did not induce any platelet aggregation. alpha-Galactosidase-treated PBPC induced less platelet aggregation than untreated PBPC. Gal(+) PBPC and Gal(+) BM cells (10(7)) increased expression of VCAM-1, ICAM-1 and E-selectin on HUVEC, whereas Gal(low/-) BM cells did not.

CONCLUSIONS

In contrast to Gal(+) PBPC or BM, Gal(low/-) BM cells do not induce aggregation of baboon platelets or activate HUVEC. The induction of tolerance through mixed hematopoietic cell chimerism may be facilitated when alpha-galactosyltransferase-knockout pigs become available.