A number of adhesion molecules have been implicated in the ability of transplanted hematopoietic stem cells (HSC) to engraft. We investigated whether the expression, or lack thereof, of CD11 a, CD43, CD44, CD49d, CD49e, and CD62L on Sca-1 + lin- cells augments or diminishes the bone marrow (BM) repoputatlng potential of these cells. A total of 103 Sca-l+ lin X+ or Sca-1+ lin X- cells (where X is any of the 6 molecules mentioned above) from B6.Hbbd congenic mice were competitively transplanted along with 3 x 104 C57/BI6 low density BM cells into fethally irradiated C57/BI6 recipients. In the event where all analyzed Sca-1+ Ifrr cells were positive for the expression of a particular adhesion molecule (CD44 and CD49d), Sca-1 Min- cells with dim vs bright expression of CD44 or CD49d were selected. Mice recieving Sca-1+ fcir cells were fully reconstituted with donor-derived cells. Interestingly, chimerism was undetectabte in mice transplanted with Sca-1+lin cells not expressing CD43, CD44, or CD49e, while recipients of Sca-1 + lin cells positive for these markers were 100±0, 67±29, and 976% chimeric, respectively, illustrating the importance of CD43, CD44, and CD49e for engraftment. In contrast, Sca-1+ lin~ cells positive for the expression of CDlia, or CD49d, or CD62L mediated minimal engraftment (range 1 to 21%) compared to the opposing (X~) phenotypes (range 87 to 100%). To determine whether antibodies used for cell sorting interfered with the function of CD11 a, CD49d, or CD62L, the engraftment potential of Sca-1 + lin- cells stained with these antibodies but not sorted was determined, and found to be similar to that achieved with unstained Sca-l+ lin- cells. Cell cycle analyses of all 12 phenotypes examined revealed that a greater percentage of all Sca-1+ lin- X- cells were in GO/G1 than among Sca1+ lin- X+ cells, suggesting that mitotic quiescence, as a single parameter, may not be the most reliable predictor of the engraftment potential of candidate HSC. These studies suggest that CD43, CD44, and CO49e are essential molecules involvedin the homing and anchoring of primitive HPC to the BM microenvironment.
|Original language||English (US)|
|Number of pages||1|
|State||Published - Dec 1 1997|
ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
- Cancer Research