Nonhuman primate allogeneic hematopoietic stem cell transplantation by intraosseus vs intravenous injection: Engraftment, donor cell distribution, and mechanistic basis

Abstract

The traditional intravenous (IV) route of administration for hematopoietic stem cell transplantation (HSCT) may result in inefficient placement of donor cells, possibly contributing to suboptimal engraftment and higher risk of graft-vs-host reactions. In order to perform detailed studies of engraftment and donor cell distribution in an animal model with anatomical similarity to man, we performed the first direct homing/engraftment efficiency comparison between intraosseus (IO) and IV HSCT in allogeneic nonhuman primate animal model to assess the utility and mechanism of donor cell homing after IO delivery. Donor bone marrow (BM) cells labeled with PKH26 membrane dye were transplanted to nonmyeloablative-conditioned nonhuman primate animals. Chimerism was confirmed by polymerase chain reaction amplification of donor-specific short tandem repeat locus. Compared to the IO route, IV infusion trapped 2.4- to 4.8-fold more donor cells in peripheral organs, including the lung, heart, spleen, kidney, and liver. IO injection resulting in a 6.2-fold increase in donor cells retained in the BM at the site of injection and a 2.7-fold increase in donor cells retained in distant BM sites. A profile of selected cell adhesion molecules (CAMs) demonstrated that after IO HSCT, more donor cells express CAMs that could facilitate BM homing and redistribution to non-injection-side BM cavities. This change in homing efficiency may be clinically significant because IO transplantation in haploidentical recipients enhanced donor cell engraftment when compared to IV delivery. Our results suggest that IO injection enhances both homing and engraftment in nonhuman primate HSCT.