Microchimerism in bone marrow–derived CD34+ cells of patients after liver transplantation

Abstract

Lymphoid and dendritic cells of donor origin can be detected in the recipient several years after a solid organ transplantation. This phenomenon is termed microchimerism and could play a role in the induction of tolerance. The fate of other hematopoietic cells transferred by liver transplantation, in particular of stem and progenitor cells, is unknown. For this reason, we studied peripheral blood and bone marrow samples of 12 patients who had received a liver transplant from an HLA-DR mismatched donor. Eight patients were long-term survivors between 2.8 and 10.1 years after allografting. CD34+ cells from bone marrow were highly enriched with the use of a 2-step method, and a nested polymerase chain reaction was applied to detect donor cells on the basis of allelic differences of the HLA-DRB1 gene. Rigorous controls with DRB1 specificities equal to the donor and host were included. In 5 of 8 long-term liver recipients, donor-specific CD34+ cells could be detected in bone marrow. Microchimerism in the CD34+ cell fraction did not correlate to the chimeric status in peripheral blood. In conclusion, our results demonstrate a frequent microchimerism among bone marrow–derived CD34+ cells after liver transplantation. The functional role of this phenomenon still needs to be defined.

It's moving day: factors affecting peripheral blood stem mobilization and strategies for improvement

“…Despite the success of PBSC transplantation, the exact mechanisms involved in PBSC mobilization and homing are not yet clear. In adults, small amounts of PBSC are present in the peripheral blood (PB) during steady state haematopoiesis, as has been known for 40 years (Goodman & Hodgson, 1962; Dorie et al , 1979; Fruehauf et al , 1995), suggesting a continuous migration and exchange of haematopoietic stem cells between the bone marrow (BM) and other organs, such as the liver and spleen (Starzl et al , 1996; Nierhoff et al, 2000). This model is strongly supported by experiments in which parabiotic mice were surgically conjoined and shared a common circulation (Wright et al, 2001).…”

Hematopoietic stem cells: can old cells learn new tricks?

“…We have shown that after liver transplantation, donor-specific CD34 ϩ cells could be detected in the recipient's BM [55]. In a recent report, Körbling et al [56] provided indications that stem cells derived from peripheral blood could differentiate into mature hepatocytes and epithelial cells of the skin and gastrointestinal tract.…”

“…Long-term repopulating HSC cannot be expanded in vitro without losing developmental potential [1]. Verfaillie and her group [51,52,55] have however recently demonstrated that MAPC could proliferate without obvious senescence under clinically applicable conditions. However, these data need to be confirmed and validated by other groups.…”

Microchimerism, GVHD, and tolerance in solid organ transplantation

“…This was also the conclusion of Miller et al, 57 who suggested that donor cells resident in the recipient marrow might be of primary importance in mediating the immunomodu‐lation necessary for tolerance. It has been shown recently that CD34+ cells of donor origin can be demonstrated in recipient marrow years after liver transplantation 58 …”