Homing and engraftment potential of Sca-1(+)lin(-) cells fractionated on the basis of adhesion molecule expression and position in cell cycle

Engraftment potential of hematopoietic stem cells (HSCs) is likely to be de pendent an several factors including expression of certain adhesion molecul es (AMs) and degree of mitotic quiescence. The authors investigated the fun ctional properties and engraftment potential of Sca-1(+)lin(-) cells subfra ctianated on the basis of expression, or lack thereof, of CD11a, CD43, CD49 d, CD49e, or CD62L and correlated that expression with cell cycle status an d proliferative potential of engrafting fractions. Donor-derived chimerism in mice receiving CD49e(+) or CD43(+) Sca-1(+)lin(-) cells was greater than that in mice receiving cells lacking these 2 markers, while Sca-1(+)lin(-) cells positive for CD11a and CD62L and bright for CD49d expression mediate d minimal engraftment AM phenotypes enriched for engraftment potential cont ained the majority of high proliferative potential-colony forming cells, lo w proliferative potential-colony forming cells, and cells providing rapid i n vitro expansion, Cell cycle analysis of AM subpopulations revealed that, regardless of their bone marrow repopulating potential, Sca-1(+)lin(-) AM(- ) cells contained a higher percentage of cells in G(0)/G(1) than their AM() counterparts. Interestingly, engrafting phenotypes, regardless of the sta tus of their AM expression, were quicker to exit G(0)/G(1) following in vit ro cytokine stimulation than their opposing phenotypes, When engrafting phe notypes of Sca-1(+)lin(-) AM(+) or AM(-) cells were further fractionated by Hoechst 33342 into G(0)/G(1) or S/G(2)+M, cells providing long-term engraf tment were predominantly contained within the quiescent fraction. These res ults define a theoretical phenotype of a Sca-1(+)lin(-) engrafting cell as one that is mitotically quiescent, CD43(+), CD49e(+), CD11a(-), CD49d(dlm), and CD62L(-). Furthermore, these data suggest that kinetics of in vitro pr oliferation may be a good predictor of engraftment potential of candidate p opulations of HSCs. (Blood, 2000;96: 1380-1387) (C) 2000 by The American So ciety of Hematology.