Activation of SMAD independent BMP4 signaling leads to better homing potential and radioprotection. KLS cells were cultured for 5 days in SCF+TPO with BMP4 alone or combined with dorsomorphin or SB203580 and radioprotection and homing ability was evaluated. (A) Survival of mice grafted with 0.1 × 106 KLS cell progeny from different culture conditions after lethal irradiation. Results were analyzed by log-rank test method for trend and expressed as Kaplan-Meier survival curves (n = 10-18, P < .002). (B) KLS cell progeny (1 × 105) from the different cultures were transplanted intravenously in lethally irradiated mice, and BM harvested after 16 hours. Total BM cells (0.1 × 106) were assayed in methylcellulose colony forming assays and CFU-Cs were enumerated. Percentage homing was determined by comparing total CFU-Cs homed with CFU-Cs injected (n = 9, P < .01). (C) Aside from analyzing homed CFCs, in homing assays BM of the recipient mice was analyzed by flow cytometry for donor derived CD45.1 cells. Flow cytometric analysis was extended to quantify the KLS cells homed in the 16 hours after transplantation. Total KLS cells homed in each mice was calculated for different conditions (n = 8, P < .02).
